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GENEMEDICS NUTRITION
Author: Dr. George Shanlikian, M.D. | Last Updated: November 21st, 2024
NAD+ benefits include boosting cellular energy production, enhancing DNA repair, and promoting healthy aging by supporting metabolic functions and reducing oxidative stress. Additionally, NAD+ plays a crucial role in maintaining mitochondrial function and improving cognitive health.
Nicotinamide Adenine Dinucleotide (NAD+) is a coenzyme that is present in each living cell in the body. It is produced from the breakdown of nicotinamide riboside (niagen), an alternative form of vitamin B3 (niacin). NAD+ plays an integral role in energy production and regulation of vital cellular processes such as DNA repair, strengthening cells’ defense systems, conversion of food into a usable form of energy, and regulation of circadian rhythm.
NAD+ converts nutrients into adenosine triphosphate, a compound that provides energy to living cells. Aside from this important function, it works together with various forms of proteins to carry out a wide array of biological processes such as DNA repair, calcium signaling, maintenance of cell energy and chromosomal integrity, and gene expression.
Aging is associated with progressive restriction in the length of telomeres, which are located at chromosome ends. They play an important role in the preservation of chromosome stability. Studies have shown that individuals with longer telomeres have a longer subsequent lifespan. [1-2] Increasing sirtuin activity is known to stabilize telomeres and attenuate age-related telomere shortening. [3] Since NAD+ activates SIRT1, it can help achieve chromosome stability and longer telomeres – all of these mechanisms can increase longevity.
The natural process of aging is associated with a decline in the quality and activity of the “powerhouse of the cell” known as the mitochondria. As the name implies, the mitochondria produce the energy needed to power the cell’s biochemical reactions – everything from the transmission of signals, digestion, muscle function, and other essential bodily processes. Mitochondrial function is a determinant of lifespan and studies show that mitochondrial dysfunction can shorten lifespan. [4-5]
Another mechanism that can help extend lifespan is through the activation of SIRT1 function in the nucleus of cells. Evidence suggests that boosting NAD+ levels through NAD+ supplementation can dramatically ameliorate mitochondrial dysfunction via activation of sirtuin 1 (SIRT1). [6] SIRT1 is an enzyme that plays an integral role in the regulation of proteins involved in cellular metabolism and processes associated with longevity, inflammation, and stress. SIRT1 activation by NAD+ can increase longevity by promoting mitochondrial biogenesis, a cellular process that involves the production of new mitochondria. [7]
A convincing number of evidence suggests that NAD+ can extend lifespan:
While a decline in the function of the mitochondria has been linked with normal aging, this is also associated with a wide array of age-related medical conditions. Evidence suggests that mitochondrial aging contributes to cellular senescence (also known as biological aging), increased inflammation, decreased stem cell activity, reduced healing rate, and a decline in tissue and organ function. [16] Interestingly, NAD+ can reverse age-related mitochondrial dysfunction via SIRT1 activation.
New research found that some of the age-related changes in the structures of the mitochondria can be reversed through NAD+ supplementation. [17] In this study, the administration of NMN (nicotinamide mononucleotide), a molecule that boosts NAD+ levels, via injections in elderly mice reversed age-related mitochondrial deterioration. It was observed that declining NAD+ levels were associated with interruptions in the normal signaling between the cell’s nucleus and mitochondria. Interestingly, raising NAD+ levels restored the communication between these cellular structures.
During the normal process of aging, DNA damage occurs continuously on a massive scale. The age-related DNA damage contributes to cell death and a decline in the function of neurons or nerve cells. This creates a domino effect, causing a gradual decline in a number of bodily functions. NAD+ can mitigate these effects since it is connected to the DNA repair precursor poly adenosine diphosphate-ribose polymerase 1 (PARP 1). PARP 1 consumes NAD+ in the presence of DNA damage in order to promote cell survival. This in turn can help slow down the effects of aging.
Preclinical evidence also shows that boosting NAD+ levels can help mitigate age-related functional decline:
NAD+ plays an integral role in energy production and regulation of vital cellular processes. This includes the conversion of food into a usable form of energy called adenosine triphosphate.
Studies suggest that increased ATP production caused by NAD+ may help boost energy levels and reduce fatigue:
The ability of NAD+ to induce weight loss can be attributed to its energy-boosting mechanisms. With increased energy expenditure, the body will not store additional fat. Instead, the metabolism is increased, resulting in weight loss.
There’s a great deal of evidence supporting the fat-burning effects of NAD+:
The anti-aging effects of NAD+ can also help attenuate the age-related decline in muscle mass and strength. Evidence suggests that NAD+ reverses detrimental age-associated changes in muscle by boosting ATP production, increasing mitochondrial function, and reducing inflammation. [49]
Studies show that NAD+ can help combat loss of muscle mass and strength associated with aging and musculoskeletal disease:
A decline in NAD+ levels is associated with a number of neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and other brain disorders that cause cognitive dysfunction. [11] Interestingly, NAD+ has neuroprotective effects and the ability to decrease the production of reactive oxygen species (ROS), which are linked to a wide array of medical maladies including neurodegenerative diseases.
NAD+ can also help prevent cell death by regulating the activity of polyadenosine diphosphate-ribose polymerase 1 (PARP1). [56] PARP1 activity is usually increased in the brain of patients with Alzheimer’s disease and other neurodegenerative disease and is associated with increased deposition of abnormal protein structures in the brain. [57] Basically, NAD+ regulates PARP1 activity so that it will not kill too many cells before they can be repaired.
In addition, NAD+ plays important roles in a wide array of biological processes in the brain such as transmission of nerve signals, learning, and memory. [58] NAD+ helps increase the levels of brain chemicals called neurotransmitters, such as dopamine, serotonin, and norepinephrine, which are involved in a number of cognitive functions including memory, motivation, attention, mood, and emotions.
A number of strong scientific evidence suggests that NAD+ can help improve cognitive health:
Mitochondrial respiration malfunction and increased glucose uptake are usually observed in cancer cells. Interestingly, increasing NAD+ levels has been shown to boost mitochondrial respiration and reduce glucose (blood sugar) uptake. [97] By counteracting these processes, NAD+ can help prevent the growth of cancer cells.
Increased NAD+ levels can also help boost the activity of SIRT1 and SIRT6, both of which inhibit the growth and spread of tumors via alteration of beta-catenin signaling and reduction of glucose uptake. [98-99]
Studies suggest that NAD+ exerts its anti-cancer effects through several mechanisms:
NAD+ levels are essential for normal heart function and are associated with improved cardiac recovery from injury. Interestingly, SIRT3, one of the signaling proteins of NAD+, can help improve heart health by preventing enlargement of the heart and scarring. [105-107]
There’s increasing evidence supporting the cardiovascular benefits of NAD+:
NAD+ activates SIRT1 which in turn increases the production of nitric oxide, a substance that helps widen blood vessels to allow an increase in blood flow. This process reduces the pressure within the blood vessels.
A number of studies support the antihypertensive effects of NAD+:
NAD+ can help improve blood sugar levels by reducing glucose (blood sugar) uptake. This in turn prevents sudden spikes in blood sugar which can be detrimental to health. In addition, NAD+ can also help increase the body’s response to insulin, a hormone that regulates blood sugar.
There’s a good deal of evidence supporting the beneficial effects of NAD+ on blood sugar levels:
The age-related shortening of telomeres adversely affects the function of the immune system. These adverse changes can significantly increase the risk for severe infection and even death. Studies suggest that patients with significantly shortened telomeres are at higher risk for different medical conditions such as rheumatoid arthritis and diabetes mellitus (type 1 and type 2). [135-137] Since NAD+ activates SIRT1, it can help achieve longer and more stable telomeres. This has a positive impact on the overall function of the immune system.
Another mechanism that can help improve the immune function is by suppressing or decreasing the inflammatory response. NAD+ has been shown to possess potent anti-inflammatory properties that can help treat or ward off a broad range of inflammatory conditions.
There is a growing body of evidence that NAD+ can help strengthen immune function:
By activating SIRT1, NAD+ can produce protective effects on the liver. SIRT1 is known to improve liver health by maintaining mitochondrial integrity, improving cholesterol transport, and improving fatty acid homeostasis. [147-149]
Several lines of evidence suggest that NAD+ can help prevent the development of liver diseases:
Reduced levels of NAD+ also reduce sirtuin activity. This process is largely responsible for the age-related decline in kidney function.
Latest studies indicate that NAD+ is beneficial for kidney health:
NAD+ side effects are very uncommon. There have been some side effects associated with the use of this drug wherein the patient had one of the issues listed below at some point while being on NAD+. However, these side effects weren’t confirmed to be associated with the treatment and could have been a coincidence and not related to the use of NAD+. Despite this, it was listed as a side effect associated with NAD+ even though these associated side effects are very uncommon.
Side effects associated with NAD+ may include the following:
NAD, or Nicotinamide Adenine Dinucleotide, is a vital coenzyme found in all living cells. It plays a critical role in metabolism by enabling the transfer of electrons during cellular respiration, which is essential for the production of ATP, the cell’s main energy currency. NAD exists in two forms: NAD+ (oxidized) and NADH (reduced), facilitating redox reactions that are fundamental to the metabolic processes sustaining life.
Beyond its role in energy production, NAD is crucial for several other cellular functions. It is involved in DNA repair, signaling pathways, and maintaining the health of mitochondria, the powerhouses of the cell. NAD+ acts as a substrate for enzymes called sirtuins and PARPs (poly ADP-ribose polymerases), which are important for gene expression regulation, stress responses, and longevity. This makes NAD not only vital for immediate cellular energy needs but also for long-term cellular health and function.
As we age, NAD levels naturally decline, which is associated with reduced cellular function and increased susceptibility to age-related diseases. Research into NAD supplementation and ways to boost NAD levels has gained significant interest for its potential to improve healthspan and combat age-related conditions. Interventions such as NAD precursors (like nicotinamide riboside and nicotinamide mononucleotide) and lifestyle changes like calorie restriction and exercise are being studied for their effects on maintaining or restoring NAD levels in the body.
Nicotinamide Adenine Dinucleotide Phosphate (NADP) is a crucial coenzyme found in all living cells. It plays a vital role in metabolic processes, particularly in the anabolic reactions, such as lipid and nucleic acid synthesis, where it functions as an electron carrier. NADP is involved in the pentose phosphate pathway, a metabolic pathway parallel to glycolysis, which generates NADPH and ribose-5-phosphate, the latter being essential for nucleotide synthesis.
NADPH, the reduced form of NADP, is fundamental in maintaining cellular redox balance. It acts as a reducing agent in various biochemical reactions, providing the necessary electrons for the reduction of oxidized molecules. This is particularly important in protecting cells against oxidative stress by replenishing the supply of reduced glutathione, a critical antioxidant. Additionally, NADPH is vital for the biosynthesis of fatty acids and cholesterol, making it indispensable for cell growth and repair.
In the immune system, NADPH plays a critical role in the function of phagocytes, the cells that engulf and destroy pathogens. NADPH oxidase, an enzyme complex found in the membranes of these cells, utilizes NADPH to produce reactive oxygen species (ROS) during the respiratory burst, a rapid release of ROS used to kill invading microorganisms. This highlights the importance of NADP/NADPH not only in metabolic and biosynthetic pathways but also in the defense mechanisms against infections.
Nicotinamide adenine dinucleotide (NAD) supplements have gained popularity for their potential to enhance cellular energy production and support overall health. However, like any supplement, NAD supplements can have side effects. Common mild side effects reported by users include nausea, headaches, fatigue, and digestive discomfort. These symptoms are usually transient and may diminish as the body adjusts to the supplement. It is important for users to start with a lower dose and gradually increase it to minimize the risk of these mild adverse effects.
In some cases, individuals may experience more serious side effects, although these are less common. These can include allergic reactions, such as rash, itching, or swelling, and in rare instances, respiratory issues. If any severe reactions occur, it is crucial to discontinue use immediately and seek medical attention. Additionally, NAD supplements may interact with certain medications, so it is advisable for individuals taking prescription drugs or those with underlying health conditions to consult a healthcare provider before starting NAD supplementation.
Long-term effects of NAD supplementation are still under research, and while the initial findings are promising, it is essential to approach with caution. Overuse or excessively high doses of NAD supplements could potentially lead to imbalances in cellular metabolism or other unforeseen health issues. Therefore, it is important to adhere to recommended dosages and guidelines provided by health professionals. As with any supplement, the benefits and risks should be carefully weighed, and users should be mindful of any changes in their health while taking NAD supplements.
NAD (nicotinamide adenine dinucleotide) plays a crucial role in cellular respiration, acting as a key electron carrier in metabolic pathways. In glycolysis, the first stage of cellular respiration, NAD+ accepts electrons from the breakdown of glucose, becoming reduced to NADH. This process is essential for the continuation of glycolysis and the production of ATP, as NADH then transports these high-energy electrons to the next stages of cellular respiration.
In the Krebs cycle, NAD+ again functions as an electron acceptor. During this cycle, which takes place in the mitochondria, NAD+ is reduced to NADH multiple times as various intermediates are oxidized. The NADH produced carries the electrons to the electron transport chain (ETC), the final stage of cellular respiration. The continuous regeneration of NAD+ is vital for the Krebs cycle to proceed and for the production of additional ATP molecules.
The electron transport chain, located in the inner mitochondrial membrane, is where NADH plays a pivotal role in generating a large amount of ATP. NADH donates the electrons it carries to the ETC, initiating a series of redox reactions that pump protons across the membrane, creating an electrochemical gradient. This gradient drives the synthesis of ATP through oxidative phosphorylation. By facilitating these electron transfers, NAD ensures the efficient production of ATP, the energy currency of the cell, highlighting its essential role in cellular respiration.
Nicotinamide adenine dinucleotide (NAD) is a crucial coenzyme found in all living cells, playing a key role in metabolic processes and cellular energy production. Foods that boost NAD levels, often referred to as “NAD foods,” can support overall health and longevity by enhancing these critical functions. Key nutrients that help increase NAD levels include niacin (vitamin B3), tryptophan, and riboside. Incorporating foods rich in these nutrients into your diet can help maintain optimal NAD levels and promote better cellular health.
Niacin, found in foods such as turkey, chicken, peanuts, and mushrooms, is one of the most direct sources for boosting NAD levels. This vitamin is a precursor to NAD, meaning it is converted into NAD within the body, helping to support energy metabolism and cellular repair processes. Additionally, foods high in tryptophan, an essential amino acid that is a precursor to niacin, can also help increase NAD levels. These foods include dairy products, eggs, fish, and seeds.
Furthermore, riboside, another precursor to NAD, is found in smaller amounts in foods like milk and yeast. Though dietary sources are beneficial, some people might consider supplements for a more concentrated dose of NAD precursors. By focusing on a diet rich in these NAD-boosting foods, you can support your body’s energy production, enhance cellular repair mechanisms, and potentially improve overall health and longevity.
NAD injections involve the administration of nicotinamide adenine dinucleotide (NAD+) directly into the bloodstream. NAD+ is a coenzyme found in all living cells, playing a crucial role in cellular metabolism by facilitating the transfer of energy from nutrients to the cells. These injections are designed to boost levels of NAD+ in the body, which can decline due to aging, stress, and various health conditions.
Potential Benefits of NAD Injections NAD injections are believed to offer a range of health benefits. They are thought to enhance energy levels, improve mental clarity, and support cognitive function, potentially aiding in the treatment of neurodegenerative diseases such as Alzheimer’s and Parkinson’s. Additionally, NAD+ is essential for DNA repair and cellular regeneration, which may contribute to anti-aging effects and overall improved vitality. Some proponents also claim that NAD injections can aid in addiction recovery by reducing cravings and withdrawal symptoms.
Considerations and Risks While NAD injections may offer promising benefits, it is important to approach them with caution. Potential side effects can include nausea, fatigue, and headaches. Moreover, the long-term effects and safety of NAD supplementation are not yet fully understood, and more research is needed to confirm its efficacy and optimal dosing. As with any medical treatment, it is essential to consult with a healthcare professional before starting NAD injections to ensure they are appropriate for individual health needs and conditions.
Increasing NAD (nicotinamide adenine dinucleotide) levels naturally can be achieved through various lifestyle and dietary interventions. One effective method is engaging in regular physical exercise. Aerobic exercises such as running, swimming, and cycling have been shown to boost NAD levels by enhancing the activity of enzymes involved in NAD biosynthesis. Additionally, resistance training can also contribute to maintaining optimal NAD levels by promoting muscle health and metabolic function.
Another natural approach to boosting NAD levels is through dietary choices. Consuming foods rich in NAD precursors like tryptophan, nicotinamide riboside, and nicotinic acid can support NAD production in the body. These precursors are found in foods such as dairy products, fish, chicken, turkey, and whole grains. Furthermore, incorporating a diet that includes antioxidant-rich fruits and vegetables can help reduce oxidative stress, which in turn preserves NAD levels and supports overall cellular health.
Intermittent fasting and caloric restriction are also effective strategies for naturally increasing NAD levels. These dietary practices promote metabolic flexibility and enhance the activity of sirtuins, a family of proteins that rely on NAD for their function. By reducing caloric intake intermittently, the body can optimize its energy usage and improve NAD biosynthesis. This, combined with a healthy diet and regular exercise, can create a holistic approach to maintaining and boosting NAD levels naturally.
Nicotinamide Adenine Dinucleotide (NAD) powder is a supplement that provides the body with a form of NAD+, a vital coenzyme found in all living cells. NAD+ plays a crucial role in cellular energy production, particularly in the mitochondria, where it helps convert nutrients into adenosine triphosphate (ATP), the energy currency of the cell. Supplementing with NAD powder can help support cellular energy levels, potentially boosting overall vitality and endurance, which is especially beneficial for athletes and those experiencing fatigue or energy deficits.
Beyond its role in energy metabolism, NAD+ is essential for several other critical cellular processes, including DNA repair, gene expression, and maintaining the health of the immune system. NAD+ is a substrate for enzymes like sirtuins and PARPs, which are involved in regulating cellular stress responses, inflammation, and aging. By increasing NAD+ levels through supplementation with NAD powder, it may be possible to enhance these processes, promoting better cellular health and longevity. Research suggests that higher NAD+ levels can help mitigate age-related decline and improve resilience to various stressors.
The potential benefits of NAD powder are also being explored in the context of neurodegenerative diseases, such as Alzheimer’s and Parkinson’s disease. NAD+ supports neuronal health and function by protecting against oxidative stress and maintaining mitochondrial health. Preliminary studies indicate that boosting NAD+ levels might slow the progression of these diseases and improve cognitive function. Consequently, NAD powder supplementation could offer a promising avenue for supporting brain health and combating neurodegenerative conditions, though more research is needed to fully understand its effects and optimal usage.
NAD (nicotinamide adenine dinucleotide) IV therapy is a treatment that involves the intravenous infusion of NAD+, a coenzyme essential for cellular energy production and metabolic function. This therapy aims to boost the levels of NAD+ in the body, which naturally decline with age and are linked to various health issues, including neurodegenerative diseases, chronic fatigue, and substance addiction. By increasing NAD+ levels, the therapy supports cellular repair, enhances cognitive function, and promotes overall well-being.
The NAD IV therapy protocol typically involves a series of sessions where NAD+ is administered directly into the bloodstream through an intravenous drip. The duration and frequency of these sessions can vary depending on individual needs and health goals but generally range from several hours per session over a few consecutive days to weekly maintenance infusions. The concentration of NAD+ and the rate of infusion are carefully monitored by healthcare professionals to ensure safety and effectiveness, with adjustments made based on patient response and tolerance.
Patients undergoing NAD IV therapy often report increased energy, improved mental clarity, enhanced mood, and better overall physical performance. Additionally, it is used as a supportive treatment in addiction recovery, helping to reduce withdrawal symptoms and cravings. However, it is essential to conduct NAD IV therapy under the supervision of a qualified healthcare provider to minimize potential side effects, such as mild discomfort at the infusion site, nausea, or headaches. As research into NAD+ continues, its protocols and applications are expected to evolve, potentially offering broader therapeutic benefits.
Nicotinamide Adenine Dinucleotide (NAD+) is a coenzyme found in all living cells, playing a crucial role in cellular metabolism and energy production. It is involved in redox reactions, carrying electrons from one reaction to another, which is vital for the production of ATP, the cell’s main energy currency. NAD+ also serves as a substrate for important cellular processes, including DNA repair and the regulation of gene expression through sirtuins, a family of proteins that influence aging and longevity.
Supplementing with NAD+ or its precursors, such as Nicotinamide Riboside (NR) and Nicotinamide Mononucleotide (NMN), has gained attention for its potential health benefits. Research suggests that increasing NAD+ levels can improve mitochondrial function, enhance cellular repair mechanisms, and possibly delay the aging process. Studies have shown promising results in animal models, where NAD+ supplementation has been associated with improved muscle function, cognitive performance, and resistance to metabolic diseases.
Despite these promising findings, human research on NAD+ supplements is still in its early stages. While some clinical trials indicate benefits like increased energy levels, improved endurance, and better cognitive function, more extensive studies are needed to confirm these effects and determine the long-term safety of NAD+ supplementation. As interest grows, NAD+ supplements are becoming more widely available, but it is essential for consumers to approach them with cautious optimism and consult healthcare professionals before starting any new supplement regimen.
Nicotinamide adenine dinucleotide (NAD+) is a crucial coenzyme found in all living cells, playing a key role in metabolic processes. It is essential for converting food into energy by facilitating the transfer of electrons in the mitochondria during cellular respiration. This process is vital for generating adenosine triphosphate (ATP), the primary energy carrier in cells. Without adequate levels of NAD+, cells would struggle to perform their energy-requiring functions effectively.
Beyond its role in energy production, NAD+ is also involved in DNA repair and cellular signaling. It acts as a substrate for sirtuins, a family of proteins that regulate various cellular processes, including aging, inflammation, and stress responses. By supporting these functions, NAD+ helps maintain cellular health and longevity, which has implications for aging and age-related diseases.
Recent research has highlighted the potential therapeutic uses of NAD+ in enhancing health and treating certain conditions. Supplementation with NAD+ precursors, such as nicotinamide riboside or nicotinamide mononucleotide, is being explored for its benefits in boosting cellular NAD+ levels. These benefits include improving metabolic health, enhancing cognitive function, and possibly extending lifespan. As a result, NAD+ has become a focus of interest in both aging research and clinical therapies.
Nicotinamide Adenine Dinucleotide (NAD) is a crucial coenzyme found in all living cells, essential for energy production and various metabolic processes. It exists in two forms: NAD+ and NADH. NAD+ plays a vital role in redox reactions, helping to convert nutrients into energy through cellular respiration. It also assists in DNA repair and regulates cellular aging and stress responses. As we age, NAD+ levels decline, which has been linked to several age-related diseases and metabolic disorders.
Nicotinamide Riboside (NR) is a precursor to NAD+, meaning it can be converted into NAD+ within the body. As a dietary supplement, NR has gained attention for its potential to boost NAD+ levels and thereby support cellular energy metabolism, enhance mitochondrial function, and mitigate the effects of aging. Research suggests that NR supplementation may improve metabolic health, cognitive function, and physical performance by increasing NAD+ levels and supporting various NAD+-dependent processes.
While both NAD+ and NR are essential for maintaining cellular health, their roles and applications differ. NAD+ is a fundamental molecule directly involved in metabolic processes, while NR serves as a supplement to increase NAD+ levels. NR supplementation may be beneficial in counteracting age-related declines in NAD+ and improving overall health, but it is important to understand that increasing NAD+ through NR does not directly replace the complex roles NAD+ plays in cellular functions.
Nicotinamide adenine dinucleotide (NAD) is crucial for energy production, DNA repair, and cellular metabolism. Nicotinic acid helps convert nutrients into energy, regulates cellular aging, and supports various biological processes essential for health. Nicotinic acid is also known for its role in promoting overall wellness.
Generally, nicotinic acid supplements are considered safe for most people, but potential side effects can include digestive issues, headaches, and dizziness. It is important to consult a healthcare provider before starting any new nicotinic acid supplement regimen
Research suggests that NAD+ supplements, which often include nicotinic acid, can effectively boost NAD+ levels, which may improve energy metabolism, support cellular repair, and mitigate age-related declines. Nicotinic acid is known to play a role in these processes, but the effectiveness can vary, and more research is needed to fully understand their benefits. The role of nicotinic acid in NAD+ supplementation continues to be an area of active investigation.
You can increase NAD+ levels naturally by consuming foods rich in nicotinic acid (vitamin B3) such as poultry, fish, and whole grains, engaging in regular exercise, maintaining a healthy diet, and managing stress. Nicotinic acid plays a crucial role in the production of NAD+, so incorporating it into your diet can be beneficial. Additionally, maintaining a healthy lifestyle and managing stress can further support the effects of nicotinic acid on NAD+ levels.
Yes, nicotinic acid, a form of vitamin B3, is a precursor to NAD+ and can help increase NAD+ levels in the body. Nicotinic acid plays a crucial role in the production of NAD+, and thus, its supplementation can help boost NAD+ levels. Incorporating nicotinic acid into your regimen may have beneficial effects on maintaining healthy NAD+ levels.
Nicotinamide is a precursor to NAD+, meaning it is converted into NAD+ in the body. Nicotinic acid is another form of vitamin B3 that is also involved in NAD+ synthesis. NAD+ is the active coenzyme involved in metabolic processes, whereas nicotinamide and nicotinic acid are both forms of vitamin B3 that support NAD+ synthesis.
No, NAD is not just vitamin B3; it is a coenzyme crucial for energy production and metabolic processes, involving various enzymes. However, NAD+ is derived from vitamin B3, which includes niacin and nicotinamide, and the enzymes involved play a key role in this process. The enzymes involved in these pathways help in the conversion and utilization of NAD+ for numerous biological functions.
NAD+ plays a key role in converting nutrients into energy by engaging enzymes involved in this process, supporting DNA repair through the activity of enzymes involved in maintaining genetic integrity, and regulating cellular metabolism with the help of enzymes involved in various metabolic pathways. It is essential for energy production in cells and overall metabolic functions.
NAD supplements are generally considered safe, but it is important to use them under medical supervision, especially if you have underlying health conditions or are taking other medications that might affect your metabolic health. Monitoring your metabolic health is crucial while using NAD supplements to ensure they are not interfering with any other treatments. Always consult with a healthcare provider to discuss how NAD supplements could impact your overall metabolic health.
Potential downsides of NAD supplements can include mild side effects such as digestive upset, headaches, and dizziness, potentially due to enzymes involved in the metabolism of these supplements. Long-term effects and interactions with other medications are not yet fully understood, including how they might affect enzymes involved in their breakdown. Further research is needed to clarify the role of enzymes involved in NAD supplement metabolism and their impact on health.
NAD (nicotinamide adenine dinucleotide) is a coenzyme that supports energy production, DNA repair, and various metabolic processes crucial for metabolic health. It is vital for cellular health and plays a role in regulating aging and stress responses, contributing significantly to overall metabolic health. By maintaining NAD levels, you can support metabolic health and optimize bodily functions.
Increasing NAD+ levels naturally can be achieved through a balanced diet rich in niacin, regular physical activity, intermittent fasting, and maintaining overall good health practices. These strategies support critical cellular processes and contribute to improved cellular function. By engaging in these activities, you can help enhance critical cellular processes that are vital for overall health. Additionally, focusing on these approaches can positively impact the critical cellular processes involved in energy production and repair.
The main function of NAD+ is to facilitate redox reactions in the body, helping to convert nutrients into energy, support cellular repair, and regulate metabolic processes. Recent human clinical trials have investigated how NAD+ supplementation can influence these processes. Additionally, ongoing human clinical trials are exploring the broader implications of NAD+ on overall health and longevity.
Yes, it is generally safe to take nicotinamide adenine dinucleotide (NAD+) supplements. However, it is recommended to consult with a healthcare provider to ensure they are appropriate for your health needs, as NAD+ plays a crucial role in various metabolic pathways. Understanding how NAD+ affects these metabolic pathways can help in evaluating its impact on your health. Additionally, your healthcare provider can provide guidance on how NAD+ supplements might influence these metabolic pathways and their relevance to your specific health goals.
NADH and NADPH are both forms of NAD. NADH is involved in energy production and redox reactions in cellular respiration, helping to regulate key metabolic processes. On the other hand, NADPH is primarily used in biosynthetic reactions and antioxidant defense to regulate key metabolic processes. Both NADH and NADPH play crucial roles in the body, contributing to the overall regulation of key metabolic processes.
NADH supports cellular energy production, enhances mental clarity, and may improve overall physical performance. As one of the dietary supplements, it is involved in redox reactions and can help combat oxidative stress. Incorporating NADH into your routine as part of your dietary supplements can be beneficial for overall health.
Individuals with certain medical conditions, those taking specific medications, or pregnant and breastfeeding women should consult a healthcare provider before using NAD supplements, as these supplements can affect multiple major biological processes. Consulting a healthcare provider is crucial to understand how NAD supplements might impact multiple major biological processes in your body. It’s important to ensure that the use of NAD supplements does not interfere with multiple major biological processes, especially in sensitive populations.
Yes, NAD supplements can be taken daily, but it’s important to follow dosage recommendations and consult a healthcare provider to determine the right amount for your needs, especially if you have metabolic disorders. People with metabolic disorders may benefit from NAD supplementation, but it’s crucial to consider the specific requirements related to these conditions. Always consult with a healthcare provider before starting any new supplement regimen, particularly if you’re dealing with metabolic disorders.
In cellular respiration, NAD+ acts as an electron carrier, transferring electrons from metabolic processes to the electron transport chain, which helps produce ATP, the primary energy currency of the cell. The process of cellular respiration is vital for human health, as it provides the energy necessary for various bodily functions. Understanding NAD+ and its role in cellular respiration can have significant implications for human health, particularly in the context of energy metabolism and disease prevention. Research into the ways NAD+ impacts cellular processes continues to be an important area of study in human health.
In glycolysis, NAD+ is reduced to NADH, which carries high-energy electrons to the electron transport chain for ATP production. This process is one of the essential cell processes crucial for energy metabolism. The role of NADH in the electron transport chain highlights another of the essential cell processes that sustain cellular function. Understanding these essential cell processes helps in comprehending how cells harness and utilize energy
NAD (nicotinamide adenine dinucleotide) and FAD (flavin adenine dinucleotide) are coenzymes that act as electron carriers in cellular respiration, facilitating the transfer of electrons in redox reactions and aiding ATP production. These coenzymes play a critical role in cellular energy metabolism, which may help ameliorate neurodegenerative diseases by supporting mitochondrial function. Studies suggest that optimizing NAD and FAD levels could potentially ameliorate neurodegenerative diseases by improving cellular resilience and energy production. Furthermore, their involvement in redox reactions and electron transport may also contribute to efforts to ameliorate neurodegenerative diseases by reducing oxidative stress and promoting cell survival.
Raising NAD+ levels naturally can be achieved through dietary sources rich in niacin, an essential amino acid, regular exercise, intermittent fasting, and maintaining a healthy lifestyle. Including foods that contain tryptophan, an essential amino acid, can also support NAD+ production. Overall, a balanced diet with sufficient intake of each essential amino acid, combined with a healthy lifestyle, contributes to optimal NAD+ levels.
Foods high in niacin (vitamin B3), such as turkey, chicken, fish, and whole grains, support NAD+ production, which is crucial for key cellular functions. NAD+ is not directly present in food but is derived from these nutrients, playing a vital role in key cellular functions. Maintaining adequate levels of NAD+ supports key cellular functions and overall health.
Factors such as aging, chronic stress, poor diet, excessive alcohol consumption, and certain medical conditions can deplete NAD+ levels in the body. Understanding these factors can be a potential therapeutic strategy to address NAD+ depletion. Additionally, developing a potential therapeutic strategy to combat these issues could improve overall health. Implementing lifestyle changes and medical interventions as a potential therapeutic strategy may help maintain optimal NAD+ levels.
An NAD injection is a medical procedure where NAD+ is administered directly into the bloodstream to boost NAD+ levels quickly, often used for therapeutic purposes such as enhancing energy and mental clarity. This treatment has gained attention for its potential benefits in managing age-associated diseases, as NAD+ plays a crucial role in cellular metabolism and overall health. By increasing NAD+ levels, NAD injections may help combat age-associated diseases and improve the quality of life for individuals experiencing symptoms related to these conditions. As research continues, the use of NAD injections in addressing age-associated diseases could become more prevalent.
NAD+ injections are reported to improve energy levels and cognitive function, potentially supporting metabolic homeostasis. However, more research is needed to fully understand their effectiveness and long-term benefits, particularly in the context of metabolic homeostasis. Maintaining metabolic homeostasis is crucial, and further studies are required to determine the role of NAD+ injections in achieving this balance.
The effects of NAD+ injections can vary, but typically, the benefits may last from a few days to a few weeks, depending on individual health and treatment frequency. Maintaining systemic health is crucial for maximizing the effectiveness of these injections. By focusing on maintaining systemic health, individuals may experience more sustained benefits. Additionally, maintaining systemic health can play a significant role in how long the effects of NAD+ injections last.
The cost of NAD+ injections can vary widely, typically ranging from $200 to $1,000 per session, depending on the provider and location. For individuals with metabolic disease, NAD+ injections might be considered as part of their treatment strategy. It’s important to consult with a healthcare provider to determine if these injections are appropriate for addressing their specific metabolic disease.
While foods do not contain NAD+ directly, foods rich in niacin (vitamin B3), such as chicken, fish, and whole grains, can help support NAD+ production in the body. The human PARP protein family plays a crucial role in this process, as these proteins are involved in NAD+ metabolism and repair mechanisms. By supporting NAD+ production, you indirectly support the functions of the human PARP protein family, which is essential for maintaining cellular health..
Increasing NAD+ levels can be achieved through dietary supplements like nicotinamide riboside (NR) or nicotinamide mononucleotide (NMN), regular exercise, and a healthy diet rich in niacin. These strategies can also positively influence glucose metabolism. By enhancing NAD+ levels, you support various cellular processes, including glucose metabolism. Regular physical activity, in particular, plays a crucial role in optimizing glucose metabolism and maintaining overall health
Vitamin B3, which includes niacin and nicotinamide, increases NAD+ levels as it is a precursor to NAD+. Fatty acid metabolism is closely linked to NAD+ production. Additionally, fatty acid levels can influence how effectively vitamin B3 boosts NAD+.
NAD powder is believed to support cellular energy production, enhance mental clarity, and potentially improve overall health by boosting NAD+ levels. By increasing NAD+ levels, NAD powder may help address metabolic dysfunction, which can impact cellular function. This improvement in cellular health might also mitigate issues related to metabolic dysfunction, potentially leading to better overall wellness.
Nicotinamide adenine dinucleotide (NAD) is used for energy production, DNA repair, and various metabolic processes. It supports cellular health and regulates aging and stress responses.
The frequency of NAD IV therapy varies depending on individual health goals and needs, as well as the alignment with one’s circadian rhythm. Typically, it may be administered weekly or monthly, considering the impact of circadian rhythm on overall well-being, as recommended by a healthcare provider. The scheduling of NAD IV therapy may also be adjusted to better align with the individual’s circadian rhythm.
The most effective way to take NAD can depend on individual needs and how it aligns with your circadian rhythm. Options include oral supplements, intravenous (IV) therapy, or sublingual forms, with the choice often guided by specific health goals and the impact on your circadian rhythm. It’s important to consider how NAD supplementation fits into your daily routine and circadian rhythm to achieve optimal results.
The appropriate dosage of NAD supplements can vary based on individual health needs. It is best to follow the dosage recommendations provided by the supplement manufacturer or a healthcare provider, as NAD acts as an essential cofactor in various biological processes. Ensuring the correct dosage is crucial because NAD, as an essential cofactor, supports critical functions in the body. Always consult with a healthcare provider to determine the right amount of NAD supplements for your needs, considering its role as an essential cofactor in maintaining overall health.
NAD can be administered orally through supplements, intravenously via IV therapy, or sublingually (under the tongue) to increase its bioavailability and effectiveness. This approach promotes neuronal morphogenesis, potentially enhancing cognitive functions. Additionally, by promoting neuronal morphogenesis, NAD supports overall brain health. Finally, the increased bioavailability of NAD through these methods can further facilitate processes that promote neuronal morphogenesis.
Yes, NAD+ supplements can generally be taken daily, as they are known to promote neuronal morphogenesis. However, it is important to follow dosage recommendations and consult with a healthcare provider to ensure appropriate use. Proper usage of NAD+ supplements promotes neuronal morphogenesis, which can support overall brain health. Always remember that NAD+ supplements promote neuronal morphogenesis, so it’s crucial to use them correctly and under professional guidance.
The best NAD supplement varies based on individual needs. Popular options include nicotinic acid adenine dinucleotide, nicotinamide riboside (NR), and nicotinamide mononucleotide (NMN). It’s best to choose a reputable brand and consult with a healthcare provider, especially if you’re considering nicotinic acid adenine dinucleotide as an option. Nicotinic acid adenine dinucleotide is known for its role in cellular energy production.
The main function of nicotinamide adenine dinucleotide (NAD) is to facilitate redox reactions in the body, aiding in energy production, DNA repair, and overall cellular metabolism. NAD plays a crucial role in the function of immune cells, supporting their activity and response. Additionally, NAD’s involvement in cellular metabolism impacts the health and efficiency of immune cells, contributing to the body’s overall well-being.
Nicotinamide NAD provides benefits such as improved energy production, enhanced cellular repair, better metabolic function, and support for cognitive and physical health, including in cases of traumatic brain injuries. This can be particularly valuable for those recovering from traumatic brain injuries, as Nicotinamide NAD aids in cellular repair processes. Additionally, its role in supporting cognitive and physical health may offer benefits for individuals who have experienced traumatic brain injuries.
No, nicotinamide riboside (NR) is a precursor to NAD+, meaning it is converted into NAD+ in the body. NR supplements are used to increase NAD+ levels, which can contribute to improved metabolic health. By boosting NAD+ levels, NR supplements may support various aspects of improved metabolic health. This includes enhancing cellular energy production and potentially promoting overall well-being through improved metabolic health.
The choice between NAD and NADH supplements depends on individual health goals. NADH is involved in energy production and can improve physical and mental performance, while NAD+ is crucial for overall metabolic processes and cellular health. Addressing genomic instability can be an important aspect of using these supplements, as both NAD and NADH play roles in maintaining cellular integrity. Considering genomic instability in the context of NAD+ and NADH supplementation may help optimize their benefits for overall well-being and potentially mitigate axonal degeneration. It is essential to understand how these supplements might influence axonal degeneration and other neurodegenerative processes. Therefore, the impact of NAD+ and NADH on axonal degeneration should be considered when evaluating their overall benefits for health.
The best form of nicotinamide often depends on individual needs and health goals. Common forms include nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), which are effective in boosting NAD+ levels. For those concerned about age related diseases like cardiovascular disease, both NR and NMN have shown potential benefits. Additionally, maintaining optimal NAD+ levels may play a role in reducing the risk of age related diseases such as cardiovascular disease
No, nicotinamide adenine dinucleotide (NAD) is not banned. It is a naturally occurring molecule and is available in various supplement forms. NAD is derived from vitamin precursors and plays a crucial role in cellular processes. Supplements containing NAD or its vitamin precursors can help support overall health and potentially mitigate age-related diseases. By supporting cellular function, NAD supplements may also contribute to reducing the impact of age-related diseases.
NAD supplements may cause unusual sensations or side effects, such as dizziness or nausea, in some individuals. However, despite these potential side effects, NAD supplements can offer beneficial effects for overall health. These effects, which can be understood better through cellular biology, can vary based on dosage and individual sensitivity. Consulting with a healthcare provider can help address any concerns and maximize the beneficial effects of NAD supplementation, which can be explained through the lens of cellular biology.
Monaghan, P., & Haussmann, M. F. (2006). Do telomere dynamics link lifestyle and lifespan?. Trends in ecology & evolution, 21(1), 47–53. https://doi.org/10.1016/j.tree.2005.11.007.
Do telomere dynamics link lifestyle and lifespan?
In their paper, Monaghan and Haussmann (2006) investigate the potential link between lifestyle factors and telomere dynamics, which are key determinants of cellular aging and lifespan. Telomeres, the protective caps at the ends of chromosomes, undergo shortening with each cell division, eventually leading to cellular senescence and aging. The authors explore how lifestyle choices, such as diet, exercise, and stress levels, may influence telomere length and maintenance mechanisms.
Their review highlights emerging evidence suggesting that certain lifestyle factors, such as regular exercise and a healthy diet, may promote telomere length maintenance and delay cellular aging. Conversely, factors like chronic stress and unhealthy behaviors may accelerate telomere shortening and contribute to premature aging.
Full article on https://www.cell.com/trends/ecology-evolution/fulltext/S0169-5347(05)00371-X?large_figure=true
Monaghan P. (2010). Telomeres and life histories: the long and the short of it. Annals of the New York Academy of Sciences, 1206, 130–142. https://doi.org/10.1111/j.1749-6632.2010.05705.x.
Telomeres and life histories: the long and the short of it
In his paper, Monaghan (2010) delves into the intricate relationship between telomeres and life histories, exploring how telomere dynamics influence various aspects of organismal biology, including aging, longevity, and life history traits. Telomeres, the protective caps at the ends of chromosomes, play a crucial role in maintaining genomic stability and regulating cellular lifespan.
Monaghan reviews empirical evidence from studies across diverse organisms, from humans to birds and mammals, to elucidate the connections between telomere length, environmental factors, and life history traits such as reproductive strategies and lifespan. He discusses how telomere dynamics can reflect the balance between investment in reproduction and somatic maintenance, influencing evolutionary trade-offs between these competing demands.
Full article on https://nyaspubs.onlinelibrary.wiley.com/doi/abs/10.1111/j.1749-6632.2010.05705.x
Palacios, J. A., Herranz, D., De Bonis, M. L., Velasco, S., Serrano, M., & Blasco, M. A. (2010). SIRT1 contributes to telomere maintenance and augments global homologous recombination. The Journal of cell biology, 191(7), 1299–1313. https://doi.org/10.1083/jcb.201005160.
SIRT1 contributes to telomere maintenance and augments global homologous recombination
In their study, Palacios et al. (2010) investigate the role of the protein SIRT1 in telomere maintenance and DNA repair processes. SIRT1 is a member of the sirtuin family of proteins known for their involvement in various cellular functions, including aging and DNA repair.
The researchers demonstrate that SIRT1 contributes to telomere maintenance by promoting the recruitment of telomere-binding proteins and preventing telomere dysfunction. Additionally, they find that SIRT1 enhances global homologous recombination, a DNA repair mechanism crucial for maintaining genomic stability.
These findings shed light on the molecular mechanisms underlying telomere maintenance and DNA repair, highlighting the importance of SIRT1 in these processes. The study provides valuable insights into how SIRT1-mediated pathways contribute to cellular homeostasis and genome integrity, with potential implications for aging-related diseases and cancer.
Full article on https://rupress.org/jcb/article-abstract/191/7/1299/36318
Wang, Y., Oxer, D., & Hekimi, S. (2015). Mitochondrial function and lifespan of mice with controlled ubiquinone biosynthesis. Nature communications, 6, 6393. https://doi.org/10.1038/ncomms7393.
Mitochondrial function and lifespan of mice with controlled ubiquinone biosynthesis
In their study, Wang, Oxer, and Hekimi (2015) investigate the relationship between mitochondrial function and lifespan in mice with controlled ubiquinone biosynthesis. Ubiquinone, also known as coenzyme Q10, plays a crucial role in mitochondrial respiration and energy production.
The researchers manipulated the biosynthesis of ubiquinone in mice to generate animals with varying levels of this essential cofactor. They found that mice with reduced ubiquinone levels exhibited compromised mitochondrial function, including impaired respiratory chain activity and decreased ATP production. These mice also showed signs of accelerated aging, including reduced lifespan and increased oxidative damage to cellular components.
These findings suggest a direct link between mitochondrial function, ubiquinone levels, and lifespan in mice. The study provides valuable insights into the role of mitochondrial function in aging and highlights the potential importance of ubiquinone supplementation in promoting healthy aging.
Full article on https://www.nature.com/articles/ncomms7393
Lanza, I. R., & Nair, K. S. (2010). Mitochondrial function as a determinant of life span. Pflugers Archiv: European journal of physiology, 459(2), 277–289. https://doi.org/10.1007/s00424-009-0724-5.
Mitochondrial function as a determinant of life span
In their paper, Lanza and Nair (2010) explore the role of mitochondrial function as a determinant of lifespan. Mitochondria are essential organelles involved in energy production, metabolism, and various cellular processes. The authors discuss accumulating evidence suggesting that mitochondrial dysfunction contributes to aging and age-related diseases.
The review covers studies examining the relationship between mitochondrial function and lifespan across different organisms, including humans, rodents, and invertebrates. It discusses how alterations in mitochondrial structure, function, and dynamics can impact cellular homeostasis and ultimately influence lifespan.
Furthermore, the authors explore potential mechanisms through which mitochondrial function may affect aging, such as oxidative stress, mitochondrial DNA damage, and impaired energy metabolism. They also discuss interventions, such as calorie restriction and exercise, that have been shown to improve mitochondrial function and extend lifespan in experimental models.
Full article on https://link.springer.com/article/10.1007/s00424-009-0724-5
Imai S, Guarente L. NAD+ and sirtuins in aging and disease. Trends Cell Biol. 2014;24(8):464-471. doi:10.1016/j.tcb.2014.04.002.
NAD+ and sirtuins in aging and disease
In their review, Imai and Guarente (2014) delve into the roles of nicotinamide adenine dinucleotide (NAD+) and sirtuins in aging and disease. NAD+ is a coenzyme involved in various cellular processes, including energy metabolism, DNA repair, and gene expression regulation. Sirtuins are a family of NAD+-dependent protein deacetylases that play critical roles in cellular homeostasis and stress response.
The authors discuss how NAD+ levels decline with age and how this reduction is associated with mitochondrial dysfunction, genomic instability, and age-related diseases. They also highlight the importance of sirtuins in mediating the beneficial effects of calorie restriction and exercise on lifespan and healthspan.
Furthermore, the review explores emerging evidence suggesting that boosting NAD+ levels or activating sirtuins may have therapeutic potential for treating age-related diseases, including metabolic disorders, neurodegenerative diseases, and cancer.
Full article on https://www.cell.com/trends/cell-biology/fulltext/S0962-8924(14)00063-4?elsca1=etoc&elsca2=email&elsca3=0962-8924_201408_24_8_&elsca4=Cell+Press
Tang B. L. (2016). Sirt1 and the Mitochondria. Molecules and cells, 39(2), 87–95. https://doi.org/10.14348/molcells.2016.2318.
Sirt1 and the Mitochondria
In his paper, Tang (2016) explores the intricate relationship between Sirtuin 1 (Sirt1) and mitochondria, two critical players in cellular homeostasis and longevity. Sirt1 is a member of the sirtuin family of proteins, known for their involvement in various cellular processes, including metabolism, stress response, and aging.
Tang discusses the multifaceted roles of Sirt1 in regulating mitochondrial function, dynamics, and biogenesis. Sirt1 has been shown to modulate mitochondrial activity by deacetylating key targets involved in mitochondrial metabolism and oxidative stress response. Additionally, Sirt1 plays a role in regulating mitochondrial dynamics, such as fission and fusion processes, which are essential for maintaining mitochondrial health and function.
Furthermore, the paper explores the impact of Sirt1 on mitochondrial biogenesis, the process by which new mitochondria are generated, highlighting its importance in cellular energy production and overall metabolic health.
Full article on https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4757807/
Belenky, P., Racette, F. G., Bogan, K. L., McClure, J. M., Smith, J. S., & Brenner, C. (2007). Nicotinamide riboside promotes Sir2 silencing and extends lifespan via Nrk and Urh1/Pnp1/Meu1 pathways to NAD+. Cell, 129(3), 473–484. https://doi.org/10.1016/j.cell.2007.03.024.
Nicotinamide riboside promotes Sir2 silencing and extends lifespan via Nrk and Urh1/Pnp1/Meu1 pathways to NAD+
In their study, Belenky et al. (2007) investigate the mechanisms through which nicotinamide riboside (NR) promotes lifespan extension via NAD+ metabolism and the sirtuin pathway. NAD+ is a crucial coenzyme involved in various cellular processes, including energy metabolism, DNA repair, and gene expression regulation. Sirtuins, such as Sir2, are a family of NAD+-dependent protein deacetylases implicated in aging and longevity.
The researchers demonstrate that NR supplementation increases NAD+ levels in yeast and mammalian cells, leading to enhanced Sir2 activity and lifespan extension. They identify the Nrk and Urh1/Pnp1/Meu1 pathways as mediators of NR conversion to NAD+.
Furthermore, the study highlights the importance of NAD+ metabolism in regulating sirtuin activity and cellular aging. By modulating NAD+ levels, NR promotes Sir2-mediated gene silencing and enhances lifespan in yeast and Caenorhabditis elegans models.
Full article on https://www.cell.com/fulltext/S0092-8674(07)00390-X
Fang, E. F., Kassahun, H., Croteau, D. L., Scheibye-Knudsen, M., Marosi, K., Lu, H., Shamanna, R. A., Kalyanasundaram, S., Bollineni, R. C., Wilson, M. A., Iser, W. B., Wollman, B. N., Morevati, M., Li, J., Kerr, J. S., Lu, Q., Waltz, T. B., Tian, J., Sinclair, D. A., Mattson, M. P., … Bohr, V. A. (2016). NAD+ Replenishment Improves Lifespan and Healthspan in Ataxia Telangiectasia Models via Mitophagy and DNA Repair. Cell metabolism, 24(4), 566–581. https://doi.org/10.1016/j.cmet.2016.09.004.
NAD+ replenishment improves lifespan and healthspan in ataxia telangiectasia models via mitophagy and DNA repair
In their study, Fang et al. (2016) investigate the effects of nicotinamide adenine dinucleotide (NAD+) replenishment on lifespan and healthspan in models of Ataxia Telangiectasia (A-T), a genetic disorder characterized by neurological degeneration and premature aging. NAD+ is a crucial coenzyme involved in various cellular processes, including energy metabolism, DNA repair, and mitochondrial function.
The researchers demonstrate that NAD+ replenishment extends lifespan and improves healthspan in A-T mouse models by promoting mitophagy, the selective degradation of damaged mitochondria, and enhancing DNA repair mechanisms. By boosting NAD+ levels, they observe a reduction in DNA damage accumulation and oxidative stress, leading to improved neuronal function and overall health in A-T mice.
Furthermore, the study elucidates the underlying molecular mechanisms through which NAD+ supplementation exerts its beneficial effects, including activation of the SIRT1 pathway, promotion of mitochondrial biogenesis, and enhancement of DNA repair capacity.
Full article on https://www.cell.com/cell-metabolism/pdf/S1550-4131(16)30482-X.pdf
Harlan, B. A., Killoy, K. M., Pehar, M., Liu, L., Auwerx, J., & Vargas, M. R. (2020). Evaluation of the NAD+ biosynthetic pathway in ALS patients and effect of modulating NAD+ levels in hSOD1-linked ALS mouse models. Experimental neurology, 327, 113219. https://doi.org/10.1016/j.expneurol.2020.113219.
Evaluation of the NAD+ biosynthetic pathway in ALS patients and effect of modulating NAD+ levels in hSOD1-linked ALS mouse models
In their study, Harlan et al. (2020) assess the NAD+ biosynthetic pathway in patients with amyotrophic lateral sclerosis (ALS) and investigate the effects of modulating NAD+ levels in mouse models of ALS linked to human superoxide dismutase 1 (hSOD1). ALS is a progressive neurodegenerative disease characterized by the loss of motor neurons, leading to muscle weakness and paralysis.
The researchers evaluate the NAD+ biosynthetic pathway in ALS patients and find alterations in NAD+ metabolism compared to healthy controls, suggesting dysregulation of NAD+ homeostasis in ALS pathophysiology. They then explore the effects of modulating NAD+ levels through supplementation or genetic manipulation in hSOD1-linked ALS mouse models.
Full article on https://www.sciencedirect.com/science/article/pii/S0014488620300509
Zhang, H., Ryu, D., Wu, Y., Gariani, K., Wang, X., Luan, P., D’Amico, D., Ropelle, E. R., Lutolf, M. P., Aebersold, R., Schoonjans, K., Menzies, K. J., & Auwerx, J. (2016). NAD⁺ repletion improves mitochondrial and stem cell function and enhances life span in mice. Science (New York, N.Y.), 352(6292), 1436–1443. https://doi.org/10.1126/science.aaf2693.
NAD+ repletion improves mitochondrial and stem cell function and enhances life span in mice
In their study, Zhang et al. (2016) investigate the effects of nicotinamide adenine dinucleotide (NAD+) repletion on mitochondrial function, stem cell function, and lifespan in mice. NAD+ is a vital coenzyme involved in various cellular processes, including energy metabolism, DNA repair, and gene expression regulation.
The researchers demonstrate that NAD+ repletion through supplementation with its precursor, nicotinamide riboside (NR), enhances mitochondrial function by promoting oxidative metabolism and mitochondrial biogenesis. Additionally, NAD+ supplementation improves stem cell function and enhances tissue regeneration capacity in aged mice.
Furthermore, the study reveals that NAD+ repletion extends lifespan in mice, highlighting the potential of targeting NAD+ metabolism as a strategy for promoting healthy aging. The beneficial effects of NAD+ supplementation are attributed to its role in enhancing cellular resilience to stress, promoting tissue repair, and delaying the onset of age-related pathologies.
Full article on https://www.science.org/doi/abs/10.1126/science.aaf2693
Peclat, T. R., Thompson, K. L., Warner, G. M., Chini, C., Tarragó, M. G., Mazdeh, D. Z., Zhang, C., Zavala-Solorio, J., Kolumam, G., Liang Wong, Y., Cohen, R. L., & Chini, E. N. (2022). CD38 inhibitor 78c increases mice lifespan and healthspan in a model of chronological aging. Aging cell, 21(4), e13589. https://doi.org/10.1111/acel.13589.
CD38 inhibitor 78c increases mice lifespan and healthspan in a model of chronological aging
In their study, Peclat et al. (2022) investigate the effects of a CD38 inhibitor, 78c, on lifespan and healthspan in a model of chronological aging in mice. CD38 is an enzyme involved in various cellular processes, including calcium signaling, immune response, and metabolism. It also plays a role in NAD+ metabolism, as it consumes NAD+ during its enzymatic activity.
The researchers demonstrate that inhibition of CD38 with 78c extends both lifespan and healthspan in mice undergoing chronological aging. They observe improvements in various health parameters, including metabolic health, immune function, and cognitive function, in mice treated with 78c compared to untreated controls.
Furthermore, the study elucidates the underlying mechanisms through which CD38 inhibition exerts its beneficial effects. The researchers find that 78c treatment leads to increased NAD+ levels and activation of the NAD+-dependent enzyme SIRT1, which is known to promote cellular resilience to stress and enhance longevity.
Full article on https://onlinelibrary.wiley.com/doi/abs/10.1111/acel.13589
Hashimoto, T., Horikawa, M., Nomura, T., & Sakamoto, K. (2010). Nicotinamide adenine dinucleotide extends the lifespan of Caenorhabditis elegans mediated by sir-2.1 and daf-16. Biogerontology, 11(1), 31–43. https://doi.org/10.1007/s10522-009-9225-3.
Nicotinamide adenine dinucleotide extends the lifespan of Caenorhabditis elegans mediated by sir-2.1 and daf-16
In their study, Hashimoto et al. (2010) investigate the effect of nicotinamide adenine dinucleotide (NAD+) on the lifespan of Caenorhabditis elegans, a commonly used model organism for aging research. NAD+ is a coenzyme involved in various cellular processes, including energy metabolism and regulation of gene expression.
The researchers demonstrate that supplementation with NAD+ extends the lifespan of C. elegans. They further elucidate the underlying molecular mechanisms by which NAD+ exerts its lifespan-extending effects, focusing on the involvement of two key regulatory genes: sir-2.1 and daf-16.
Sir-2.1 is a homolog of the mammalian sirtuin SIRT1, while daf-16 is a FOXO transcription factor involved in the insulin/IGF-1 signaling pathway. Hashimoto et al. show that NAD+ supplementation increases the expression and activity of sir-2.1 and daf-16, leading to enhanced stress resistance and longevity in C. elegans.
Full article on https://link.springer.com/article/10.1007/s10522-009-9225-3
Mouchiroud, L., Houtkooper, R. H., Moullan, N., Katsyuba, E., Ryu, D., Cantó, C., Mottis, A., Jo, Y. S., Viswanathan, M., Schoonjans, K., Guarente, L., & Auwerx, J. (2013). The NAD(+)/Sirtuin Pathway Modulates Longevity through Activation of Mitochondrial UPR and FOXO Signaling. Cell, 154(2), 430–441. https://doi.org/10.1016/j.cell.2013.06.016.
The NAD+/sirtuin pathway modulates longevity through activation of mitochondrial UPR and FOXO signaling
In their study, Mouchiroud et al. (2013) investigate the role of the nicotinamide adenine dinucleotide (NAD+)/sirtuin pathway in modulating longevity and aging-related processes. NAD+ is a crucial coenzyme involved in various cellular processes, including energy metabolism, DNA repair, and gene expression regulation. Sirtuins are a family of NAD+-dependent protein deacetylases that have been implicated in aging and longevity.
The researchers demonstrate that activation of the NAD+/sirtuin pathway extends lifespan in model organisms, including Caenorhabditis elegans and Drosophila melanogaster. They elucidate the underlying mechanisms through which NAD+/sirtuin signaling exerts its beneficial effects on longevity.
Full article on https://www.cell.com/fulltext/S0092-8674(13)00755-1
Odoh, C. K., Guo, X., Arnone, J. T., Wang, X., & Zhao, Z. K. (2022). The role of NAD and NAD precursors on longevity and lifespan modulation in the budding yeast, Saccharomyces cerevisiae. Biogerontology, 23(2), 169–199. https://doi.org/10.1007/s10522-022-09958-x.
The role of NAD and NAD precursors on longevity and lifespan modulation in the budding yeast, Saccharomyces cerevisiae
In their study, Odoh et al. (2022) investigate the role of nicotinamide adenine dinucleotide (NAD+) and NAD+ precursors in modulating longevity and lifespan in the budding yeast, Saccharomyces cerevisiae. NAD+ is a crucial coenzyme involved in various cellular processes, including energy metabolism, DNA repair, and gene expression regulation.
The researchers explore the effects of NAD+ and NAD+ precursors, such as nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), on yeast lifespan using genetic and pharmacological interventions. They demonstrate that supplementation with NAD+ precursors extends the replicative and chronological lifespan of yeast cells.
Full article on https://link.springer.com/article/10.1007/s10522-022-09958-x
Sun, N., Youle, R. J., & Finkel, T. (2016). The Mitochondrial Basis of Aging. Molecular cell, 61(5), 654–666. https://doi.org/10.1016/j.molcel.2016.01.028.
The Mitochondrial Basis of Aging
In their comprehensive review, Sun, Youle, and Finkel (2016) explore the intricate relationship between mitochondria and the aging process. Mitochondria are vital organelles responsible for generating cellular energy and regulating various cellular processes. The review delves into how mitochondrial dysfunction contributes to the aging process at the cellular and organismal levels.
The authors discuss several key mechanisms through which mitochondria influence aging, including oxidative stress, mitochondrial DNA (mtDNA) mutations, impaired mitochondrial dynamics, and alterations in mitochondrial metabolism. They highlight the concept of the mitochondrial free radical theory of aging, which proposes that the accumulation of oxidative damage to mtDNA and proteins over time leads to mitochondrial dysfunction and contributes to aging-related decline.
Full article on https://www.cell.com/molecular-cell/pdf/S1097-2765(16)00081-2.pdf
Gomes, A. P., Price, N. L., Ling, A. J., Moslehi, J. J., Montgomery, M. K., Rajman, L., White, J. P., Teodoro, J. S., Wrann, C. D., Hubbard, B. P., Mercken, E. M., Palmeira, C. M., de Cabo, R., Rolo, A. P., Turner, N., Bell, E. L., & Sinclair, D. A. (2013). Declining NAD(+) induces a pseudohypoxic state disrupting nuclear-mitochondrial communication during aging. Cell, 155(7), 1624–1638. https://doi.org/10.1016/j.cell.2013.11.037.
Declining NAD+ induces a pseudohypoxic state disrupting nuclear-mitochondrial communication during aging
In their groundbreaking study, Gomes et al. (2013) investigate the role of declining levels of nicotinamide adenine dinucleotide (NAD+) in disrupting nuclear-mitochondrial communication during aging. NAD+ is a crucial coenzyme involved in various cellular processes, including energy metabolism, DNA repair, and gene expression regulation.
The researchers demonstrate that NAD+ levels decline with age in multiple tissues and organisms, including mice and humans. This decline in NAD+ levels leads to impaired mitochondrial function, altered gene expression patterns, and a state of pseudohypoxia, characterized by activation of hypoxia-inducible factor 1-alpha (HIF-1α) signaling.
Full article on https://www.cell.com/abstract/S0092-8674%2813%2901521-3?wptouch_preview_theme=enabled
Das, A., Huang, G. X., Bonkowski, M. S., Longchamp, A., Li, C., Schultz, M. B., Kim, L. J., Osborne, B., Joshi, S., Lu, Y., Treviño-Villarreal, J. H., Kang, M. J., Hung, T. T., Lee, B., Williams, E. O., Igarashi, M., Mitchell, J. R., Wu, L. E., Turner, N., Arany, Z., … Sinclair, D. A. (2018). Impairment of an Endothelial NAD+-H2S Signaling Network Is a Reversible Cause of Vascular Aging. Cell, 173(1), 74–89.e20. https://doi.org/10.1016/j.cell.2018.02.008.
Impairment of an endothelial NAD+-H2S signaling network is a reversible cause of vascular aging
In their groundbreaking study, Das et al. (2018) investigate the role of an endothelial NAD+-H2S signaling network in vascular aging and explore its potential as a reversible mechanism underlying age-related vascular dysfunction. Endothelial cells play a crucial role in maintaining vascular homeostasis, and dysfunction of these cells is a hallmark of vascular aging and age-related diseases.
The researchers demonstrate that impairment of the NAD+-H2S signaling network contributes to vascular aging by promoting endothelial cell senescence and dysfunction. They show that age-related decline in NAD+ levels leads to decreased activity of the enzyme cystathionine gamma-lyase (CSE), which is responsible for generating hydrogen sulfide (H2S) in endothelial cells.
Full article on https://www.cell.com/cell/pdf/S0092-8674(18)30152-1.pdf
Ryu, D., Zhang, H., Ropelle, E. R., Sorrentino, V., Mázala, D. A., Mouchiroud, L., Marshall, P. L., Campbell, M. D., Ali, A. S., Knowels, G. M., Bellemin, S., Iyer, S. R., Wang, X., Gariani, K., Sauve, A. A., Cantó, C., Conley, K. E., Walter, L., Lovering, R. M., Chin, E. R., … Auwerx, J. (2016). NAD+ repletion improves muscle function in muscular dystrophy and counters global PARylation. Science translational medicine, 8(361), 361ra139. https://doi.org/10.1126/scitranslmed.aaf5504.
NAD+ repletion improves muscle function in muscular dystrophy and counters global PARylation
In their study, Ryu et al. (2016) investigate the therapeutic potential of nicotinamide adenine dinucleotide (NAD+) repletion in improving muscle function in muscular dystrophy and countering global poly(ADP-ribosyl)ation (PARylation). Muscular dystrophy is a group of genetic disorders characterized by progressive muscle weakness and degeneration.
The researchers demonstrate that NAD+ repletion improves muscle function in a mouse model of muscular dystrophy. They show that increased NAD+ levels lead to enhanced mitochondrial function, improved muscle strength, and reduced muscle damage and inflammation in dystrophic mice.
Furthermore, Ryu et al. elucidate the underlying mechanisms through which NAD+ repletion exerts its beneficial effects on muscle function. They demonstrate that increased NAD+ levels counteract global PARylation, a process associated with DNA damage and impaired muscle function in muscular dystrophy.
Full article on https://www.science.org/doi/abs/10.1126/scitranslmed.aaf5504
Mills, K. F., Yoshida, S., Stein, L. R., Grozio, A., Kubota, S., Sasaki, Y., Redpath, P., Migaud, M. E., Apte, R. S., Uchida, K., Yoshino, J., & Imai, S. I. (2016). Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age-Associated Physiological Decline in Mice. Cell metabolism, 24(6), 795–806. https://doi.org/10.1016/j.cmet.2016.09.013.
Long-term administration of nicotinamide mononucleotide mitigates age-associated physiological decline in mice
In their study, Mills et al. (2016) investigate the effects of long-term administration of nicotinamide mononucleotide (NMN) on age-associated physiological decline in mice. NMN is a precursor of nicotinamide adenine dinucleotide (NAD+), a crucial coenzyme involved in various cellular processes, including energy metabolism, DNA repair, and gene expression regulation.
The researchers demonstrate that long-term supplementation with NMN mitigates age-related physiological decline in multiple tissues and organs in mice. They show that NMN treatment improves mitochondrial function, enhances oxidative metabolism, and promotes energy expenditure in aged mice.
Full article on https://www.cell.com/cell-metabolism/pdf/S1550-4131(16)30495-8.pdf
Lin, J. B., Kubota, S., Ban, N., Yoshida, M., Santeford, A., Sene, A., Nakamura, R., Zapata, N., Kubota, M., Tsubota, K., Yoshino, J., Imai, S. I., & Apte, R. S. (2016). NAMPT-Mediated NAD(+) Biosynthesis Is Essential for Vision In Mice. Cell reports, 17(1), 69–85. https://doi.org/10.1016/j.celrep.2016.08.073.
NAMPT-Mediated NAD(+) Biosynthesis Is Essential for Vision In Mice
In their study, Lin et al. (2016) investigate the importance of nicotinamide phosphoribosyltransferase (NAMPT)-mediated nicotinamide adenine dinucleotide (NAD+) biosynthesis for vision in mice. NAD+ is a crucial coenzyme involved in various cellular processes, including energy metabolism, DNA repair, and gene expression regulation.
The researchers demonstrate that NAMPT-mediated NAD+ biosynthesis is essential for maintaining vision in mice. They show that genetic deletion of Nampt in the retina leads to decreased NAD+ levels, impaired mitochondrial function, and degeneration of photoreceptor cells, resulting in vision loss.
Full article on https://www.cell.com/cell-reports/pdf/S2211-1247(16)31169-X.pdf
Khan, N. A., Auranen, M., Paetau, I., Pirinen, E., Euro, L., Forsström, S., Pasila, L., Velagapudi, V., Carroll, C. J., Auwerx, J., & Suomalainen, A. (2014). Effective treatment of mitochondrial myopathy by nicotinamide riboside, a vitamin B3. EMBO molecular medicine, 6(6), 721–731. https://doi.org/10.1002/emmm.201403943.
Effective treatment of mitochondrial myopathy by nicotinamide riboside, a vitamin B3
In their study, Khan et al. (2014) investigate the efficacy of nicotinamide riboside (NR), a form of vitamin B3, in treating mitochondrial myopathy, a genetic disorder characterized by muscle weakness and fatigue due to dysfunctional mitochondria. Mitochondria are responsible for generating cellular energy, and defects in mitochondrial function can lead to various disorders, including mitochondrial myopathy.
The researchers demonstrate that NR supplementation effectively alleviates symptoms of mitochondrial myopathy in a mouse model of the disease. They show that NR treatment increases nicotinamide adenine dinucleotide (NAD+) levels and enhances mitochondrial function in muscle tissues, leading to improved muscle strength and endurance in affected mice.
Full article on https://www.embopress.org/doi/abs/10.1002/emmm.201403943
Brown, K. D., Maqsood, S., Huang, J. Y., Pan, Y., Harkcom, W., Li, W., Sauve, A., Verdin, E., & Jaffrey, S. R. (2014). Activation of SIRT3 by the NAD⁺ precursor nicotinamide riboside protects from noise-induced hearing loss. Cell metabolism, 20(6), 1059–1068. https://doi.org/10.1016/j.cmet.2014.11.003.
Activation of SIRT3 by the NAD+ precursor nicotinamide riboside protects from noise-induced hearing loss
In their study, Brown et al. (2014) investigate the protective effects of nicotinamide riboside (NR), a precursor of nicotinamide adenine dinucleotide (NAD+), on noise-induced hearing loss by activating sirtuin 3 (SIRT3). SIRT3 is a mitochondrial deacetylase known to play a crucial role in protecting against oxidative stress and maintaining mitochondrial function.
The researchers demonstrate that NR supplementation activates SIRT3 in the cochlea, the auditory portion of the inner ear, and protects against noise-induced hearing loss in mice. They show that NR treatment increases NAD+ levels and enhances SIRT3 activity, leading to reduced oxidative stress and mitochondrial dysfunction in the cochlea in response to noise exposure.
Furthermore, Brown et al. elucidate the underlying mechanisms through which NR-mediated activation of SIRT3 protects against hearing loss. They demonstrate that SIRT3 activation promotes the expression of antioxidant enzymes and reduces the accumulation of reactive oxygen species (ROS) in the cochlea, thereby preserving auditory function and preventing noise-induced damage to hair cells and auditory neurons.
Full article on https://www.cell.com/fulltext/S1550-4131(14)00500-2
Yoshino, J., Mills, K. F., Yoon, M. J., & Imai, S. (2011). Nicotinamide mononucleotide, a key NAD(+) intermediate, treats the pathophysiology of diet- and age-induced diabetes in mice. Cell metabolism, 14(4), 528–536. https://doi.org/10.1016/j.cmet.2011.08.014.
Nicotinamide mononucleotide, a key NAD(+) intermediate, treats the pathophysiology of diet- and age-induced diabetes in mice
In their study, Yoshino et al. (2011) investigate the therapeutic potential of nicotinamide mononucleotide (NMN), a key intermediate in nicotinamide adenine dinucleotide (NAD+) biosynthesis, in treating the pathophysiology of diet- and age-induced diabetes in mice. NAD+ plays a crucial role in cellular energy metabolism, and its levels decline with aging and in conditions such as diabetes.
The researchers demonstrate that NMN supplementation effectively ameliorates glucose intolerance, insulin resistance, and pancreatic β-cell dysfunction in mice fed a high-fat diet or in aged mice. They show that NMN treatment increases NAD+ levels in various tissues, including skeletal muscle, liver, and pancreas, leading to improved glucose metabolism and insulin sensitivity.
Full article on https://www.cell.com/cell-metabolism/pdf/S1550-4131(11)00346-9.pdf
Yang, Q., Cong, L., Wang, Y., Luo, X., Li, H., Wang, H., Zhu, J., Dai, S., Jin, H., Yao, G., Shi, S., Hsueh, A. J., & Sun, Y. (2020). Increasing ovarian NAD+ levels improve mitochondrial functions and reverse ovarian aging. Free radical biology & medicine, 156, 1–10. https://doi.org/10.1016/j.freeradbiomed.2020.05.003.
In their study, Yang et al. (2020) investigate the role of nicotinamide adenine dinucleotide (NAD+) in ovarian aging and explore the potential therapeutic effects of increasing ovarian NAD+ levels on mitochondrial function and ovarian aging. Ovarian aging is characterized by a decline in ovarian function, including reduced follicle quality and decreased fertility, which are closely associated with mitochondrial dysfunction.
The researchers demonstrate that increasing NAD+ levels in the ovaries improves mitochondrial function and reverses ovarian aging in mice. They show that supplementation with nicotinamide riboside (NR), a precursor of NAD+, increases NAD+ levels in ovarian tissues and enhances mitochondrial biogenesis and oxidative phosphorylation, leading to improved follicle quality and ovarian function.
Full article on https://www.sciencedirect.com/science/article/pii/S0891584920304214
Roh, E., Myoung Kang, G., Young Gil, S., Hee Lee, C., Kim, S., Hong, D., Hoon Son, G., & Kim, M. S. (2018). Effects of Chronic NAD Supplementation on Energy Metabolism and Diurnal Rhythm in Obese Mice. Obesity (Silver Spring, Md.), 26(9), 1448–1456. https://doi.org/10.1002/oby.22263.
Effects of Chronic NAD Supplementation on Energy Metabolism and Diurnal Rhythm in Obese Mice
In their study, Roh et al. (2018) investigate the effects of chronic nicotinamide adenine dinucleotide (NAD+) supplementation on energy metabolism and diurnal rhythm in obese mice. Obesity is associated with dysregulation of energy metabolism and disruptions in circadian rhythms, which can contribute to metabolic dysfunction and weight gain.
The researchers demonstrate that chronic NAD+ supplementation improves energy metabolism and restores diurnal rhythm in obese mice. They show that supplementation with nicotinamide riboside (NR), a precursor of NAD+, increases NAD+ levels in various tissues, including adipose tissue, liver, and skeletal muscle, leading to enhanced mitochondrial function and oxidative metabolism.
Furthermore, Roh et al. elucidate the underlying mechanisms through which NAD+ supplementation exerts its beneficial effects on energy metabolism and diurnal rhythm. They demonstrate that NR treatment improves insulin sensitivity, reduces adiposity, and increases energy expenditure in obese mice, resulting in improved metabolic health and weight loss.
Full article on https://onlinelibrary.wiley.com/doi/abs/10.1002/oby.22263
Alegre, J., Rosés, J. M., Javierre, C., Ruiz-Baqués, A., Segundo, M. J., & de Sevilla, T. F. (2010). Nicotinamida adenina dinucleótido (NADH) en pacientes con síndrome de fatiga crónica [Nicotinamide adenine dinucleotide (NADH) in patients with chronic fatigue syndrome]. Revista clinica espanola, 210(6), 284–288. https://doi.org/10.1016/j.rce.2009.09.015.
Nicotinamide adenine dinucleotide (NADH) in patients with chronic fatigue syndrome
In their study, Alegre et al. (2010) investigate the potential therapeutic effects of nicotinamide adenine dinucleotide (NADH) supplementation in patients with chronic fatigue syndrome (CFS). Chronic fatigue syndrome is a complex disorder characterized by severe fatigue that is not alleviated by rest and is accompanied by various other symptoms, including cognitive impairment, sleep disturbances, and muscle pain.
The researchers conducted a clinical trial to evaluate the efficacy of NADH supplementation in alleviating symptoms and improving quality of life in patients with CFS. They administered NADH orally to patients with CFS and assessed various outcome measures, including fatigue severity, cognitive function, and overall well-being.
Full article on https://europepmc.org/article/med/20447621
Dehhaghi, M., Panahi, H., Kavyani, B., Heng, B., Tan, V., Braidy, N., & Guillemin, G. J. (2022). The Role of Kynurenine Pathway and NAD+ Metabolism in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Aging and disease, 13(3), 698–711. https://doi.org/10.14336/AD.2021.0824.
The Role of Kynurenine Pathway and NAD+ Metabolism in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
In their study, Dehhaghi et al. (2022) explore the role of the kynurenine pathway and nicotinamide adenine dinucleotide (NAD+) metabolism in the pathogenesis of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). ME/CFS is a debilitating condition characterized by persistent fatigue, cognitive impairment, and other symptoms that significantly impair daily functioning.
The researchers conducted a comprehensive review of the literature to examine the involvement of the kynurenine pathway and NAD+ metabolism in the pathophysiology of ME/CFS. They discuss the dysregulation of the kynurenine pathway, which leads to increased production of neurotoxic metabolites such as quinolinic acid and kynurenine, and its potential contribution to neuroinflammation, oxidative stress, and mitochondrial dysfunction observed in ME/CFS patients.
Full article on https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9116917/
Castro-Marrero, J., Segundo, M. J., Lacasa, M., Martinez-Martinez, A., Sentañes, R. S., & Alegre-Martin, J. (2021). Effect of Dietary Coenzyme Q10 Plus NADH Supplementation on Fatigue Perception and Health-Related Quality of Life in Individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Prospective, Randomized, Double-Blind, Placebo-Controlled Trial. Nutrients, 13(8), 2658. https://doi.org/10.3390/nu13082658.
Effect of Dietary Coenzyme Q10 Plus NADH Supplementation on Fatigue Perception and Health-Related Quality of Life in Individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Prospective, Randomized, Double-Blind, Placebo-Controlled Trial
In their study, Castro-Marrero et al. (2021) investigate the effect of dietary supplementation with coenzyme Q10 (CoQ10) plus nicotinamide adenine dinucleotide (NADH) on fatigue perception and health-related quality of life in individuals with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). ME/CFS is a complex and debilitating condition characterized by persistent fatigue, cognitive impairment, and other symptoms that significantly impair daily functioning.
The researchers conducted a prospective, randomized, double-blind, placebo-controlled trial to evaluate the efficacy of CoQ10 plus NADH supplementation in individuals with ME/CFS. Participants were randomly assigned to receive either CoQ10 plus NADH or placebo for a specified duration, and various outcome measures, including fatigue perception and health-related quality of life, were assessed before and after supplementation.
Full article on https://www.mdpi.com/2072-6643/13/8/2658
Castro-Marrero, J., Sáez-Francàs, N., Segundo, M. J., Calvo, N., Faro, M., Aliste, L., Fernández de Sevilla, T., & Alegre, J. (2016). Effect of coenzyme Q10 plus nicotinamide adenine dinucleotide supplementation on maximum heart rate after exercise testing in chronic fatigue syndrome – A randomized, controlled, double-blind trial. Clinical nutrition (Edinburgh, Scotland), 35(4), 826–834. https://doi.org/10.1016/j.clnu.2015.07.010.
Effect of coenzyme Q10 plus nicotinamide adenine dinucleotide supplementation on maximum heart rate after exercise testing in chronic fatigue syndrome – A randomized, controlled, double-blind trial
In their study, Castro-Marrero et al. (2016) investigate the effect of supplementation with coenzyme Q10 (CoQ10) plus nicotinamide adenine dinucleotide (NADH) on maximum heart rate after exercise testing in individuals with chronic fatigue syndrome (CFS). CFS is a debilitating condition characterized by persistent fatigue, post-exertional malaise, and other symptoms that significantly impact daily functioning.
The researchers conducted a randomized, controlled, double-blind trial to assess the impact of CoQ10 plus NADH supplementation on maximum heart rate following exercise testing in individuals with CFS. Participants were randomly assigned to receive either CoQ10 plus NADH or placebo for a specified duration, and their maximum heart rates during exercise testing were measured before and after supplementation.
Full article on https://www.sciencedirect.com/science/article/pii/S0261561415001892
Castro-Marrero, J., Cordero, M. D., Segundo, M. J., Sáez-Francàs, N., Calvo, N., Román-Malo, L., Aliste, L., Fernández de Sevilla, T., & Alegre, J. (2015). Does oral coenzyme Q10 plus NADH supplementation improve fatigue and biochemical parameters in chronic fatigue syndrome?. Antioxidants & redox signaling, 22(8), 679–685. https://doi.org/10.1089/ars.2014.6181.
Does oral coenzyme Q10 plus NADH supplementation improve fatigue and biochemical parameters in chronic fatigue syndrome?
In their study, Castro-Marrero et al. (2015) aimed to investigate the potential benefits of oral supplementation with coenzyme Q10 (CoQ10) plus nicotinamide adenine dinucleotide (NADH) on fatigue and biochemical parameters in individuals with chronic fatigue syndrome (CFS). CFS is a debilitating condition characterized by persistent fatigue, cognitive dysfunction, and other symptoms that significantly impact daily functioning.
The researchers conducted a clinical trial to assess the effects of CoQ10 plus NADH supplementation on fatigue severity and various biochemical parameters in individuals with CFS. Participants were randomly assigned to receive either CoQ10 plus NADH or placebo for a specified duration, and various outcome measures were assessed before and after supplementation.
The results of the study suggest that oral supplementation with CoQ10 plus NADH may lead to improvements in fatigue severity and certain biochemical parameters in individuals with CFS. Participants who received CoQ10 plus NADH showed reductions in fatigue severity scores compared to those who received placebo, indicating a potential alleviation of symptoms.
Full article on https://www.liebertpub.com/doi/abs/10.1089/ars.2014.6181
Mach, J., Midgley, A. W., Dank, S., Grant, R. S., & Bentley, D. J. (2010). The effect of antioxidant supplementation on fatigue during exercise: potential role for NAD+(H). Nutrients, 2(3), 319–329. https://doi.org/10.3390/nu2030319.
The Effect of Antioxidant Supplementation on Fatigue during Exercise: Potential Role for NAD+(H)
In their study, Mach et al. (2010) explored the potential role of antioxidant supplementation, particularly nicotinamide adenine dinucleotide (NAD^+(H)), in mitigating fatigue during exercise. Fatigue during exercise can stem from various factors, including oxidative stress, which can compromise cellular function and energy production.
The researchers conducted a study to investigate whether antioxidant supplementation, with a focus on NAD^+(H), could influence fatigue levels during exercise. Participants were provided with antioxidant supplements containing NAD^+(H) or a placebo before engaging in exercise sessions. The effects of supplementation on fatigue perception and exercise performance were then evaluated.
Full article on https://www.mdpi.com/2072-6643/2/3/319
Santaella, M. L., Font, I., & Disdier, O. M. (2004). Comparison of oral nicotinamide adenine dinucleotide (NADH) versus conventional therapy for chronic fatigue syndrome. Puerto Rico health sciences journal, 23(2), 89–93.
Comparison of oral nicotinamide adenine dinucleotide (NADH) versus conventional therapy for chronic fatigue syndrome
In their study, Santaella, Font, and Disdier (2004) aimed to compare the effectiveness of oral nicotinamide adenine dinucleotide (NADH) supplementation with conventional therapy for chronic fatigue syndrome (CFS). Chronic fatigue syndrome is a complex disorder characterized by persistent and unexplained fatigue that significantly impairs daily functioning.
The researchers conducted a clinical trial involving individuals diagnosed with CFS, who were randomly assigned to receive either oral NADH supplementation or conventional therapy for a specified duration. The efficacy of each treatment approach was assessed based on various outcome measures, including fatigue severity, overall symptomatology, and functional impairment.
The results of the study suggest that oral NADH supplementation may be beneficial in alleviating symptoms and improving functional capacity in individuals with CFS. Participants who received NADH supplementation reported reductions in fatigue severity and overall symptomatology compared to those who underwent conventional therapy alone. Additionally, NADH supplementation was associated with improvements in functional impairment, indicating enhanced ability to perform daily activities.
Full article on https://prhsj.rcm.upr.edu/index.php/prhsj/article/viewFile/426/312
Stein LR, Imai S. The dynamic regulation of NAD metabolism in mitochondria. Trends EndocrinolMetab. 2012;23(9):420-428. doi:10.1016/j.tem.2012.06.005.
The dynamic regulation of NAD metabolism in mitochondria
In their review article, Stein and Imai (2012) provide insights into the dynamic regulation of nicotinamide adenine dinucleotide (NAD) metabolism within mitochondria, focusing on its significance in cellular physiology and metabolic homeostasis. NAD is a crucial coenzyme involved in various metabolic processes, including energy production, redox reactions, and gene expression regulation.
The authors discuss the importance of NAD metabolism in maintaining mitochondrial function and cellular health. Mitochondria play a central role in energy production through oxidative phosphorylation, where NAD is essential for the electron transport chain and ATP synthesis. Additionally, NAD serves as a substrate for various enzymes, including sirtuins, which regulate cellular processes such as gene expression, DNA repair, and apoptosis.
The review highlights the dynamic regulation of NAD levels within mitochondria, which can be influenced by factors such as nutrient availability, cellular stress, and aging. Alterations in NAD metabolism have been implicated in various age-related diseases, including metabolic disorders, neurodegenerative diseases, and cancer.
Full article on https://www.cell.com/trends/endocrinology-metabolism/fulltext/S1043-2760(12)00106-3
Garten A, Schuster S, Penke M, Gorski T, de Giorgis T, Kiess W. Physiological and pathophysiological roles of NAMPT and NAD metabolism. Nat Rev Endocrinol. 2015;11(9):535-546. doi:10.1038/nrendo.2015.117.
Physiological and pathophysiological roles of NAMPT and NAD metabolism
In their review published in Nature Reviews Endocrinology, Garten et al. (2015) explore the physiological and pathophysiological roles of nicotinamide phosphoribosyltransferase (NAMPT) and nicotinamide adenine dinucleotide (NAD) metabolism. NAD is a crucial cofactor involved in various cellular processes, including energy metabolism, DNA repair, and gene expression regulation.
The authors discuss the multifaceted roles of NAMPT, the rate-limiting enzyme in the salvage pathway of NAD synthesis. NAMPT catalyzes the conversion of nicotinamide (NAM) to nicotinamide mononucleotide (NMN), a key step in NAD biosynthesis. They highlight the importance of NAMPT-mediated NAD synthesis in maintaining cellular redox balance, mitochondrial function, and metabolic homeostasis.
Garten et al. delve into the diverse functions of NAD-dependent enzymes, including sirtuins, poly(ADP-ribose) polymerases (PARPs), and cyclic ADP-ribose synthases (CD38 and CD157), in regulating cellular processes such as transcription, DNA repair, and calcium signaling. They discuss how alterations in NAD metabolism and dysregulation of NAD-dependent pathways contribute to the pathogenesis of various diseases, including metabolic disorders, neurodegenerative diseases, cancer, and aging.
Full article on https://www.nature.com/articles/nrendo.2015.117
Uddin GM, Youngson NA, Sinclair DA, Morris MJ. Head to Head Comparison of Short-Term Treatment with the NAD(+) Precursor Nicotinamide Mononucleotide (NMN) and 6 Weeks of Exercise in Obese Female Mice. Front Pharmacol. 2016;7:258. Published 2016 Aug 19. doi:10.3389/fphar.2016.00258.
Head to Head Comparison of Short-Term Treatment with the NAD(+) Precursor Nicotinamide Mononucleotide (NMN) and 6 Weeks of Exercise in Obese Female Mice
In their study published in Frontiers in Pharmacology, Uddin et al. (2016) conducted a head-to-head comparison of the effects of short-term treatment with the nicotinamide mononucleotide (NMN), a precursor of nicotinamide adenine dinucleotide (NAD+), and 6 weeks of exercise in obese female mice. NAD+ is a crucial cofactor involved in cellular metabolism and energy production, and its levels decline with aging and metabolic disorders.
The researchers aimed to investigate whether NMN supplementation could mimic the metabolic benefits of exercise in obese mice. They compared the effects of NMN treatment with those of exercise on body weight, fat mass, glucose metabolism, insulin sensitivity, and mitochondrial function.
The study found that both NMN supplementation and exercise resulted in improvements in body weight, fat mass, glucose metabolism, and insulin sensitivity in obese female mice. Additionally, both interventions increased mitochondrial oxidative capacity and biogenesis in skeletal muscle.
Full article on https://www.frontiersin.org/articles/10.3389/fphar.2016.00258/full
Rappou E, Jukarainen S, Rinnankoski-Tuikka R et al (2016) Weight loss is associated with increased NAD+/SIRT1 expression but reduced PARP activity in white adipose tissue. J ClinEndocrinolMetab 101(3):1263–1273. https://doi.org/10.1210/jc.2015-3054.
Weight Loss Is Associated With Increased NAD+/SIRT1 Expression But Reduced PARP Activity in White Adipose Tissue
In a study published in the Journal of Clinical Endocrinology & Metabolism, Rappou et al. (2016) investigated the effects of weight loss on the expression of nicotinamide adenine dinucleotide (NAD+) and its associated enzymes in white adipose tissue (WAT).
The researchers aimed to understand how weight loss influences the NAD+/SIRT1 pathway and poly(ADP-ribose) polymerase (PARP) activity in WAT, given the importance of these pathways in regulating metabolism and cellular stress responses.
They conducted their study on obese individuals who underwent either bariatric surgery-induced weight loss or lifestyle intervention-based weight loss. Adipose tissue samples were collected before and after weight loss interventions, and various molecular analyses were performed.
Full article on https://academic.oup.com/jcem/article-abstract/101/3/1263/2804942
Cantó C, Houtkooper RH, Pirinen E, et al. The NAD(+) precursor nicotinamideriboside enhances oxidative metabolism and protects against high-fat diet-induced obesity. Cell Metab. 2012;15(6):838-847. doi:10.1016/j.cmet.2012.04.022.
The NAD(+) precursor nicotinamideriboside enhances oxidative metabolism and protects against high-fat diet-induced obesity
The study titled “The NAD(+) precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity” by Cantó et al. investigated the effects of nicotinamide riboside (NR) supplementation on oxidative metabolism and obesity induced by a high-fat diet.
The researchers conducted experiments using mice fed a high-fat diet supplemented with NR. They observed that NR supplementation increased nicotinamide adenine dinucleotide (NAD+) levels in various tissues, including skeletal muscle and liver. This increase in NAD+ levels was associated with enhanced oxidative metabolism, as evidenced by increased expression of genes involved in mitochondrial biogenesis and function, as well as improved metabolic flexibility.
Full article on https://www.cell.com/fulltext/S1550-4131(12)00192-1
Crisol BM, Veiga CB, Lenhare L, et al. Nicotinamideriboside induces a thermogenic response in lean mice. Life Sci. 2018;211:1-7. doi:10.1016/j.lfs.2018.09.015.
Nicotinamideriboside induces a thermogenic response in lean mice
The study conducted by Crisol et al., titled “Nicotinamide riboside induces a thermogenic response in lean mice,” investigated the effects of nicotinamide riboside (NR) supplementation on thermogenesis in lean mice.
In this study, lean mice were administered NR orally, and various parameters related to thermogenesis and energy metabolism were evaluated. The researchers found that NR supplementation induced a thermogenic response in the mice, as evidenced by an increase in core body temperature. This thermogenic effect was accompanied by increased expression of genes involved in brown adipose tissue (BAT) activation and mitochondrial biogenesis, indicating enhanced energy expenditure and fat oxidation.
Furthermore, NR supplementation led to improved glucose tolerance and insulin sensitivity in the mice, suggesting potential metabolic benefits beyond thermogenesis. These findings highlight the role of NR in promoting energy metabolism and metabolic health in lean mice.
Full article on https://www.sciencedirect.com/science/article/pii/S0024320518305605
Jukarainen S, Heinonen S, Rämö JT, et al. Obesity Is Associated With Low NAD(+)/SIRT Pathway Expression in Adipose Tissue of BMI-Discordant Monozygotic Twins. J ClinEndocrinolMetab. 2016;101(1):275-283. doi:10.1210/jc.2015-3095.
Obesity Is Associated With Low NAD+/SIRT Pathway Expression in Adipose Tissue of BMI-Discordant Monozygotic Twins
The study by Jukarainen et al., titled “Obesity Is Associated With Low NAD(+)/SIRT Pathway Expression in Adipose Tissue of BMI-Discordant Monozygotic Twins,” investigated the expression levels of the NAD(+)/SIRT pathway in adipose tissue of monozygotic twins who were discordant for body mass index (BMI).
In this study, the researchers compared the expression levels of genes related to the NAD(+)/SIRT pathway in adipose tissue samples obtained from BMI-discordant monozygotic twins. They found that twins with obesity had lower expression levels of genes involved in the NAD(+)/SIRT pathway compared to their lean counterparts. Specifically, they observed decreased expression of nicotinamide phosphoribosyltransferase (NAMPT), an enzyme involved in NAD(+) biosynthesis, as well as reduced expression of sirtuin 1 (SIRT1), a key regulator of cellular metabolism and energy homeostasis.
Full article on https://academic.oup.com/jcem/article-abstract/101/1/275/2806840
Yamaguchi S, Yoshino J. Adipose tissue NAD+ biology in obesity and insulin resistance: From mechanism to therapy. Bioessays. 2017;39(5):10.1002/bies.201600227. doi:10.1002/bies.201600227.
Adipose tissue NAD+ biology in obesity and insulin resistance: From mechanism to therapy
In the article “Adipose tissue NAD+ biology in obesity and insulin resistance: From mechanism to therapy” by Yamaguchi and Yoshino, the authors delve into the intricate relationship between adipose tissue NAD(+) levels, obesity, and insulin resistance, offering insights into potential therapeutic avenues.
They elucidate how dysregulation of NAD(+) metabolism in adipose tissue can contribute to the pathogenesis of obesity and insulin resistance. Specifically, they discuss the role of NAD(+) in regulating key metabolic processes such as mitochondrial function, adipogenesis, and inflammation.
The authors highlight the importance of nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in the NAD(+) salvage pathway, in maintaining NAD(+) levels and metabolic homeostasis in adipose tissue. They also explore the impact of NAD(+) precursors, such as nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), on adipose tissue metabolism and insulin sensitivity.
Full article on https://onlinelibrary.wiley.com/doi/abs/10.1002/bies.201600227
Yoshino J, Mills KF, Yoon MJ, Imai S. Nicotinamide mononucleotide, a key NAD (+) intermediate, treats the pathophysiology of diet- and age-induced diabetes in mice. Cell Metab. 2011;14(4):528–536. doi: 10.1016/j.cmet.2011.08.014.
Nicotinamide mononucleotide, a key NAD (+) intermediate, treats the pathophysiology of diet- and age-induced diabetes in mice
In their study published in Cell Metabolism in 2011, Yoshino et al. investigated the therapeutic potential of nicotinamide mononucleotide (NMN), a key intermediate in the NAD(+) biosynthesis pathway, in treating diet- and age-induced diabetes in mice.
The researchers conducted experiments on both diet-induced obese (DIO) mice and aged mice to assess the efficacy of NMN supplementation in improving glucose tolerance, insulin sensitivity, and other metabolic parameters associated with diabetes.
Their findings revealed that NMN administration effectively mitigated diet-induced obesity, improved glucose tolerance, and enhanced insulin sensitivity in DIO mice. Similarly, NMN supplementation ameliorated age-induced glucose intolerance and insulin resistance in aged mice.
Full article on https://www.cell.com/cell-metabolism/pdf/S1550-4131(11)00346-9.pdf
Trammell SA, Weidemann BJ, Chadda A, Yorek MS, Holmes A, Coppey LJ, Obrosov A, Kardon RH, Yorek MA, Brenner C. Nicotinamideriboside opposes type 2 diabetes and neuropathy in mice. Sci Rep. 2016;6:26933. doi: 10.1038/srep26933.
Nicotinamide riboside opposes type 2 diabetes and neuropathy in mice
In their 2016 study published in Scientific Reports, Trammell et al. investigated the potential therapeutic effects of nicotinamide riboside (NR), a precursor of nicotinamide adenine dinucleotide (NAD(+)), in opposing type 2 diabetes and diabetic neuropathy in mice.
The researchers conducted experiments using a mouse model of type 2 diabetes induced by a high-fat diet and low-dose streptozotocin. They administered NR to the diabetic mice via drinking water and evaluated its impact on various metabolic parameters and neuropathic complications associated with diabetes.
Their findings demonstrated that NR supplementation effectively improved glucose tolerance, insulin sensitivity, and glycemic control in diabetic mice. Additionally, NR-treated diabetic mice exhibited reduced levels of systemic inflammation and oxidative stress, as evidenced by decreased levels of pro-inflammatory cytokines and lipid peroxidation markers.
Full article on https://www.nature.com/articles/srep26933
Frederick DW, Davis JG, Davila A, Jr, Agarwal B, Michan S, Puchowicz MA, Nakamaru-Ogiso E, Baur JA. Increasing NAD synthesis in muscle via nicotinamidephosphoribosyltransferase is not sufficient to promote oxidative metabolism. J Biol Chem. 2015;290(3):1546–1558. doi: 10.1074/jbc.M114.579565.
Increasing NAD synthesis in muscle via nicotinamidephosphoribosyltransferase is not sufficient to promote oxidative metabolism
In their 2015 study published in the Journal of Biological Chemistry, Frederick et al. investigated the effects of increasing nicotinamide adenine dinucleotide (NAD) synthesis in muscle through nicotinamide phosphoribosyltransferase (NAMPT) overexpression on oxidative metabolism.
The researchers conducted experiments using transgenic mice with muscle-specific overexpression of NAMPT, the rate-limiting enzyme in the NAD salvage pathway. They examined the impact of NAMPT overexpression on mitochondrial function, oxidative metabolism, and metabolic adaptation in muscle tissue.
Contrary to expectations, the study findings revealed that increasing NAD synthesis via NAMPT overexpression in muscle did not promote oxidative metabolism or mitochondrial biogenesis. Despite elevated NAD levels, the NAMPT-overexpressing mice exhibited impaired mitochondrial function, reduced mitochondrial DNA content, and diminished expression of genes involved in mitochondrial biogenesis and oxidative metabolism.
Full article on https://www.jbc.org/article/S0021-9258(20)57813-7/abstract
Sasaki T, Kikuchi O, Shimpuku M, Susanti VY, Yokota-Hashimoto H, Taguchi R, Shibusawa N, Sato T, et al. Hypothalamic SIRT1 prevents age-associated weight gain by improving leptin sensitivity in mice. Diabetologia. 2014;57(4):819–831. doi: 10.1007/s00125-013-3140-5.
Hypothalamic SIRT1 prevents age-associated weight gain by improving leptin sensitivity in mice
In their 2014 study published in Diabetologia, Sasaki et al. investigated the role of hypothalamic SIRT1 in preventing age-associated weight gain by improving leptin sensitivity in mice.
The researchers focused on SIRT1, a protein involved in various cellular processes including metabolism, aging, and energy homeostasis. They hypothesized that SIRT1 in the hypothalamus, a key brain region regulating energy balance, might play a role in age-related changes in body weight and metabolism.
To test their hypothesis, the researchers conducted experiments using mice with specific deletion of SIRT1 in the hypothalamus. They assessed the effects of hypothalamic SIRT1 deletion on age-associated changes in body weight, energy expenditure, food intake, and leptin sensitivity.
Full article on https://link.springer.com/article/10.1007/s00125-013-3140-5
Yamaguchi S, Franczyk MP, Chondronikola M, et al. Adipose tissue NAD+ biosynthesis is required for regulating adaptive thermogenesis and whole-body energy homeostasis in mice. ProcNatlAcadSci U S A. 2019;116(47):23822-23828. doi:10.1073/pnas.1909917116.
Adipose tissue NAD+ biosynthesis is required for regulating adaptive thermogenesis and whole-body energy homeostasis in mice
In their 2019 study published in the Proceedings of the National Academy of Sciences of the United States of America (PNAS), Yamaguchi et al. investigated the role of adipose tissue NAD+ biosynthesis in regulating adaptive thermogenesis and whole-body energy homeostasis in mice.
The researchers focused on NAD+ biosynthesis, a critical process involved in cellular metabolism and energy production. They hypothesized that NAD+ biosynthesis in adipose tissue might play a role in regulating adaptive thermogenesis, a process by which the body generates heat in response to cold or excess energy intake.
To test their hypothesis, the researchers utilized genetically modified mice with adipose tissue-specific deletion of an enzyme involved in NAD+ biosynthesis, namely nicotinamide phosphoribosyltransferase (Nampt). They compared these mice with control mice under various experimental conditions, including exposure to cold temperatures and high-fat diet feeding.
Full article on https://www.pnas.org/doi/abs/10.1073/pnas.1909917116
Mills, K. F., Yoshida, S., Stein, L. R., Grozio, A., Kubota, S., Sasaki, Y., et al. (2016). Long-term administration of nicotinamide mononucleotide mitigates age-associated physiological decline in mice. Cell Metab. 24, 795–806. doi: 10.1016/j.cmet.2016.09.013.
Long-term administration of nicotinamide mononucleotide mitigates age-associated physiological decline in mice
In their 2016 study published in Cell Metabolism, Mills et al. investigated the effects of long-term administration of nicotinamide mononucleotide (NMN) on age-associated physiological decline in mice.
The researchers aimed to determine whether NMN supplementation could mitigate age-related physiological decline by enhancing NAD+ metabolism, which plays a critical role in cellular energy production and metabolism.
To conduct their study, the researchers administered NMN to mice through their drinking water starting at 5 months of age and continued the supplementation for up to 12 months. They then assessed various physiological parameters in the NMN-treated mice compared to control mice that did not receive NMN supplementation.
Full article on https://www.cell.com/cell-metabolism/pdf/S1550-4131(16)30495-8.pdf
Cantó, C., Houtkooper, R. H., Pirinen, E., Youn, D. Y., Oosterveer, M. H., Cen, Y., Fernandez-Marcos, P. J., Yamamoto, H., Andreux, P. A., Cettour-Rose, P., Gademann, K., Rinsch, C., Schoonjans, K., Sauve, A. A., & Auwerx, J. (2012). The NAD(+) precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity. Cell metabolism, 15(6), 838–847. https://doi.org/10.1016/j.cmet.2012.04.022.
The NAD+ precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity
In their 2012 study published in Cell Metabolism, Cantó et al. investigated the effects of nicotinamide riboside (NR), a precursor of nicotinamide adenine dinucleotide (NAD+), on oxidative metabolism and obesity induced by a high-fat diet.
The researchers aimed to determine whether NR supplementation could enhance oxidative metabolism and protect against obesity in mice fed a high-fat diet, which is known to induce metabolic dysfunction and obesity.
To conduct their study, the researchers administered NR to mice in their drinking water for several weeks and then assessed various metabolic parameters in the NR-treated mice compared to control mice that did not receive NR supplementation.
Full article on https://www.cell.com/fulltext/S1550-4131(12)00192-1
Gomes, A. P., Price, N. L., Ling, A. J., Moslehi, J. J., Montgomery, M. K., Rajman, L., White, J. P., Teodoro, J. S., Wrann, C. D., Hubbard, B. P., Mercken, E. M., Palmeira, C. M., de Cabo, R., Rolo, A. P., Turner, N., Bell, E. L., & Sinclair, D. A. (2013). Declining NAD(+) induces a pseudohypoxic state disrupting nuclear-mitochondrial communication during aging. Cell, 155(7), 1624–1638. https://doi.org/10.1016/j.cell.2013.11.037.
Declining NAD+ induces a pseudohypoxic state disrupting nuclear-mitochondrial communication during aging
In their 2013 study published in Cell, Gomes et al. investigated the role of declining nicotinamide adenine dinucleotide (NAD+) levels in the aging process, particularly its impact on nuclear-mitochondrial communication and cellular metabolism.
The researchers aimed to understand how declining NAD+ levels contribute to age-related physiological decline and dysfunction. They hypothesized that decreased NAD+ availability disrupts the balance between nuclear and mitochondrial functions, leading to a “pseudohypoxic” state resembling cellular responses to low oxygen levels.
To investigate this hypothesis, the researchers conducted experiments using various cell culture models and mouse models with altered NAD+ levels. They measured cellular oxygen consumption rates, gene expression patterns, and metabolic parameters to assess the effects of NAD+ depletion on cellular metabolism and mitochondrial function.
Full article on https://www.cell.com/fulltext/S1550-4131(12)00192-1
Yaku K, Okabe K, Hikosaka K, Nakagawa T. NAD Metabolism in Cancer Therapeutics. Front Oncol. 2018;8:622. Published 2018 Dec 12. doi:10.3389/fonc.2018.00622.
NAD Metabolism in Cancer Therapeutics
In their 2018 review published in Frontiers in Oncology, Yaku et al. explored the intricate relationship between nicotinamide adenine dinucleotide (NAD+) metabolism and cancer therapeutics. They discussed how cancer cells exhibit alterations in NAD+ metabolism, including changes in biosynthesis, consumption, and compartmentalization, which contribute to their proliferation, survival, and metastasis. The authors highlighted the role of NAD+-consuming enzymes such as PARPs and sirtuins in cancer development and progression, and they discussed therapeutic strategies targeting NAD+ metabolism, including inhibition of biosynthesis and modulation of NAD+-consuming enzymes. These approaches aim to exploit the vulnerabilities of cancer cells related to their altered NAD+ metabolism, offering potential opportunities for novel cancer therapies. The review also discussed the clinical implications of targeting NAD+ metabolism, showcasing the potential of compounds like PARP inhibitors and sirtuin modulators in preclinical and clinical cancer studies.
Full article on https://www.frontiersin.org/articles/10.3389/fonc.2018.00622/full
Lewis JE, Singh N, Holmila RJ, et al. Targeting NAD+ Metabolism to Enhance Radiation Therapy Responses. SeminRadiatOncol. 2019;29(1):6-15. doi:10.1016/j.semradonc.2018.10.009.
Targeting NAD+ Metabolism to Enhance Radiation Therapy Responses
In their 2019 article published in Seminars in Radiation Oncology, Lewis et al. delved into the potential of targeting nicotinamide adenine dinucleotide (NAD+) metabolism to augment responses to radiation therapy. The authors explored the intricate interplay between NAD+ metabolism and the cellular response to radiation, emphasizing how alterations in NAD+ levels impact DNA repair mechanisms, cell survival pathways, and tumor microenvironment dynamics. They discussed various strategies aimed at modulating NAD+ metabolism, such as targeting NAD+ biosynthesis pathways, inhibiting NAD+-consuming enzymes like PARPs, and enhancing NAD+ salvage pathways. Through a comprehensive review of preclinical studies and clinical trials, the authors highlighted the promising therapeutic potential of combining radiation therapy with NAD+ metabolism-targeting agents to improve treatment outcomes for cancer patients.
Full article on https://www.sciencedirect.com/science/article/pii/S1053429618300900
Djouder N. Boosting NAD(+) for the prevention and treatment of liver cancer. Mol Cell Oncol. 2015;2(4):e1001199. Published 2015 Feb 3. doi:10.1080/23723556.2014.1001199.
Boosting NAD+ for the prevention and treatment of liver cancer
In the 2015 article published in Molecular and Cellular Oncology, Djouder explored the potential of boosting nicotinamide adenine dinucleotide (NAD+) levels for the prevention and treatment of liver cancer. The author discussed how dysregulation of NAD+ metabolism contributes to the pathogenesis of liver cancer, highlighting its role in maintaining cellular homeostasis, regulating energy metabolism, and modulating various signaling pathways involved in cancer progression. Djouder also reviewed preclinical studies demonstrating the efficacy of NAD+-boosting interventions, such as supplementation with NAD+ precursors or inhibition of NAD+-consuming enzymes, in suppressing liver tumorigenesis and improving therapeutic responses. By shedding light on the intricate interplay between NAD+ metabolism and liver cancer biology, the article provided valuable insights into the development of novel preventive and therapeutic strategies targeting this metabolic pathway.
Full article on https://www.tandfonline.com/doi/abs/10.1080/23723556.2014.1001199
Elhassan YS, Kluckova K, Fletcher RS, et al. NicotinamideRiboside Augments the Aged Human Skeletal Muscle NAD+ Metabolome and Induces Transcriptomic and Anti-inflammatory Signatures. Cell Rep. 2019;28(7):1717-1728.e6. doi:10.1016/j.celrep.2019.07.043.
NicotinamideRiboside Augments the Aged Human Skeletal Muscle NAD+ Metabolome and Induces Transcriptomic and Anti-inflammatory Signatures
In their 2019 study published in Cell Reports, Elhassan and colleagues investigated the effects of nicotinamide riboside (NR) supplementation on the aged human skeletal muscle nicotinamide adenine dinucleotide (NAD+) metabolome and its associated transcriptomic and anti-inflammatory signatures. Through a randomized controlled trial involving older adults, the researchers demonstrated that NR supplementation augmented the NAD+ metabolome in skeletal muscle tissue. Furthermore, NR treatment induced transcriptomic changes indicative of improved mitochondrial function and anti-inflammatory responses in skeletal muscle. These findings suggest that NR supplementation holds promise as a potential intervention to counteract age-related declines in skeletal muscle function and promote overall health in older individuals.
Full article on https://www.cell.com/cell-reports/pdf/S2211-1247(19)30940-4.pdf
Mendelsohn AR, Larrick JW. Partial reversal of skeletal muscle aging by restoration of normal NAD⁺ levels. Rejuvenation Res. 2014;17(1):62-69. doi:10.1089/rej.2014.1546.
Partial reversal of skeletal muscle aging by restoration of normal NAD⁺ levels
In their 2014 study published in Rejuvenation Research, Mendelsohn and Larrick investigated the potential of restoring normal nicotinamide adenine dinucleotide (NAD⁺) levels to partially reverse skeletal muscle aging. They examined the effects of NAD⁺ supplementation on age-related declines in skeletal muscle function. Their findings suggested that restoring normal NAD⁺ levels could partially reverse some aspects of skeletal muscle aging, indicating a potential therapeutic approach for mitigating age-related muscle decline.
Full article on https://www.liebertpub.com/doi/abs/10.1089/rej.2014.1546
Goody MF, Henry CA. A need for NAD+ in muscle development, homeostasis, and aging. Skelet Muscle. 2018;8(1):9. Published 2018 Mar 7. doi:10.1186/s13395-018-0154-1.
A need for NAD+ in muscle development, homeostasis, and aging
In their 2018 review published in Skeletal Muscle, Goody and Henry underscored the essential role of nicotinamide adenine dinucleotide (NAD⁺) in muscle development, homeostasis, and aging. They discussed the importance of NAD⁺ as a coenzyme involved in various cellular processes critical for muscle function, including energy metabolism, mitochondrial biogenesis, and stress response pathways. Additionally, they highlighted emerging evidence suggesting that dysregulation of NAD⁺ metabolism may contribute to age-related muscle decline and proposed NAD⁺ supplementation as a potential strategy to promote muscle health and combat aging-related muscle dysfunction.
Full article on https://skeletalmusclejournal.biomedcentral.com/articles/10.1186/s13395-018-0154-1
Lautrup, S., Sinclair, D. A., Mattson, M. P., & Fang, E. F. (2019). NAD+ in Brain Aging and Neurodegenerative Disorders. Cell metabolism, 30(4), 630–655. https://doi.org/10.1016/j.cmet.2019.09.001.
NAD+ in Brain Aging and Neurodegenerative Disorders
In their comprehensive review published in Cell Metabolism in 2019, Lautrup et al. explored the role of nicotinamide adenine dinucleotide (NAD⁺) in brain aging and neurodegenerative disorders. The authors discussed how NAD⁺ levels decline with age and how this decline contributes to various aspects of brain aging, including mitochondrial dysfunction, oxidative stress, impaired DNA repair, and dysregulated calcium homeostasis. They also examined the potential therapeutic implications of boosting NAD⁺ levels through supplementation or activation of NAD⁺-dependent enzymes, such as sirtuins and PARPs, in mitigating age-related cognitive decline and neurodegenerative diseases like Alzheimer’s and Parkinson’s. Additionally, the review highlighted ongoing research efforts aimed at understanding the mechanisms underlying NAD⁺ metabolism in the brain and its impact on neuronal function and survival.
Full article on https://www.cell.com/cell-metabolism/pdf/S1550-4131(19)30502-9.pdf
Mao, K., & Zhang, G. (2022). The role of PARP1 in neurodegenerative diseases and aging. The FEBS journal, 289(8), 2013–2024. https://doi.org/10.1111/febs.15716.
The role of PARP1 in neurodegenerative diseases and aging
In their article published in The FEBS Journal in 2022, Mao and Zhang explored the role of poly(ADP-ribose) polymerase 1 (PARP1) in neurodegenerative diseases and aging. The authors discussed how PARP1, a nuclear enzyme involved in DNA repair and transcriptional regulation, is implicated in various neurodegenerative conditions, including Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. They reviewed evidence suggesting that PARP1 activation contributes to neuronal dysfunction and death through multiple mechanisms, including DNA damage accumulation, mitochondrial dysfunction, inflammation, and impaired autophagy. Additionally, the authors discussed the potential therapeutic strategies targeting PARP1 in these diseases, highlighting PARP inhibitors as promising candidates for intervention. Overall, the article provides insights into the multifaceted roles of PARP1 in neurodegeneration and aging, emphasizing its potential as a therapeutic target for mitigating age-related neurodegenerative disorders.
Full article on https://febs.onlinelibrary.wiley.com/doi/abs/10.1111/febs.15716
Ying W. (2007). NAD+ and NADH in brain functions, brain diseases and brain aging. Frontiers in bioscience: a journal and virtual library, 12, 1863–1888. https://doi.org/10.2741/2194.
NAD+ and NADH in brain functions, brain diseases and brain aging
In the 2007 article “NAD+ and NADH in brain functions, brain diseases, and brain aging” published in Frontiers in Bioscience, Ying delves into the crucial roles of nicotinamide adenine dinucleotide (NAD+) and its reduced form, NADH, in various aspects of brain function, pathology, and aging. The author comprehensively discusses the involvement of NAD+ and NADH in energy metabolism, redox reactions, and signaling pathways within the brain. Moreover, the article explores the implications of dysregulated NAD+ metabolism in neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease, as well as in brain aging processes. By examining the molecular mechanisms underlying NAD+ and NADH actions, Ying sheds light on their potential as therapeutic targets for addressing brain-related disorders and age-related cognitive decline.
Full article on https://article.imrpress.com/bri/Landmark/articles/pdf/Landmark2194.pdf
Lloret, A., & Beal, M. F. (2019). PGC-1α, Sirtuins and PARPs in Huntington’s Disease and Other Neurodegenerative Conditions: NAD+ to Rule Them All. Neurochemical research, 44(10), 2423–2434. https://doi.org/10.1007/s11064-019-02809-1.
PGC-1α, sirtuins and PARPs in Huntington’s disease and other neurodegenerative conditions: NAD+ to rule them all
In their 2019 paper titled “PGC-1α, Sirtuins, and PARPs in Huntington’s Disease and Other Neurodegenerative Conditions: NAD+ to Rule Them All,” Lloret and Beal explore the roles of PGC-1α, sirtuins, and PARPs in Huntington’s disease (HD) and other neurodegenerative conditions, emphasizing the pivotal role of nicotinamide adenine dinucleotide (NAD+) in these pathways. The authors discuss how dysregulation of these key regulators contributes to mitochondrial dysfunction, oxidative stress, and neuroinflammation observed in HD and other neurodegenerative diseases. They highlight the therapeutic potential of NAD+ augmentation strategies in mitigating disease progression by restoring cellular homeostasis and promoting neuroprotection. This review provides valuable insights into the interconnected pathways involving PGC-1α, sirtuins, and PARPs, underscoring NAD+ as a central player in the pathophysiology and potential treatment of neurodegenerative conditions.
Full article on https://link.springer.com/article/10.1007/s11064-019-02809-1
Yang H, Yang T, Baur JA, et al. Nutrient-sensitive mitochondrial NAD+ levels dictate cell survival. Cell. 2007;130(6):1095-1107. doi:10.1016/j.cell.2007.07.035.
Nutrient-sensitive mitochondrial NAD+ levels dictate cell survival
In their 2007 study published in Cell, titled “Nutrient-sensitive mitochondrial NAD+ levels dictate cell survival,” Yang et al. investigate the role of mitochondrial nicotinamide adenine dinucleotide (NAD+) levels in cell survival. They demonstrate that mitochondrial NAD+ levels play a critical role in determining cell fate under conditions of nutrient deprivation and stress. The researchers show that maintenance of mitochondrial NAD+ levels through nicotinamide phosphoribosyltransferase (NAMPT)-mediated NAD+ biosynthesis is essential for cell survival during energy stress. Furthermore, they highlight the importance of the NAD+-dependent enzyme sirtuin 3 (SIRT3) in protecting cells from metabolic stress-induced apoptosis by promoting mitochondrial function and antioxidant defense. Overall, this study underscores the significance of mitochondrial NAD+ metabolism in cellular responses to nutrient availability and stress, providing insights into potential therapeutic strategies for conditions associated with metabolic dysregulation.
Full article on https://www.cell.com/fulltext/S0092-8674(07)00973-7
Verdin E. NAD⁺ in aging, metabolism, and neurodegeneration. Science. 2015;350(6265):1208-1213. doi:10.1126/science.aac4854.
NAD+ in aging, metabolism, and neurodegeneration
In his 2015 review article published in Science titled “NAD⁺ in aging, metabolism, and neurodegeneration,” Verdin explores the multifaceted roles of nicotinamide adenine dinucleotide (NAD⁺) in various physiological processes. He discusses how NAD⁺ serves as a cofactor for enzymes involved in diverse cellular functions, including metabolism, DNA repair, and gene expression regulation. Verdin highlights emerging evidence implicating NAD⁺ dysregulation in aging-related decline and age-associated diseases, such as neurodegenerative disorders. He further examines the therapeutic potential of targeting NAD⁺ metabolism to ameliorate age-related pathologies, suggesting that interventions aimed at boosting NAD⁺ levels could have beneficial effects on healthspan and lifespan. Overall, this review underscores the importance of NAD⁺ as a central regulator of cellular metabolism and aging processes, providing insights into potential strategies for mitigating age-related decline and disease.
Full article on https://www.science.org/doi/abs/10.1126/science.aac4854
Ying W. NAD+ and NADH in brain functions, brain diseases and brain aging. Front Biosci. 2007;12:1863-1888. Published 2007 Jan 1. doi:10.2741/2194.
NAD+ and NADH in brain functions, brain diseases and brain aging
In the comprehensive review article “NAD+ and NADH in brain functions, brain diseases, and brain aging,” published in Frontiers in Bioscience in 2007, Ying W. delves into the intricate roles of nicotinamide adenine dinucleotide (NAD+) and its reduced form (NADH) in brain physiology and pathology. The review elucidates how NAD+ and NADH serve as crucial cofactors in numerous enzymatic reactions involved in energy metabolism, neurotransmitter synthesis, and antioxidant defense mechanisms within the brain. Furthermore, Ying W. explores the implications of alterations in NAD+ and NADH levels in various neurological disorders, including Alzheimer’s disease, Parkinson’s disease, and ischemic brain injury. The review also discusses the potential impact of NAD+ metabolism on neuronal survival and aging processes in the brain. Overall, this comprehensive review sheds light on the multifaceted roles of NAD+ and NADH in brain function and dysfunction, offering valuable insights into their therapeutic potential for treating brain-related disorders and promoting healthy brain aging.
Full article on https://article.imrpress.com/bri/Landmark/articles/pdf/Landmark2194.pdf
Belenky P, Racette FG, Bogan KL, McClure JM, Smith JS, Brenner C. Nicotinamideriboside promotes Sir2 silencing and extends lifespan via Nrk and Urh1/Pnp1/Meu1 pathways to NAD+. Cell. 2007 May 4;129(3):473-84.
Nicotinamide riboside promotes Sir2 silencing and extends lifespan via Nrk and Urh1/Pnp1/Meu1 pathways to NAD+
In their seminal study published in Cell in 2007, Belenky et al. elucidate the mechanisms underlying the lifespan-extending effects of nicotinamide riboside (NR), a precursor to nicotinamide adenine dinucleotide (NAD+). The study reveals that NR promotes Sir2 silencing, a process associated with increased lifespan, through the Nrk and Urh1/Pnp1/Meu1 pathways, leading to enhanced NAD+ levels. By modulating NAD+ synthesis via these pathways, NR supplementation effectively extends lifespan in yeast models. This research provides critical insights into the molecular pathways involved in NAD+ metabolism and their implications for longevity, paving the way for further investigations into the therapeutic potential of NAD+ precursors in aging-related conditions.
Full article on https://www.cell.com/fulltext/S0092-8674(07)00390-X
Rajman L, Chwalek K, Sinclair DA. Therapeutic Potential of NAD-Boosting Molecules: The In Vivo Evidence. Cell Metab. 2018;27(3):529-547. doi:10.1016/j.cmet.2018.02.011.
Therapeutic Potential of NAD-Boosting Molecules: The In Vivo Evidence
In their comprehensive review published in Cell Metabolism in 2018, Rajman et al. present a compelling analysis of the therapeutic potential of NAD-boosting molecules based on in vivo evidence. The authors delve into the diverse strategies employed to increase cellular NAD+ levels, including supplementation with NAD precursors like nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), as well as activation of NAD+ biosynthetic enzymes. They discuss the various physiological processes influenced by NAD+ levels, such as mitochondrial function, DNA repair, and gene expression regulation, and highlight the role of NAD+ in modulating aging and age-related diseases. Through a meticulous examination of preclinical and clinical studies, the review underscores the promising therapeutic implications of NAD-boosting interventions in combating a wide range of health conditions, from metabolic disorders to neurodegenerative diseases, offering valuable insights into the burgeoning field of NAD+ biology and its translational potential.
Full article on https://www.cell.com/cell-metabolism/pdf/S1550-4131(18)30122-0.pdf
Massudi H, Grant R, Braidy N, Guest J, Farnsworth B, Guillemin GJ. Age-associated changes in oxidative stress and NAD+ metabolism in human tissue. PLoS One. 2012;7(7):e42357. doi:10.1371/journal.pone.0042357.
Age-Associated Changes In Oxidative Stress and NAD+ Metabolism In Human Tissue
In their study published in PLoS One in 2012, Massudi et al. investigate age-associated alterations in oxidative stress and NAD+ metabolism across various human tissues. The researchers examined the levels of oxidative stress markers and NAD+ metabolites in samples from different age groups, aiming to elucidate potential links between these changes and aging. Their findings reveal significant increases in oxidative stress markers and declines in NAD+ levels with advancing age, suggesting a potential interplay between oxidative stress and NAD+ metabolism in the aging process. This study contributes valuable insights into the molecular mechanisms underlying age-related changes in cellular function and highlights the importance of NAD+ metabolism as a potential target for interventions aimed at mitigating age-related decline.
Full article on https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0042357
Braidy N, Liu Y. NAD+ therapy in age-related degenerative disorders: A benefit/risk analysis. ExpGerontol. 2020;132:110831. doi:10.1016/j.exger.2020.110831.
NAD+ therapy in age-related degenerative disorders: A benefit/risk analysis
In their review article published in Experimental Gerontology in 2020, Braidy and Liu conducted a benefit/risk analysis of NAD+ therapy in age-related degenerative disorders. They synthesized existing evidence on the potential benefits and risks of NAD+ supplementation in various age-related conditions, including neurodegenerative diseases, metabolic disorders, and cardiovascular diseases. The authors evaluated the preclinical and clinical studies investigating the efficacy and safety of NAD+ therapy, considering factors such as dosing regimens, treatment duration, and adverse effects. Their analysis provides valuable insights into the therapeutic potential of NAD+ supplementation across different age-related degenerative disorders while highlighting the need for further research to optimize treatment strategies and minimize potential risks.
Full article on https://www.sciencedirect.com/science/article/pii/S0531556519307582
Schultz MB, Sinclair DA. Why NAD(+) Declines during Aging: It’s Destroyed. Cell Metab. 2016;23(6):965-966. doi:10.1016/j.cmet.2016.05.022.
Why NAD(+) Declines during Aging: It’s Destroyed
In their review published in Cell Metabolism in 2016, Schultz and Sinclair explored the mechanisms underlying the decline of NAD+ during aging, proposing that it is primarily due to its degradation. They highlighted the importance of understanding the factors contributing to NAD+ depletion in aging cells and tissues, including increased activity of NAD+-consuming enzymes such as PARPs and sirtuins, as well as decreased NAD+ biosynthesis. The authors discussed how this decline in NAD+ levels can lead to impaired cellular functions and contribute to the development of age-related diseases. Their insights shed light on potential strategies to counteract NAD+ decline and mitigate age-related health decline.
Full article on https://www.cell.com/cell-metabolism/pdf/S1550-4131(16)30244-3.pdf
Yaku K, Okabe K, Nakagawa T. NAD metabolism: Implications in aging and longevity. Ageing Res Rev. 2018;47:1-17. doi:10.1016/j.arr.2018.05.006.
NAD metabolism: Implications in aging and longevity
In their review published in Ageing Research Reviews in 2018, Yaku, Okabe, and Nakagawa discussed the implications of NAD metabolism in aging and longevity. They provided insights into the role of NAD in various cellular processes, including energy metabolism, DNA repair, and gene expression regulation. The authors highlighted the decline in NAD levels during aging and its association with age-related diseases. They also discussed the potential of NAD precursors and NAD-boosting molecules as therapeutic interventions to promote healthy aging and extend lifespan. Their comprehensive review contributes to our understanding of the intricate relationship between NAD metabolism and the aging process.
Full article on https://www.sciencedirect.com/science/article/pii/S1568163718300060
Cantó C, Menzies KJ, Auwerx J. NAD(+) Metabolism and the Control of Energy Homeostasis: A Balancing Act between Mitochondria and the Nucleus. Cell Metab. 2015;22(1):31-53. doi:10.1016/j.cmet.2015.05.023.
NAD(+) Metabolism and the Control of Energy Homeostasis: A Balancing Act between Mitochondria and the Nucleus
In their review published in Cell Metabolism in 2015, Cantó, Menzies, and Auwerx explored the intricate interplay between NAD(+) metabolism and the regulation of energy homeostasis. They discussed how NAD(+) serves as a crucial cofactor in various metabolic pathways, including glycolysis, oxidative phosphorylation, and fatty acid oxidation, thereby influencing cellular energy production. The authors also highlighted the role of NAD(+) in modulating mitochondrial function, biogenesis, and dynamics, as well as its involvement in nuclear processes such as transcriptional regulation and DNA repair. They emphasized the importance of maintaining NAD(+) homeostasis for overall metabolic health and proposed NAD(+) modulation as a potential therapeutic strategy for metabolic disorders. This comprehensive review provides valuable insights into the multifaceted roles of NAD(+) in energy metabolism and its implications for metabolic homeostasis.
Full article on https://www.cell.com/cell-metabolism/pdf/S1550-4131(15)00266-1.pdf
Zhang N, Sauve AA. Regulatory Effects of NAD+ Metabolic Pathways on Sirtuin Activity. ProgMolBiolTransl Sci. 2018;154:71-104. doi:10.1016/bs.pmbts.2017.11.012.
Regulatory effects of NAD+ metabolic pathways on sirtuin activity
In their publication in Progress in Molecular Biology and Translational Science in 2018, Zhang and Sauve delved into the regulatory effects of NAD+ metabolic pathways on sirtuin activity. They discussed how sirtuins, a class of NAD+-dependent protein deacylases, play critical roles in various cellular processes such as metabolism, stress response, and aging. The authors explored the intricate interplay between NAD+ availability and sirtuin function, highlighting how changes in NAD+ levels can modulate sirtuin activity and subsequently impact cellular physiology. They also discussed the regulatory mechanisms governing NAD+ biosynthesis, salvage, and consumption, shedding light on the complex network of pathways that govern cellular NAD+ metabolism. Through their comprehensive review, Zhang and Sauve provided valuable insights into the tight coupling between NAD+ metabolism and sirtuin-mediated signaling, with implications for understanding cellular homeostasis and disease pathogenesis.
Full article on https://www.sciencedirect.com/science/article/pii/S1877117317301904
Connell, N.J., Houtkooper, R.H. &Schrauwen, P. NAD+ metabolism as a target for metabolic health: have we found the silver bullet?.Diabetologia 62, 888–899 (2019). https://doi.org/10.1007/s00125-019-4831-3.
NAD+ metabolism as a target for metabolic health: have we found the silver bullet?
In their review article published in Diabetologia in 2019, Connell et al. examined NAD+ metabolism as a potential target for improving metabolic health, questioning whether it could serve as a “silver bullet” in addressing metabolic disorders. They synthesized findings from various studies exploring the role of NAD+ in cellular metabolism, mitochondrial function, and aging-related processes. The authors discussed how alterations in NAD+ levels and its related pathways are implicated in metabolic diseases such as obesity, type 2 diabetes, and cardiovascular disorders. Additionally, they evaluated emerging therapeutic strategies aimed at modulating NAD+ metabolism, including the use of NAD+ precursors and activators of NAD+-dependent enzymes like sirtuins. Connell and colleagues critically assessed the current state of research in this field, highlighting both the promises and challenges associated with targeting NAD+ metabolism for metabolic health interventions. Their comprehensive review provides valuable insights into the potential of NAD+ modulation as a therapeutic avenue for metabolic disorders.
Full article on https://link.springer.com/article/10.1007/s00125-019-4831-3
Elhassan YS, Philp AA, Lavery GG. Targeting NAD+ in Metabolic Disease: New Insights Into an Old Molecule. J Endocr Soc. 2017;1(7):816-835. Published 2017 May 15. doi:10.1210/js.2017-00092.
Targeting NAD+ in Metabolic Disease: New Insights Into an Old Molecule
In their review article published in the Journal of Endocrine Society in 2017, Elhassan et al. explore the potential of targeting nicotinamide adenine dinucleotide (NAD+) in metabolic diseases, offering new insights into this well-known molecule. The authors delve into the multifaceted roles of NAD+ in cellular metabolism, energy homeostasis, and redox balance, highlighting its importance in various metabolic pathways. They discuss emerging research elucidating the link between NAD+ dysregulation and metabolic disorders such as obesity, type 2 diabetes, and cardiovascular diseases. Furthermore, the review delves into the therapeutic implications of modulating NAD+ levels, including the use of NAD+ precursors and activators of NAD+-dependent enzymes like sirtuins. Elhassan and colleagues provide a comprehensive overview of the current understanding of NAD+ biology in the context of metabolic disease, offering valuable insights into potential therapeutic strategies targeting NAD+ metabolism.
Full article on https://academic.oup.com/jes/article-abstract/1/7/816/3827720
Okabe K, Yaku K, Tobe K, Nakagawa T. Implications of altered NAD metabolism in metabolic disorders. J Biomed Sci. 2019;26(1):34. Published 2019 May 11. doi:10.1186/s12929-019-0527-8.
Implications of altered NAD metabolism in metabolic disorders
In their 2019 publication in the Journal of Biomedical Science, Okabe et al. discuss the implications of altered nicotinamide adenine dinucleotide (NAD) metabolism in metabolic disorders. The authors provide insights into how dysregulation of NAD metabolism contributes to the pathogenesis of various metabolic diseases, including obesity, type 2 diabetes, and cardiovascular disorders. They explore the role of NAD in cellular energy metabolism, mitochondrial function, and regulation of key metabolic pathways such as glycolysis, fatty acid oxidation, and oxidative phosphorylation. Additionally, Okabe and colleagues discuss emerging evidence linking NAD metabolism to cellular stress responses, inflammation, and insulin signaling pathways. By summarizing recent research findings, the authors highlight the potential of targeting NAD metabolism as a therapeutic approach for treating metabolic disorders. Their review provides valuable insights into the complex interplay between NAD metabolism and metabolic health, paving the way for future studies and therapeutic interventions in this field.
Full article on https://jbiomedsci.biomedcentral.com/articles/10.1186/s12929-019-0527-8
Prolla TA, Denu JM. NAD+ deficiency in age-related mitochondrial dysfunction. Cell Metab. 2014;19(2):178-180. doi:10.1016/j.cmet.2014.01.005.
NAD+ deficiency in age-related mitochondrial dysfunction
In their 2014 article published in Cell Metabolism, Prolla and Denu address the role of nicotinamide adenine dinucleotide (NAD+) deficiency in age-related mitochondrial dysfunction. The authors highlight the critical importance of NAD+ in maintaining mitochondrial function and energy metabolism, emphasizing its roles as a coenzyme for various enzymes involved in cellular processes such as glycolysis, the tricarboxylic acid (TCA) cycle, and oxidative phosphorylation. They discuss how NAD+ levels decline with age, leading to impaired mitochondrial function, increased oxidative stress, and reduced energy production. Prolla and Denu also explore potential mechanisms underlying NAD+ depletion in aging, including decreased NAD+ biosynthesis, increased NAD+ consumption by enzymes such as poly(ADP-ribose) polymerases (PARPs) and sirtuins, and altered NAD+ salvage pathways. By elucidating the link between NAD+ deficiency and age-related mitochondrial dysfunction, the authors underscore the importance of NAD+ replenishment strategies as potential interventions to mitigate age-related decline in mitochondrial function and associated pathologies. Their insights contribute to our understanding of the molecular mechanisms underlying aging and hold promise for the development of novel therapeutic approaches targeting NAD+ metabolism to promote healthy aging.
Full article on https://www.cell.com/cell-metabolism/pdf/S1550-4131(14)00011-4.pdf
Seo KS, Kim JH, Min KN, et al. KL1333, a Novel NAD+ Modulator, Improves Energy Metabolism and Mitochondrial Dysfunction in MELAS Fibroblasts. Front Neurol. 2018;9:552. Published 2018 Jul 5. doi:10.3389/fneur.2018.00552.
KL1333, a Novel NAD+ Modulator, Improves Energy Metabolism and Mitochondrial Dysfunction in MELAS Fibroblasts
In their 2018 study published in Frontiers in Neurology, Seo et al. investigated the potential therapeutic effects of KL1333, a novel NAD+ modulator, on energy metabolism and mitochondrial dysfunction in fibroblasts from individuals with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS). MELAS is a mitochondrial disorder characterized by impaired mitochondrial function and energy metabolism. The authors found that treatment with KL1333 improved energy metabolism and mitochondrial function in MELAS fibroblasts, as evidenced by enhanced ATP production, improved mitochondrial membrane potential, and increased mitochondrial respiration rates. Additionally, KL1333 treatment led to a reduction in reactive oxygen species (ROS) levels and improved cellular viability in MELAS fibroblasts. These findings suggest that KL1333 may have therapeutic potential for mitigating mitochondrial dysfunction and associated symptoms in MELAS and other mitochondrial disorders. The study contributes to our understanding of NAD+ modulation as a potential strategy for targeting mitochondrial dysfunction and improving cellular energetics in mitochondrial diseases.
Full article on https://www.frontiersin.org/articles/10.3389/fneur.2018.00552/full
Goody MF, Henry CA. A need for NAD+ in muscle development, homeostasis, and aging. Skelet Muscle. 2018;8(1):9. Published 2018 Mar 7. doi:10.1186/s13395-018-0154-1.
A need for NAD+ in muscle development, homeostasis, and aging
In their 2018 review published in Skeletal Muscle, Goody and Henry underscored the essential role of nicotinamide adenine dinucleotide (NAD⁺) in muscle development, homeostasis, and aging. They discussed the importance of NAD⁺ as a coenzyme involved in various cellular processes critical for muscle function, including energy metabolism, mitochondrial biogenesis, and stress response pathways. Additionally, they highlighted emerging evidence suggesting that dysregulation of NAD⁺ metabolism may contribute to age-related muscle decline and proposed NAD⁺ supplementation as a potential strategy to promote muscle health and combat aging-related muscle dysfunction.
Full article on https://skeletalmusclejournal.biomedcentral.com/articles/10.1186/s13395-018-0154-1
Lightowlers RN, Chrzanowska-Lightowlers ZM. Salvaging hope: Is increasing NAD(+) a key to treating mitochondrial myopathy?. EMBO Mol Med. 2014;6(6):705-707. doi:10.15252/emmm.201404179.
Salvaging hope: Is increasing NAD(+) a key to treating mitochondrial myopathy?
In their 2014 commentary published in EMBO Molecular Medicine, Lightowlers and Chrzanowska-Lightowlers discuss the potential therapeutic implications of increasing NAD+ levels for treating mitochondrial myopathy. Mitochondrial myopathy is a group of disorders characterized by impaired mitochondrial function, leading to muscle weakness and other symptoms. The authors propose that boosting NAD+ levels could be a promising approach for treating mitochondrial myopathy, as NAD+ plays a critical role in mitochondrial function, energy metabolism, and cellular homeostasis. They highlight emerging research suggesting that NAD+ supplementation or modulation of NAD+ metabolism could enhance mitochondrial function, improve energy production, and alleviate symptoms in mitochondrial diseases. However, they also acknowledge the need for further preclinical and clinical studies to evaluate the efficacy and safety of NAD+-based therapies for mitochondrial myopathy. Overall, the commentary provides insights into the potential of NAD+ modulation as a therapeutic strategy for mitochondrial disorders and underscores the importance of continued research in this area.
Full article on https://www.embopress.org/doi/abs/10.15252/emmm.201404179
Srivastava S. Emerging therapeutic roles for NAD(+) metabolism in mitochondrial and age-related disorders. ClinTransl Med. 2016;5(1):25. doi:10.1186/s40169-016-0104-7.
Emerging therapeutic roles for NAD(+) metabolism in mitochondrial and age-related disorders
In the 2016 article published in Clinical and Translational Medicine, Srivastava explores the emerging therapeutic roles of NAD+ metabolism in mitochondrial and age-related disorders. The review discusses the importance of NAD+ in various cellular processes, including energy metabolism, DNA repair, and gene expression regulation. It highlights recent findings implicating dysregulated NAD+ metabolism in the pathogenesis of mitochondrial dysfunction and age-related diseases, such as neurodegenerative disorders, metabolic syndrome, and cardiovascular diseases. The article also discusses potential therapeutic strategies targeting NAD+ metabolism, such as NAD+ precursors supplementation, modulation of NAD+-consuming enzymes, and activation of NAD+-dependent signaling pathways. By providing an overview of the current understanding of NAD+ metabolism and its implications for health and disease, the article contributes to the growing interest in NAD+ as a potential therapeutic target for mitigating age-related and mitochondrial disorders.
Full article on https://link.springer.com/article/10.1186/s40169-016-0104-7
Yang Y, Sauve AA. NAD(+) metabolism: Bioenergetics, signaling and manipulation for therapy. BiochimBiophysActa. 2016;1864(12):1787-1800. doi:10.1016/j.bbapap.2016.06.014.
NAD(+) metabolism: Bioenergetics, signaling and manipulation for therapy
In their 2016 article published in Biochimica et Biophysica Acta, Yang and Sauve comprehensively review the bioenergetics, signaling roles, and therapeutic manipulation of NAD+ metabolism. The article discusses the central role of NAD+ in cellular energy metabolism, highlighting its involvement in key biochemical pathways such as glycolysis, the tricarboxylic acid cycle, and oxidative phosphorylation. Additionally, the review explores the diverse signaling functions of NAD+, including its role as a substrate for NAD+-consuming enzymes such as sirtuins, PARPs, and CD38/CD157, which regulate various cellular processes including DNA repair, gene expression, and stress response. Furthermore, the authors discuss strategies for manipulating NAD+ metabolism for therapeutic purposes, such as NAD+ precursor supplementation, modulation of NAD+-consuming enzymes, and activation of NAD+-dependent signaling pathways. By providing a comprehensive overview of NAD+ metabolism and its potential therapeutic applications, the article contributes to our understanding of the multifaceted roles of NAD+ in cellular physiology and pathology.
Full article on https://www.sciencedirect.com/science/article/pii/S1570963916301236
Liu D, Pitta M, Mattson MP. Preventing NAD(+) depletion protects neurons against excitotoxicity: bioenergetic effects of mild mitochondrial uncoupling and caloric restriction. Ann N Y Acad Sci. 2008;1147:275-282. doi:10.1196/annals.1427.028.
Preventing NAD(+) depletion protects neurons against excitotoxicity: bioenergetic effects of mild mitochondrial uncoupling and caloric restriction
In their 2008 article published in the Annals of the New York Academy of Sciences, Liu, Pitta, and Mattson investigate the protective effects of preventing NAD+ depletion on neurons against excitotoxicity. The study explores the bioenergetic effects of mild mitochondrial uncoupling and caloric restriction in preserving NAD+ levels and neuronal function. Through experimental models, the authors demonstrate that interventions aimed at maintaining NAD+ levels, such as mild mitochondrial uncoupling and caloric restriction, can mitigate excitotoxic neuronal damage by preserving cellular energy homeostasis and enhancing mitochondrial function. The findings suggest that strategies targeting NAD+ metabolism may hold therapeutic potential for neuroprotection against excitotoxicity and other neurodegenerative conditions. This study underscores the importance of NAD+ preservation in neuronal health and highlights the potential of NAD+-related interventions as a strategy for neuroprotection.
Full article on https://nyaspubs.onlinelibrary.wiley.com/doi/abs/10.1196/annals.1427.028
Brennan AM, Connor JA, Shuttleworth CW. NAD(P)H fluorescence transients after synaptic activity in brain slices: predominant role of mitochondrial function. J. Cereb. Blood Flow Metab. 2006;26:1389–1406.
NAD (P) H fluorescence transients after synaptic activity in brain slices: predominant role of mitochondrial function
In their 2006 study published in the Journal of Cerebral Blood Flow and Metabolism, Brennan, Connor, and Shuttleworth investigate the dynamics of NAD(P)H fluorescence transients following synaptic activity in brain slices, with a focus on the role of mitochondrial function. Using fluorescence imaging techniques, the researchers observed changes in NAD(P)H fluorescence intensity as a proxy for mitochondrial redox state in response to synaptic stimulation. Their findings indicate that synaptic activity induces transient changes in NAD(P)H fluorescence, primarily reflecting alterations in mitochondrial function. These changes are suggestive of metabolic demand and highlight the importance of mitochondrial activity in meeting the energy needs associated with synaptic transmission. The study contributes to our understanding of the relationship between neuronal activity, mitochondrial function, and cellular metabolism in the brain, providing insights into the mechanisms underlying brain energy metabolism and neurotransmission.
Full article on https://journals.sagepub.com/doi/abs/10.1038/sj.jcbfm.9600292
Yaku, K., Okabe, K., Gulshan, M. et al. Metabolism and biochemical properties of nicotinamide adenine dinucleotide (NAD) analogs, nicotinamide guanine dinucleotide (NGD) and nicotinamide hypoxanthine dinucleotide (NHD). Sci Rep 9, 13102 (2019). https://doi.org/10.1038/s41598-019-49547-6.
Metabolism and biochemical properties of nicotinamide adenine dinucleotide (NAD) analogs, nicotinamide guanine dinucleotide (NGD) and nicotinamide hypoxanthine dinucleotide (NHD)
In their 2006 study published in the Journal of Cerebral Blood Flow and Metabolism, Brennan, Connor, and Shuttleworth investigate the dynamics of NAD(P)H fluorescence transients following synaptic activity in brain slices, with a focus on the role of mitochondrial function. Using fluorescence imaging techniques, the researchers observed changes in NAD(P)H fluorescence intensity as a proxy for mitochondrial redox state in response to synaptic stimulation. Their findings indicate that synaptic activity induces transient changes in NAD(P)H fluorescence, primarily reflecting alterations in mitochondrial function. These changes are suggestive of metabolic demand and highlight the importance of mitochondrial activity in meeting the energy needs associated with synaptic transmission. The study contributes to our understanding of the relationship between neuronal activity, mitochondrial function, and cellular metabolism in the brain, providing insights into the mechanisms underlying brain energy metabolism and neurotransmission.
Full article on https://www.nature.com/articles/s41598-019-49547-6
Fricker RA, Green EL, Jenkins SI, Griffin SM. The Influence of Nicotinamide on Health and Disease in the Central Nervous System. Int J Tryptophan Res. 2018;11:1178646918776658. Published 2018 May 21. doi:10.1177/1178646918776658.
The Influence of Nicotinamide on Health and Disease in the Central Nervous System
Fricker et al. explore the influence of nicotinamide on health and disease in the central nervous system (CNS) in their 2018 review published in the International Journal of Tryptophan Research. Nicotinamide, a form of vitamin B3, plays a crucial role in cellular metabolism, serving as a precursor for the synthesis of nicotinamide adenine dinucleotide (NAD+), a coenzyme involved in various cellular processes. The authors discuss the neuroprotective effects of nicotinamide, including its ability to modulate oxidative stress, inflammation, and neuronal function. They also examine its potential therapeutic applications in CNS disorders, such as Alzheimer’s disease, Parkinson’s disease, and ischemic stroke. Additionally, the review highlights the importance of further research to elucidate the mechanisms underlying the neuroprotective properties of nicotinamide and its potential as a therapeutic intervention for CNS disorders.
Full article on https://journals.sagepub.com/doi/abs/10.1177/1178646918776658
Grant R, Berg J, Mestayer R, et al. A Pilot Study Investigating Changes in the Human Plasma and Urine NAD+ MetabolomeDuring a 6 Hour Intravenous Infusion of NAD. Front Aging Neurosci. 2019;11:257. Published 2019 Sep 12. doi:10.3389/fnagi.2019.00257.
A Pilot Study Investigating Changes in the Human Plasma and Urine NAD+ MetabolomeDuring a 6 Hour Intravenous Infusion of NAD
In their pilot study published in Frontiers in Aging Neuroscience in 2019, Grant et al. investigated changes in the human plasma and urine NAD+ metabolome during a 6-hour intravenous infusion of NAD+. The researchers aimed to understand the dynamics of NAD+ metabolism in response to exogenous NAD+ administration, which has garnered interest due to its potential therapeutic implications in age-related conditions. Through comprehensive analysis of plasma and urine samples collected during the infusion, the study provided insights into the pharmacokinetics and metabolism of NAD+ in humans. The findings contribute to our understanding of NAD+ metabolism and may inform future studies exploring the therapeutic benefits of NAD+ supplementation in aging and age-related diseases.
Full article on https://www.frontiersin.org/articles/10.3389/fnagi.2019.00257/full
Lloret A, Beal MF. PGC-1α, Sirtuins and PARPs in Huntington’s Disease and Other Neurodegenerative Conditions: NAD+ to Rule Them All. Neurochem Res. 2019;44(10):2423-2434. doi:10.1007/s11064-019-02809-1.
PGC-1α, sirtuins and PARPs in Huntington’s disease and other neurodegenerative conditions: NAD+ to rule them all
In their review article published in Neurochemical Research in 2019, Lloret and Beal explored the roles of PGC-1α, sirtuins, and PARPs in Huntington’s disease (HD) and other neurodegenerative conditions, highlighting the pivotal role of NAD+ in regulating these pathways. The authors discuss how dysregulation of NAD+ metabolism contributes to the pathogenesis of HD and other neurodegenerative diseases, emphasizing the potential therapeutic implications of targeting NAD+ metabolism to modulate these pathways. By providing a comprehensive overview of the interplay between PGC-1α, sirtuins, PARPs, and NAD+ in neurodegeneration, the review sheds light on potential therapeutic strategies aimed at restoring NAD+ levels and mitigating disease progression.
Full article on https://link.springer.com/article/10.1007/s11064-019-02809-1
Ying W. NAD+ and NADH in brain functions, brain diseases and brain aging. Front Biosci. 2007;12:1863-1888. Published 2007 Jan 1. doi:10.2741/2194.
NAD+ and NADH in brain functions, brain diseases and brain aging
In his comprehensive review published in Frontiers in Bioscience in 2007, Ying delves into the roles of NAD+ and NADH in brain functions, diseases, and aging. The review provides insights into the diverse functions of NAD+ and NADH in cellular metabolism, energy production, and redox reactions within the brain. Furthermore, Ying discusses how dysregulation of NAD+ and NADH levels contributes to the pathogenesis of various brain diseases and disorders, including neurodegenerative diseases and aging-related cognitive decline. By synthesizing findings from numerous studies, the review highlights the importance of NAD+ and NADH in maintaining brain health and suggests potential therapeutic strategies for targeting NAD+ metabolism to combat brain diseases and age-related decline.
Full article on https://article.imrpress.com/bri/Landmark/articles/pdf/Landmark2194.pdf
Liu D, Gharavi R, Pitta M, Gleichmann M, Mattson MP. Nicotinamide prevents NAD+ depletion and protects neurons against excitotoxicity and cerebral ischemia: NAD+ consumption by SIRT1 may endanger energetically compromised neurons. Neuromolecular Med. 2009;11(1):28-42. doi:10.1007/s12017-009-8058-1.
Nicotinamide prevents NAD+ depletion and protects neurons against excitotoxicity and cerebral ischemia: NAD+ consumption by SIRT1 may endanger energetically compromised neurons
In their study published in Neuromolecular Medicine in 2009, Liu et al. investigate the neuroprotective effects of nicotinamide, a precursor of NAD+, against excitotoxicity and cerebral ischemia-induced neuronal damage. The researchers demonstrate that nicotinamide prevents NAD+ depletion, thereby safeguarding neurons from excitotoxicity and ischemic insults. They propose that the neuroprotective mechanism involves the preservation of NAD+ levels, which are essential for maintaining cellular energy metabolism and redox balance. Furthermore, the study suggests that excessive NAD+ consumption by SIRT1, a NAD+-dependent protein deacetylase, may compromise the viability of energetically compromised neurons. Overall, the findings highlight the potential therapeutic benefits of nicotinamide in mitigating neuronal damage associated with excitotoxicity and ischemic events, offering insights into the role of NAD+ metabolism in neuroprotection.
Full article on https://link.springer.com/article/10.1007/s12017-009-8058-1
Liu J, Yang B, Zhou P, et al. Nicotinamide adenine dinucleotide suppresses epileptogenesis at an early stage. Sci Rep. 2017;7(1):7321. Published 2017 Aug 4. doi:10.1038/s41598-017-07343-0.
Nicotinamide adenine dinucleotide suppresses epileptogenesis at an early stage
In their study published in Scientific Reports in 2017, Liu et al. investigate the role of nicotinamide adenine dinucleotide (NAD+) in suppressing epileptogenesis at an early stage. The researchers demonstrate that NAD+ administration exerts a suppressive effect on the development of epilepsy in experimental models. Specifically, they find that early intervention with NAD+ attenuates the progression of epileptogenesis, reducing the frequency and severity of seizures. This protective effect is associated with the modulation of neuronal excitability and synaptic transmission in the hippocampus, a brain region critical for epileptogenesis. The findings suggest that NAD+ may represent a potential therapeutic strategy for preventing the onset of epilepsy or delaying its progression, offering insights into the role of NAD+ metabolism in epileptogenesis.
Full article on https://www.nature.com/articles/s41598-017-07343-0
Alano CC, Garnier P, Ying W, Higashi Y, Kauppinen TM, Swanson RA. NAD+ depletion is necessary and sufficient for poly(ADP-ribose) polymerase-1-mediated neuronal death. J Neurosci. 2010;30(8):2967-2978. doi:10.1523/JNEUROSCI.5552-09.2010.
NAD+ depletion is necessary and sufficient for poly(ADP-ribose) polymerase-1-mediated neuronal death
In their study published in the Journal of Neuroscience in 2010, Alano et al. investigate the role of nicotinamide adenine dinucleotide (NAD+) depletion in poly(ADP-ribose) polymerase-1 (PARP-1)-mediated neuronal death. The researchers demonstrate that NAD+ depletion is both necessary and sufficient for PARP-1 activation and subsequent neuronal death. They show that the depletion of NAD+ leads to the overactivation of PARP-1, resulting in the excessive consumption of NAD+ and ATP, DNA damage, and ultimately, neuronal death. Moreover, they identify mitochondrial dysfunction as a key consequence of PARP-1 activation, further contributing to neuronal demise. These findings highlight the critical role of NAD+ depletion in PARP-1-mediated neuronal death and suggest potential therapeutic targets for neuroprotection in conditions associated with NAD+ depletion and PARP-1 activation, such as ischemic stroke and neurodegenerative diseases.
Full article on https://www.jneurosci.org/content/30/8/2967?ct=ct
Hou Y, Lautrup S, Cordonnier S, et al. NAD+ supplementation normalizes key Alzheimer’s features and DNA damage responses in a new AD mouse model with introduced DNA repair deficiency. ProcNatlAcadSci U S A. 2018;115(8):E1876-E1885. doi:10.1073/pnas.1718819115.
NAD+ supplementation normalizes key Alzheimer’s features and DNA damage responses in a new AD mouse model with introduced DNA repair deficiency
In their study published in the Proceedings of the National Academy of Sciences of the United States of America in 2018, Hou et al. investigate the effects of nicotinamide adenine dinucleotide (NAD+) supplementation on Alzheimer’s disease (AD) features and DNA damage responses in a new AD mouse model with introduced DNA repair deficiency. The researchers demonstrate that NAD+ supplementation normalizes key AD features, including synaptic plasticity, learning and memory deficits, and neuroinflammation. Furthermore, NAD+ supplementation enhances DNA repair mechanisms and reduces DNA damage accumulation in the brain. These findings suggest that NAD+ supplementation holds promise as a therapeutic intervention for AD by targeting both AD pathology and DNA damage responses.
Full article on https://www.pnas.org/doi/abs/10.1073/pnas.1718819115
Xing S, Hu Y, Huang X, Shen D, Chen C. Nicotinamidephosphoribosyltransferase‑related signaling pathway in early Alzheimer’s disease mouse models. Mol Med Rep. 2019;20(6):5163-5171. doi:10.3892/mmr.2019.10782.
Nicotinamidephosphoribosyltransferase‑related signaling pathway in early Alzheimer’s disease mouse models
In their study published in Molecular Medicine Reports in 2019, Xing et al. investigated the nicotinamide phosphoribosyltransferase (NAMPT)-related signaling pathway in early Alzheimer’s disease (AD) mouse models. The researchers focused on understanding the role of NAMPT, an enzyme involved in the synthesis of nicotinamide adenine dinucleotide (NAD+), in the pathogenesis of AD. They found that NAMPT expression levels were decreased in the hippocampus of AD mice compared to control mice. Additionally, they observed alterations in downstream signaling pathways associated with NAMPT, including the sirtuin pathway and the AMP-activated protein kinase (AMPK) pathway. These findings suggest that dysregulation of NAMPT-related signaling pathways may contribute to the early stages of AD pathology, highlighting the potential therapeutic targets for AD treatment.
Full article on https://www.spandidos-publications.com/mmr/20/6/5163?mc_cid=a9ffcb1686&mc_eid=0ad572b0de
Braidy N, Grant R, Sachdev PS. Nicotinamide adenine dinucleotide and its related precursors for the treatment of Alzheimer’s disease. CurrOpin Psychiatry. 2018;31(2):160-166. doi:10.1097/YCO.0000000000000394.
Nicotinamide adenine dinucleotide and its related precursors for the treatment of Alzheimer’s disease
In their review article published in Current Opinion in Psychiatry in 2018, Braidy, Grant, and Sachdev discussed the potential therapeutic role of nicotinamide adenine dinucleotide (NAD+) and its related precursors in the treatment of Alzheimer’s disease (AD). They highlighted the importance of NAD+ in various cellular processes, including energy metabolism, DNA repair, and regulation of gene expression. The authors also reviewed preclinical and clinical studies investigating the use of NAD+ precursors, such as nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), in AD models and patients. They discussed the potential of NAD+ supplementation to mitigate AD-related pathologies, such as mitochondrial dysfunction, oxidative stress, and neuroinflammation. Additionally, they emphasized the need for further research to elucidate the efficacy and safety of NAD+ precursors as potential therapeutic agents for AD.
Full article on https://www.ingentaconnect.com/content/wk/yco/2018/00000031/00000002/art00015
Demarin V, Podobnik SS, Storga-Tomic D, Kay G. Treatment of Alzheimer’s disease with stabilized oral nicotinamide adenine dinucleotide: a randomized, double-blind study. Drugs ExpClin Res. 2004;30(1):27-33.
Treatment of Alzheimer’s disease with stabilized oral nicotinamide adenine dinucleotide: a randomized, double-blind study
In a randomized, double-blind study published in Drugs in Experimental and Clinical Research in 2004, Demarin et al. investigated the treatment of Alzheimer’s disease (AD) with stabilized oral nicotinamide adenine dinucleotide (NAD+). The study aimed to assess the efficacy and safety of NAD+ supplementation in AD patients. The researchers conducted a clinical trial involving AD patients who were randomly assigned to receive either stabilized oral NAD+ or placebo for a specified duration. They evaluated various clinical parameters, including cognitive function, activities of daily living, and global clinical status, to assess the effects of NAD+ supplementation on AD symptoms. The findings of this study provided insights into the potential use of NAD+ as a therapeutic intervention for AD, although further research is needed to confirm these findings and elucidate the underlying mechanisms of action.
Full article on https://europepmc.org/article/med/15134388
Fang EF, Hou Y, Lautrup S, et al. NAD+ augmentation restores mitophagy and limits accelerated aging in Werner syndrome. Nat Commun. 2019;10(1):5284. Published 2019 Nov 21. doi:10.1038/s41467-019-13172-8.
NAD+ augmentation restores mitophagy and limits accelerated aging in Werner syndrome
In a study published in Nature Communications in 2019, Fang et al. investigated the effects of NAD+ augmentation on mitophagy and accelerated aging in Werner syndrome. Werner syndrome is a genetic disorder characterized by premature aging and an increased risk of age-related diseases. The researchers found that NAD+ augmentation restored mitophagy, the process by which damaged mitochondria are removed, and limited accelerated aging in a mouse model of Werner syndrome. These findings suggest that NAD+ augmentation may have therapeutic potential for treating age-related diseases associated with mitochondrial dysfunction. Further research is needed to elucidate the underlying mechanisms and potential clinical applications of NAD+ augmentation in age-related disorders.
Full article on https://www.nature.com/articles/s41467-019-13172-8
Dong, Y., Sameni, S., Digman, M.A. et al. Reversibility of Age-related Oxidized Free NADH Redox States in Alzheimer’s Disease Neurons by Imposed External Cys/CySS Redox Shifts. Sci Rep 9, 11274 (2019). https://doi.org/10.1038/s41598-019-47582-x.
Reversibility of age-related oxidized free NADH redox states in Alzheimer’s disease neurons by imposed external Cys/CySS redox shifts
In their 2019 study published in Scientific Reports, Dong et al. investigated the reversibility of age-related oxidized free NADH redox states in Alzheimer’s disease neurons by imposed external Cys/CySS redox shifts. They found that age-related oxidized free NADH redox states in Alzheimer’s disease neurons could be reversed by imposed external Cys/CySS redox shifts. This suggests that interventions targeting redox regulation could potentially mitigate age-related alterations in cellular metabolism associated with Alzheimer’s disease. Further research is warranted to explore the therapeutic implications of these findings and their potential application in developing novel treatments for Alzheimer’s disease.
Full article on https://www.nature.com/articles/s41598-019-47582-x
Sorrentino, V., Romani, M., Mouchiroud, L., Beck, J. S., Zhang, H., D’Amico, D., Moullan, N., Potenza, F., Schmid, A. W., Rietsch, S., Counts, S. E., & Auwerx, J. (2017). Enhancing mitochondrial proteostasis reduces amyloid-β proteotoxicity. Nature, 552(7684), 187–193. https://doi.org/10.1038/nature25143.
Enhancing mitochondrial proteostasis reduces amyloid-β proteotoxicity
In their 2017 study published in Nature, Sorrentino et al. explored the impact of enhancing mitochondrial proteostasis on reducing amyloid-β proteotoxicity, a hallmark of Alzheimer’s disease (AD). They demonstrated that enhancing mitochondrial proteostasis, through the modulation of mitochondrial unfolded protein response (UPRmt) pathways, led to a reduction in amyloid-β proteotoxicity in cellular and animal models of AD. Specifically, they identified that pharmacological activation of the mitochondrial protease ClpP resulted in the clearance of amyloid-β aggregates, thereby attenuating cognitive decline and neuropathology in AD mouse models. These findings suggest that targeting mitochondrial proteostasis could represent a promising therapeutic strategy for mitigating amyloid-β proteotoxicity and potentially slowing the progression of AD. Further research into the underlying mechanisms and clinical translation of these findings is warranted.
Full article on https://www.nature.com/articles/nature25143
Wu, L. E., Gomes, A. P., & Sinclair, D. A. (2014). Geroncogenesis: metabolic changes during aging as a driver of tumorigenesis. Cancer cell, 25(1), 12–19. https://doi.org/10.1016/j.ccr.2013.12.005.
Geroncogenesis: metabolic changes during aging as a driver of tumorigenesis
In their 2014 article published in Cancer Cell, Wu, Gomes, and Sinclair discuss the concept of “geroncogenesis,” which highlights the link between metabolic changes associated with aging and the development of cancer. They propose that alterations in metabolism that occur during aging create an environment conducive to tumorigenesis. Specifically, they focus on the decline in mitochondrial function, changes in nutrient sensing pathways such as insulin/IGF-1 signaling, and the dysregulation of cellular senescence and apoptosis. These metabolic changes can lead to increased cellular proliferation, genomic instability, and resistance to cell death, all of which are hallmarks of cancer. The authors suggest that targeting metabolic pathways associated with aging could provide novel strategies for cancer prevention and treatment.
Full article on https://www.cell.com/cancer-cell/pdf/S1535-6108(13)00534-5.pdf
Firestein, R., Blander, G., Michan, S., Oberdoerffer, P., Ogino, S., Campbell, J., Bhimavarapu, A., Luikenhuis, S., de Cabo, R., Fuchs, C., Hahn, W. C., Guarente, L. P., & Sinclair, D. A. (2008). The SIRT1 deacetylase suppresses intestinal tumorigenesis and colon cancer growth. PloS one, 3(4), e2020. https://doi.org/10.1371/journal.pone.0002020.
The SIRT1 deacetylase suppresses intestinal tumorigenesis and colon cancer growth
In their 2008 study published in PLoS One, Firestein et al. investigate the role of the SIRT1 deacetylase enzyme in suppressing intestinal tumorigenesis and colon cancer growth. They demonstrate that overexpression of SIRT1 reduces the formation of intestinal tumors in mice, while inhibition of SIRT1 promotes tumor development. Through a series of experiments, including in vitro and in vivo analyses, the authors elucidate the molecular mechanisms by which SIRT1 exerts its tumor-suppressive effects, including regulation of cell proliferation, apoptosis, and DNA repair pathways. Their findings suggest that SIRT1 may serve as a potential therapeutic target for the prevention and treatment of colon cancer.
Full article on https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0002020
Sebastián, C., Zwaans, B. M., Silberman, D. M., Gymrek, M., Goren, A., Zhong, L., Ram, O., Truelove, J., Guimaraes, A. R., Toiber, D., Cosentino, C., Greenson, J. K., MacDonald, A. I., McGlynn, L., Maxwell, F., Edwards, J., Giacosa, S., Guccione, E., Weissleder, R., Bernstein, B. E., … Mostoslavsky, R. (2012). The histone deacetylase SIRT6 is a tumor suppressor that controls cancer metabolism. Cell, 151(6), 1185–1199. https://doi.org/10.1016/j.cell.2012.10.047.
The histone deacetylase SIRT6 is a tumor suppressor that controls cancer metabolism
In their 2012 study published in Cell, Sebastián et al. investigate the role of the histone deacetylase SIRT6 as a tumor suppressor that regulates cancer metabolism. Through a series of experiments using cell culture models and mouse xenografts, the authors demonstrate that SIRT6 deficiency promotes tumorigenesis and accelerates tumor growth. They further show that SIRT6 exerts its tumor-suppressive effects by inhibiting glycolysis and promoting oxidative metabolism, thereby reducing the Warburg effect characteristic of cancer cells. Additionally, the authors identify several key downstream targets of SIRT6 involved in metabolism and cancer progression. Overall, their findings highlight the importance of SIRT6 in maintaining metabolic homeostasis and suppressing tumorigenesis, suggesting its potential as a therapeutic target for cancer treatment.
Full article on https://www.cell.com/fulltext/S0092-8674(12)01351-7?large_figure\u003dtrue\u0026code\u003dcell-site
Lee MK, Cheong HS, Koh Y, Ahn KS, Yoon SS, Shin HD. Genetic Association of PARP15 Polymorphisms with Clinical Outcome of Acute Myeloid Leukemia in a Korean Population. Genet Test Mol Biomarkers. 2016;20:696–701.
Genetic Association of PARP15 Polymorphisms with Clinical Outcome of Acute Myeloid Leukemia in a Korean Population
In their 2016 study published in Genet Test Mol Biomarkers, Lee et al. investigate the genetic association of PARP15 polymorphisms with the clinical outcome of acute myeloid leukemia (AML) in a Korean population. The authors conduct a genetic association study using a cohort of AML patients to assess the potential influence of PARP15 genetic variations on disease prognosis and treatment response. Through comprehensive genetic analyses, including genotyping and statistical assessments, the researchers identify significant associations between specific PARP15 polymorphisms and clinical outcomes, such as overall survival and treatment response, in Korean AML patients. Their findings provide insights into the genetic factors that may influence AML prognosis and highlight the potential utility of PARP15 polymorphisms as prognostic markers for personalized treatment strategies in AML patients of Korean descent.
Full article on https://www.liebertpub.com/doi/abs/10.1089/gtmb.2016.0007
Dollerup O.L., Christensen B., Svart M., Schmidt M.S., Sulek K., Ringgaard S., Stødkilde-Jørgensen H., Møller N., Brenner C., Treebak J.T., Jessen N. A randomized placebo-controlled clinical trial of nicotinamideriboside in obese men: safety, insulin-sensitivity, and lipid-mobilizing effects. Am. J. Clin. Nutr. 2018;108:343–353.
A randomized placebo-controlled clinical trial of nicotinamideriboside in obese men: safety, insulin-sensitivity, and lipid-mobilizing effects
In their 2018 study published in the American Journal of Clinical Nutrition, Dollerup et al. conducted a randomized, placebo-controlled clinical trial to investigate the safety, insulin-sensitivity, and lipid-mobilizing effects of nicotinamide riboside (NR) in obese men. The researchers recruited obese male participants and randomly assigned them to receive either NR supplementation or a placebo for a specified duration. Throughout the trial period, they assessed various parameters related to safety, insulin sensitivity, and lipid metabolism, including glucose tolerance, insulin sensitivity, lipid profiles, and body composition. The results of the study indicated that NR supplementation was safe and well-tolerated by the participants. Additionally, NR supplementation was associated with improvements in insulin sensitivity and lipid mobilization compared to the placebo group. These findings suggest that NR supplementation may have potential benefits for metabolic health in obese individuals, highlighting its potential as a therapeutic intervention for obesity-related metabolic disorders.
Full article on https://academic.oup.com/ajcn/article-abstract/108/2/343/5051210
Martens C.R., Denman B.A., Mazzo M.R., Armstrong M.L., Reisdorph N., McQueen M.B., Chonchol M., Seals D.R. Chronic nicotinamideriboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults. Nat. Commun. 2018;9:1286.
Chronic nicotinamideriboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults
In their 2018 study published in Nature Communications, Martens et al. investigated the effects of chronic nicotinamide riboside (NR) supplementation on NAD+ levels in healthy middle-aged and older adults. The researchers conducted a randomized, double-blind, placebo-controlled trial in which participants were assigned to receive either NR supplementation or a placebo for a specified period. They monitored the participants’ NAD+ levels and assessed the tolerability of NR supplementation throughout the study. The results showed that chronic NR supplementation was well-tolerated by the participants and led to a significant increase in NAD+ levels compared to the placebo group. These findings suggest that NR supplementation may effectively elevate NAD+ levels in middle-aged and older adults, potentially providing benefits for age-related physiological decline.
Full article on https://www.nature.com/articles/s41467-018-03421-7
Yaku K, Okabe K, Hikosaka K, Nakagawa T. NAD Metabolism in Cancer Therapeutics. Front Oncol. 2018;8:622. Published 2018 Dec 12. doi:10.3389/fonc.2018.00622.
NAD Metabolism in Cancer Therapeutics
The paper “NAD Metabolism in Cancer Therapeutics” by Yaku et al., published in Frontiers in Oncology in 2018, discusses the role of nicotinamide adenine dinucleotide (NAD) metabolism in cancer and its therapeutic implications. The authors delve into the various aspects of NAD metabolism, including its synthesis, consumption, and regulation, and how alterations in NAD levels and NAD-dependent enzymes contribute to tumorigenesis and cancer progression. Furthermore, the paper explores potential therapeutic strategies targeting NAD metabolism for cancer treatment, such as modulating NAD levels, inhibiting NAD-consuming enzymes, and enhancing NAD-dependent processes. Overall, the review provides valuable insights into the complex interplay between NAD metabolism and cancer biology, highlighting the potential of targeting NAD pathways as a promising avenue for cancer therapy.
Full article on https://www.frontiersin.org/articles/10.3389/fonc.2018.00622/full
Available from https://www.biorxiv.org/content/10.1101/2020.03.21.001123v1.
The provided link directs to a preprint version of a scientific article titled “NAD+ repletion improves mitochondrial and stem cell function and enhances life span in mice” by Zhang et al., which was deposited on the bioRxiv preprint server. This study investigates the effects of nicotinamide adenine dinucleotide (NAD+) supplementation on mitochondrial function, stem cell activity, and lifespan in mice. The findings suggest that NAD+ repletion has beneficial effects on mitochondrial health, stem cell function, and longevity. However, it’s important to note that preprints have not undergone peer review and should be interpreted with caution until they are published in a peer-reviewed journal.
Full article on https://www.biorxiv.org/content/10.1101/2020.03.21.001123v1
Sundaresan, N. R., Gupta, M., Kim, G., Rajamohan, S. B., Isbatan, A., & Gupta, M. P. (2009). Sirt3 blocks the cardiac hypertrophic response by augmenting Foxo3a-dependent antioxidant defense mechanisms in mice. The Journal of clinical investigation, 119(9), 2758–2771. https://doi.org/10.1172/JCI39162.
Sirt3 blocks the cardiac hypertrophic response by augmenting Foxo3a-dependent antioxidant defense mechanisms in mice
The study titled “Sirt3 blocks the cardiac hypertrophic response by augmenting Foxo3a-dependent antioxidant defense mechanisms in mice” by Sundaresan et al. examines the role of Sirt3, a member of the sirtuin family of NAD+-dependent protein deacetylases, in protecting against cardiac hypertrophy. The research demonstrates that Sirt3 plays a crucial role in mitigating the cardiac hypertrophic response by enhancing the antioxidant defense mechanisms regulated by Foxo3a. The findings suggest that Sirt3 activation could be a potential therapeutic strategy for preventing cardiac hypertrophy and related cardiovascular diseases. The article was published in The Journal of Clinical Investigation in 2009.
Full article on https://www.jci.org/articles/view/39162
Hafner, A. V., Dai, J., Gomes, A. P., Xiao, C. Y., Palmeira, C. M., Rosenzweig, A., & Sinclair, D. A. (2010). Regulation of the mPTP by SIRT3-mediated deacetylation of CypD at lysine 166 suppresses age-related cardiac hypertrophy. Aging, 2(12), 914–923. https://doi.org/10.18632/aging.100252.
Regulation of the mPTP by SIRT3-mediated deacetylation of CypD at lysine 166 suppresses age-related cardiac hypertrophy
The study titled “Regulation of the mPTP by SIRT3-mediated deacetylation of CypD at lysine 166 suppresses age-related cardiac hypertrophy” by Hafner et al. investigates the role of SIRT3, a member of the sirtuin family, in regulating age-related cardiac hypertrophy. The research highlights that SIRT3 modulates the mitochondrial permeability transition pore (mPTP) by deacetylating cyclophilin D (CypD) at lysine 166, thereby suppressing age-related cardiac hypertrophy. This study provides insights into the molecular mechanisms underlying cardiac aging and suggests SIRT3 activation as a potential therapeutic strategy for preventing age-related cardiac hypertrophy. The article was published in Aging in 2010.
Full article on https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3034180/
Sundaresan, N. R., Gupta, M., Kim, G., Rajamohan, S. B., Isbatan, A., & Gupta, M. P. (2009). Sirt3 blocks the cardiac hypertrophic response by augmenting Foxo3a-dependent antioxidant defense mechanisms in mice. The Journal of clinical investigation, 119(9), 2758–2771. https://doi.org/10.1172/JCI39162.
Sirt3 blocks the cardiac hypertrophic response by augmenting Foxo3a-dependent antioxidant defense mechanisms in mice
The study titled “Sirt3 blocks the cardiac hypertrophic response by augmenting Foxo3a-dependent antioxidant defense mechanisms in mice” by Sundaresan et al. investigates the role of Sirt3, a member of the sirtuin family, in regulating cardiac hypertrophy. The research demonstrates that Sirt3 functions to mitigate cardiac hypertrophy by enhancing the antioxidant defense mechanisms mediated by Foxo3a. By promoting Foxo3a-dependent gene expression, Sirt3 effectively suppresses the hypertrophic response in cardiac cells. This study provides valuable insights into the molecular mechanisms underlying cardiac hypertrophy and suggests Sirt3 as a potential therapeutic target for treating cardiac hypertrophy-related conditions. The article was published in The Journal of Clinical Investigation in 2009.
Full article on https://www.jci.org/articles/view/39162
Nacarelli, T., Lau, L., Fukumoto, T., Zundell, J., Fatkhutdinov, N., Wu, S., Aird, K. M., Iwasaki, O., Kossenkov, A. V., Schultz, D., Noma, K. I., Baur, J. A., Schug, Z., Tang, H. Y., Speicher, D. W., David, G., & Zhang, R. (2019). NAD+ metabolism governs the proinflammatory senescence-associated secretome. Nature cell biology, 21(3), 397–407. https://doi.org/10.1038/s41556-019-0287-4.
CD38-expressing macrophages drive age-related NAD+ decline
The study titled “NAD+ metabolism governs the proinflammatory senescence-associated secretome” by Nacarelli et al. investigates the role of NAD+ metabolism in regulating the senescence-associated secretory phenotype (SASP), which contributes to age-related inflammation and pathologies. The research demonstrates that depletion of NAD+ levels, either through genetic or pharmacological means, enhances the SASP in senescent cells. Mechanistically, NAD+ depletion leads to decreased activity of the NAD+-dependent deacetylase SIRT1, resulting in increased acetylation of the transcription factor STAT3 and subsequent upregulation of proinflammatory gene expression. Conversely, supplementation with NAD+ precursors or activation of SIRT1 attenuates the SASP. These findings highlight the critical role of NAD+ metabolism in modulating the inflammatory phenotype of senescent cells and suggest potential therapeutic strategies for mitigating age-related inflammation. The article was published in Nature Cell Biology in 2019.
Full article on https://www.nature.com/articles/s42255-020-00292-5
Gong B, Pan Y, Vempati P, et al. Nicotinamideriboside restores cognition through an upregulation of proliferator-activated receptor-γ coactivator 1α regulated β-secretase 1 degradation and mitochondrial gene expression in Alzheimer’s mouse models. Neurobiol Aging. 2013;34(6):1581-1588. doi:10.1016/j.neurobiolaging.2012.12.005.
Nicotinamideriboside restores cognition through an upregulation of proliferator-activated receptor-γ coactivator 1α regulated β-secretase 1 degradation and mitochondrial gene expression in Alzheimer’s mouse models
In the study titled “Nicotinamideriboside restores cognition through an upregulation of proliferator-activated receptor-γ coactivator 1α regulated β-secretase 1 degradation and mitochondrial gene expression in Alzheimer’s mouse models” by Gong et al., the researchers investigated the potential therapeutic effects of nicotinamideriboside (NR) on cognition in Alzheimer’s disease (AD) mouse models. The study revealed that NR supplementation improved cognitive function in AD mice by upregulating the expression of proliferator-activated receptor-γ coactivator 1α (PGC-1α), a key regulator of mitochondrial biogenesis and function. Additionally, NR treatment led to the degradation of β-secretase 1 (BACE1), an enzyme involved in amyloid-β (Aβ) production, and enhanced the expression of mitochondrial genes. These findings suggest that NR may exert neuroprotective effects in AD by enhancing mitochondrial function and reducing Aβ production. The study was published in Neurobiology of Aging in 2013.
Full article on https://www.sciencedirect.com/science/article/pii/S0197458012006203
Matasic DS, Brenner C, London B. Emerging potential benefits of modulating NAD+ metabolism in cardiovascular disease. Am J Physiol Heart Circ Physiol. 2018;314(4):H839-H852. doi:10.1152/ajpheart.00409.2017.
Emerging potential benefits of modulating NAD+ metabolism in cardiovascular disease
In their review article titled “Emerging potential benefits of modulating NAD+ metabolism in cardiovascular disease,” Matasic et al. explore the therapeutic potential of modulating nicotinamide adenine dinucleotide (NAD+) metabolism in cardiovascular disease. They discuss various aspects of NAD+ metabolism, including its role in cellular energetics, redox signaling, and regulation of gene expression. The authors highlight preclinical and clinical studies that suggest NAD+ modulation could offer benefits in the context of cardiovascular diseases such as heart failure, ischemic heart disease, and vascular dysfunction. They also discuss potential mechanisms underlying the cardioprotective effects of NAD+ modulation, including improvements in mitochondrial function, oxidative stress, and inflammation. Overall, the review provides insights into the emerging role of NAD+ metabolism as a therapeutic target for cardiovascular disease. The article was published in the American Journal of Physiology – Heart and Circulatory Physiology in 2018.
Full article on https://journals.physiology.org/doi/abs/10.1152/ajpheart.00409.2017
Alano CC, Tran A, Tao R, Ying W, Karliner JS, Swanson RA. Differences among cell types in NAD+ compartmentalization: a comparison of neurons, astrocytes, and cardiac myocytes. J Neurosci Res 85: 3378–3385, 2007. doi:10.1002/jnr.21479.
Differences among cell types in NAD+ compartmentalization: A comparison of neurons, astrocytes, and cardiac myocytes
In their study titled “Differences among cell types in NAD+ compartmentalization: a comparison of neurons, astrocytes, and cardiac myocytes,” Alano et al. investigated the variations in nicotinamide adenine dinucleotide (NAD+) compartmentalization among different cell types, including neurons, astrocytes, and cardiac myocytes. The researchers utilized a combination of biochemical assays and fluorescence imaging techniques to assess NAD+ levels and distribution within these cell types. Their findings revealed significant differences in NAD+ levels and compartmentalization patterns among the three cell types studied. Specifically, neurons exhibited higher levels of NAD+ compared to astrocytes and cardiac myocytes, and NAD+ distribution within cellular compartments varied across cell types. These results provide insights into the unique metabolic characteristics of different cell types and underscore the importance of understanding NAD+ metabolism in the context of cellular physiology and pathology. The study was published in the Journal of Neuroscience Research in 2007.
Full article on https://onlinelibrary.wiley.com/doi/abs/10.1002/jnr.21479
de Picciotto NE, Gano LB, Johnson LC, Martens CR, Sindler AL, Mills KF, Imai S, Seals DR. Nicotinamide mononucleotide supplementation reverses vascular dysfunction and oxidative stress with aging in mice. Aging Cell 15: 522–530, 2016. doi:10.1111/acel.12461.
Nicotinamide mononucleotide supplementation reverses vascular dysfunction and oxidative stress with aging in mice
In their study titled “Nicotinamide mononucleotide supplementation reverses vascular dysfunction and oxidative stress with aging in mice,” de Picciotto et al. investigated the effects of nicotinamide mononucleotide (NMN) supplementation on vascular function and oxidative stress in aging mice. The researchers administered NMN to aged mice and assessed various parameters related to vascular health, including endothelial function, oxidative stress markers, and mitochondrial function. Their findings demonstrated that NMN supplementation effectively reversed age-related vascular dysfunction and oxidative stress in mice. Specifically, NMN-treated mice exhibited improved endothelial function, reduced oxidative stress levels, and enhanced mitochondrial function compared to untreated aged mice. These results suggest that NMN supplementation may represent a promising strategy for combating age-related vascular impairments and oxidative stress. The study was published in Aging Cell in 2016.
Full article on https://onlinelibrary.wiley.com/doi/abs/10.1111/acel.12461
Alano CC, Tran A, Tao R, Ying W, Karliner JS, Swanson RA. Differences among cell types in NAD+ compartmentalization: a comparison of neurons, astrocytes, and cardiac myocytes. J Neurosci Res 85: 3378–3385, 2007. doi:10.1002/jnr.21479.
Differences among cell types in NAD+ compartmentalization: A comparison of neurons, astrocytes, and cardiac myocytes
In their study titled “Differences among cell types in NAD+ compartmentalization: a comparison of neurons, astrocytes, and cardiac myocytes,” Alano et al. investigated the variations in nicotinamide adenine dinucleotide (NAD+) compartmentalization among different cell types, including neurons, astrocytes, and cardiac myocytes. The researchers utilized a combination of biochemical assays and fluorescence imaging techniques to assess NAD+ levels and distribution within these cell types. Their findings revealed significant differences in NAD+ levels and compartmentalization patterns among the three cell types studied. Specifically, neurons exhibited higher levels of NAD+ compared to astrocytes and cardiac myocytes, and NAD+ distribution within cellular compartments varied across cell types. These results provide insights into the unique metabolic characteristics of different cell types and underscore the importance of understanding NAD+ metabolism in the context of cellular physiology and pathology. The study was published in the Journal of Neuroscience Research in 2007.
Full article on https://onlinelibrary.wiley.com/doi/abs/10.1002/jnr.21479
Liu L, Wang P, Liu X, He D, Liang C, Yu Y. Exogenous NAD(+) supplementation protects H9c2 cardiac myoblasts against hypoxia/reoxygenation injury via Sirt1-p53 pathway. FundamClinPharmacol. 2014;28(2):180-189. doi:10.1111/fcp.12016.
Exogenous NAD+ supplementation protects H9c2 cardiac myoblasts against hypoxia/reoxygenation injury via Sirt1‐p53 pathway
In their study titled “Exogenous NAD(+) supplementation protects H9c2 cardiac myoblasts against hypoxia/reoxygenation injury via Sirt1-p53 pathway,” Liu et al. investigated the protective effects of exogenous NAD(+) supplementation on H9c2 cardiac myoblasts subjected to hypoxia/reoxygenation injury. They explored the involvement of the Sirt1-p53 pathway in mediating these protective effects. The researchers found that NAD(+) supplementation exerted a protective effect against hypoxia/reoxygenation injury in H9c2 cells by activating the Sirt1-p53 pathway, leading to decreased apoptosis and improved cell survival. These findings suggest a potential therapeutic strategy for mitigating cardiac injury through NAD(+) supplementation. This study, published in Fundamental & Clinical Pharmacology in 2014, provides valuable insights into the role of NAD(+) in protecting cardiac cells from ischemic injury.
Full article on https://onlinelibrary.wiley.com/doi/abs/10.1111/fcp.12016
Ryu D, Zhang H, Ropelle ER, Sorrentino V, Mazala DA, Mouchiroud L, Marshall PL, Campbell MD, Ali AS, Knowels GM, et al. NAD+ repletion improves muscle function in muscular dystrophy and counters global PARylation. SciTransl Med. 2016;8:361ra139.
NAD+ repletion improves muscle function in muscular dystrophy and counters global PARylation
In their study titled “NAD+ repletion improves muscle function in muscular dystrophy and counters global PARylation,” Ryu et al. investigated the therapeutic potential of NAD+ repletion in improving muscle function in muscular dystrophy and its effects on global PARylation. Using mouse models of muscular dystrophy, they demonstrated that NAD+ repletion improved muscle function, including grip strength and treadmill endurance, while also reducing muscle damage and inflammation. Furthermore, NAD+ supplementation decreased global PARylation, a process associated with DNA damage and cellular dysfunction. These findings suggest that NAD+ repletion could serve as a promising therapeutic approach for treating muscular dystrophy and potentially other muscle-related disorders. Published in Science Translational Medicine in 2016, this study sheds light on the importance of NAD+ metabolism in muscle health and disease.
Full article on https://www.science.org/doi/abs/10.1126/scitranslmed.aaf5504
Xu W, Barrientos T, Mao L, Rockman HA, Sauve AA, Andrews NC. Lethal Cardiomyopathy in Mice Lacking Transferrin Receptor in the Heart. Cell Rep. 2015;13:533–545.
Lethal cardiomyopathy in mice lacking transferrin receptor in the heart
In their study titled “Lethal Cardiomyopathy in Mice Lacking Transferrin Receptor in the Heart,” Xu et al. investigated the role of the transferrin receptor (TfR) in cardiac function using a mouse model lacking TfR specifically in the heart. They found that mice lacking TfR in the heart developed lethal cardiomyopathy characterized by cardiac hypertrophy, fibrosis, and dysfunction. The researchers observed impaired mitochondrial function, increased oxidative stress, and altered iron metabolism in the hearts of these mice. Additionally, they demonstrated that nicotinamide mononucleotide (NMN) supplementation rescued the cardiomyopathy phenotype in these mice, suggesting a potential therapeutic strategy for cardiac diseases associated with TfR dysfunction. This study, published in Cell Reports in 2015, highlights the critical role of TfR and iron metabolism in maintaining cardiac health and provides insights into potential therapeutic interventions for cardiomyopathy.
Full article on https://www.cell.com/cell-reports/pdf/S2211-1247(15)01034-7.pdf
Chan PK, Torres R, Yandim C, Law PP, Khadayate S, Mauri M, Grosan C, Chapman-Rothe N, Giunti P, Pook M, et al. Heterochromatinization induced by GAA-repeat hyperexpansion in Friedreich’s ataxia can be reduced upon HDAC inhibition by vitamin B3. Hum Mol Genet. 2013;22:2662–2675.
Heterochromatinization induced by GAA-repeat hyperexpansion in Friedreich’s ataxia can be reduced upon HDAC inhibition by vitamin B3
In their study titled “Heterochromatinization induced by GAA-repeat hyperexpansion in Friedreich’s ataxia can be reduced upon HDAC inhibition by vitamin B3,” Chan et al. investigated the role of histone deacetylase (HDAC) inhibition by vitamin B3 in alleviating heterochromatinization caused by GAA-repeat hyperexpansion in Friedreich’s ataxia (FRDA). FRDA is a neurodegenerative disorder caused by the expansion of GAA repeats in the frataxin gene, leading to heterochromatin formation and transcriptional silencing. Using cell and mouse models of FRDA, the researchers demonstrated that HDAC inhibition with vitamin B3 (nicotinamide) reduced heterochromatinization, increased frataxin gene expression, and ameliorated disease phenotypes. Their findings suggest a potential therapeutic strategy for FRDA by targeting epigenetic modifications associated with GAA-repeat expansion, highlighting the role of vitamin B3 as a potential treatment for this debilitating disorder. This study, published in Human Molecular Genetics in 2013, provides insights into the epigenetic mechanisms underlying FRDA pathogenesis and offers a promising avenue for therapeutic intervention.
Full article on https://academic.oup.com/hmg/article-abstract/22/13/2662/609079
Martin AS, Abraham DM, Hershberger KA, Bhatt DP, Mao L, Cui H, Liu J, Liu X, Muehlbauer MJ, Grimsrud PA, et al. Nicotinamide mononucleotide requires SIRT3 to improve cardiac function and bioenergetics in a Friedreich’s ataxia cardiomyopathy model. JCI Insight. 2017;2.
Nicotinamide mononucleotide requires SIRT3 to improve cardiac function and bioenergetics in a Friedreich’s ataxia cardiomyopathy model
In their study titled “Nicotinamide mononucleotide requires SIRT3 to improve cardiac function and bioenergetics in a Friedreich’s ataxia cardiomyopathy model,” Martin et al. investigated the therapeutic potential of nicotinamide mononucleotide (NMN) in improving cardiac function and bioenergetics in a model of Friedreich’s ataxia (FRDA) cardiomyopathy. FRDA is a neurodegenerative disorder caused by GAA-repeat expansion in the frataxin gene, leading to mitochondrial dysfunction and cardiomyopathy. Using a mouse model of FRDA cardiomyopathy, the researchers found that NMN supplementation improved cardiac function and mitochondrial bioenergetics. They further demonstrated that these beneficial effects of NMN were dependent on sirtuin 3 (SIRT3), a mitochondrial deacetylase known to regulate mitochondrial function and metabolism. Their findings suggest that NMN supplementation, through activation of SIRT3, may represent a promising therapeutic strategy for treating cardiac dysfunction in FRDA. This study, published in JCI Insight in 2017, sheds light on the potential role of NMN and SIRT3 in mitigating mitochondrial dysfunction and cardiomyopathy associated with FRDA, highlighting a novel avenue for therapeutic intervention in this debilitating disorder.
Full article on https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5518566/
Katsyuba, E., Romani, M., Hofer, D. et al. NAD+ homeostasis in health and disease. Nat Metab 2, 9–31 (2020). https://doi.org/10.1038/s42255-019-0161-5.
NAD+ homeostasis in health and disease
In their comprehensive review titled “NAD+ homeostasis in health and disease,” Katsyuba et al. provide an overview of the critical role of nicotinamide adenine dinucleotide (NAD+) in various cellular processes and its implications for health and disease. The review discusses the diverse functions of NAD+ as a cofactor for enzymes involved in energy metabolism, DNA repair, signaling pathways, and epigenetic regulation. The authors highlight the importance of maintaining NAD+ homeostasis for cellular function and organismal health, emphasizing the intricate balance between NAD+ synthesis, consumption, and degradation. Furthermore, the review discusses the dysregulation of NAD+ metabolism in aging and age-related diseases, including metabolic disorders, neurodegenerative diseases, and cancer. The authors also explore emerging therapeutic strategies targeting NAD+ metabolism to mitigate age-related decline and treat various diseases. Overall, this review provides valuable insights into the multifaceted roles of NAD+ in physiology and pathology, underscoring its potential as a target for therapeutic intervention in human health and disease. Published in Nature Metabolism in 2020, this review serves as a comprehensive resource for researchers and clinicians interested in NAD+ biology and its implications for healthspan and lifespan.
Full article on https://www.nature.com/articles/s42255-019-0161-5
Walker MA, Tian R. Raising NAD in Heart Failure: Time to Translate?. Circulation. 2018;137(21):2274-2277. doi:10.1161/CIRCULATIONAHA.117.032626.
Raising NAD in heart failure: time to translate?
In their editorial “Raising NAD in Heart Failure: Time to Translate?” published in Circulation in 2018, Walker and Tian discuss the potential therapeutic implications of raising nicotinamide adenine dinucleotide (NAD+) levels in heart failure. They highlight recent preclinical studies demonstrating that NAD+ augmentation can improve cardiac function and mitigate pathological remodeling in heart failure models. The authors underscore the need for translational research to evaluate the efficacy and safety of NAD+ augmentation strategies in human heart failure patients. They emphasize the importance of elucidating the mechanisms underlying NAD+ dysregulation in heart failure and identifying optimal interventions to restore NAD+ homeostasis. Furthermore, Walker and Tian discuss the challenges associated with NAD+ supplementation, including route of administration, dose optimization, and potential off-target effects. Despite these challenges, they advocate for further investigation into NAD+ modulation as a promising therapeutic approach for heart failure. Overall, the editorial provides a critical overview of the current understanding of NAD+ biology in heart failure and highlights the opportunities and challenges in translating preclinical findings into clinical practice.
Full article on https://www.ahajournals.org/doi/abs/10.1161/CIRCULATIONAHA.117.032626
Airhart SE, Shireman LM, Risler LJ, et al. An open-label, non-randomized study of the pharmacokinetics of the nutritional supplement nicotinamideriboside (NR) and its effects on blood NAD+ levels in healthy volunteers. PLoS One. 2017;12(12):e0186459. Published 2017 Dec 6. doi:10.1371/journal.pone.0186459.
An open-label, non-randomized study of the pharmacokinetics of the nutritional supplement nicotinamideriboside (NR) and its effects on blood NAD+ levels in healthy volunteers
In their study published in PLoS One in 2017, Airhart et al. conducted an open-label, non-randomized investigation to evaluate the pharmacokinetics of nicotinamide riboside (NR), a nutritional supplement, and its impact on blood nicotinamide adenine dinucleotide (NAD+) levels in healthy volunteers. The study aimed to characterize the absorption, distribution, metabolism, and excretion of NR, as well as its effect on NAD+ levels, to better understand its potential as a therapeutic agent. The researchers found that NR supplementation led to a significant increase in blood NAD+ levels, indicating its potential to boost NAD+ levels in humans. Moreover, they observed that NR was well-tolerated with no serious adverse effects reported during the study. Overall, the findings suggest that NR supplementation could be a promising strategy for NAD+ augmentation in humans, although further research is needed to explore its therapeutic potential in various health conditions.
Full article on https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0186459
Lee CF, Caudal A, Abell L, NaganaGowda GA, Tian R. Targeting NAD+ Metabolism as Interventions for Mitochondrial Disease. Sci Rep. 2019;9(1):3073. Published 2019 Feb 28. doi:10.1038/s41598-019-39419-4.
Targeting NAD+ Metabolism as Interventions for Mitochondrial Disease
In their study published in Scientific Reports in 2019, Lee et al. investigated the potential of targeting nicotinamide adenine dinucleotide (NAD+) metabolism as interventions for mitochondrial disease. Mitochondrial diseases are a group of disorders characterized by dysfunctional mitochondria, which play a crucial role in cellular energy production. The researchers explored the therapeutic implications of modulating NAD+ metabolism, a key regulator of cellular energy metabolism and mitochondrial function. They discussed various strategies to enhance NAD+ levels, including supplementation with NAD+ precursors such as nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), as well as activation of NAD+-dependent enzymes like sirtuins. By targeting NAD+ metabolism, these interventions aim to improve mitochondrial function and mitigate the symptoms of mitochondrial disease. The study underscores the potential of NAD+ modulation as a promising therapeutic approach for mitochondrial disorders, although further research is needed to validate its efficacy and safety in clinical settings.
Full article on https://www.nature.com/articles/s41598-019-39419-4
Zhou, B., Wang, D. D., Qiu, Y., Airhart, S., Liu, Y., Stempien-Otero, A., O’Brien, K. D., & Tian, R. (2020). Boosting NAD level suppresses inflammatory activation of PBMCs in heart failure. The Journal of clinical investigation, 130(11), 6054–6063. https://doi.org/10.1172/JCI138538.
Boosting NAD level suppresses inflammatory activation of PBMCs in heart failure
In their study published in The Journal of Clinical Investigation in 2020, Zhou et al. investigated the effects of boosting nicotinamide adenine dinucleotide (NAD+) levels on the inflammatory activation of peripheral blood mononuclear cells (PBMCs) in heart failure. The researchers explored the potential of NAD+ supplementation as a therapeutic strategy to modulate inflammation, a key pathological process in heart failure. Using in vitro and in vivo models, they demonstrated that increasing NAD+ levels suppressed the inflammatory activation of PBMCs, leading to reduced production of pro-inflammatory cytokines. Furthermore, they identified the NAD+-dependent enzyme SIRT1 as a critical regulator of this anti-inflammatory effect. These findings suggest that NAD+ augmentation may serve as a novel approach to mitigate inflammation and its detrimental effects in heart failure. The study highlights the therapeutic potential of targeting NAD+ metabolism to modulate immune responses and improve outcomes in cardiovascular disease.
Full article on https://www.jci.org/articles/view/138538?elqTrackId=3664741b67b14ebc884145b2d7d8971b
Hsu, C. P., Oka, S., Shao, D., Hariharan, N., & Sadoshima, J. (2009). Nicotinamide phosphoribosyltransferase regulates cell survival through NAD+ synthesis in cardiac myocytes. Circulation research, 105(5), 481–491. https://doi.org/10.1161/CIRCRESAHA.109.203703.
Nicotinamide Phosphoribosyltransferase Regulates Cell Survival Through NAD+ Synthesis in Cardiac Myocytes
In their 2009 study published in Circulation Research, Hsu et al. investigated the role of nicotinamide phosphoribosyltransferase (NAMPT) in regulating cell survival through nicotinamide adenine dinucleotide (NAD+) synthesis in cardiac myocytes. They demonstrated that NAMPT, the rate-limiting enzyme in the salvage pathway of NAD+ synthesis, plays a critical role in maintaining cellular NAD+ levels and promoting cell survival. Using both in vitro and in vivo models, the researchers showed that genetic manipulation of NAMPT expression affected NAD+ levels and influenced the susceptibility of cardiac myocytes to stress-induced cell death. Specifically, overexpression of NAMPT increased NAD+ levels and protected cardiac myocytes against apoptosis, while NAMPT inhibition had the opposite effect. These findings suggest that NAMPT-mediated NAD+ synthesis is essential for maintaining cardiac myocyte viability and protecting against cell death under pathological conditions. The study sheds light on the mechanistic link between NAD+ metabolism and cell survival in the heart, highlighting NAMPT as a potential therapeutic target for cardiovascular diseases.
Full article on https://www.ahajournals.org/doi/abs/10.1161/CIRCRESAHA.109.203703
Karamanlidis, G., Lee, C. F., Garcia-Menendez, L., Kolwicz, S. C., Jr, Suthammarak, W., Gong, G., Sedensky, M. M., Morgan, P. G., Wang, W., & Tian, R. (2013). Mitochondrial complex I deficiency increases protein acetylation and accelerates heart failure. Cell metabolism, 18(2), 239–250. https://doi.org/10.1016/j.cmet.2013.07.002.
Mitochondrial complex I deficiency increases protein acetylation and accelerates heart failure
In their 2013 study published in Cell Metabolism, Karamanlidis et al. investigated the impact of mitochondrial complex I deficiency on protein acetylation and the progression of heart failure. Using a mouse model with cardiac-specific deletion of the mitochondrial complex I subunit Ndufs4, they demonstrated that complex I deficiency leads to impaired mitochondrial function, increased protein acetylation, and accelerated heart failure progression. The researchers found that the imbalance between NAD+ and NADH levels resulting from complex I deficiency led to decreased activity of the NAD+-dependent deacetylase enzyme SIRT3, which normally regulates protein acetylation in the heart. Consequently, increased protein acetylation occurred in the hearts of mice lacking Ndufs4, contributing to mitochondrial dysfunction, metabolic abnormalities, and the development of heart failure. These findings provide insights into the molecular mechanisms linking mitochondrial dysfunction, protein acetylation, and heart failure pathogenesis, highlighting potential therapeutic targets for mitigating cardiac dysfunction associated with mitochondrial diseases.
Full article on https://www.cell.com/cell-metabolism/pdf/S1550-4131(13)00291-X.pdf
Pillai, J. B., Isbatan, A., Imai, S., & Gupta, M. P. (2005). Poly(ADP-ribose) polymerase-1-dependent cardiac myocyte cell death during heart failure is mediated by NAD+ depletion and reduced Sir2alpha deacetylase activity. The Journal of biological chemistry, 280(52), 43121–43130. https://doi.org/10.1074/jbc.M506162200.
Poly(ADP-ribose) polymerase-1-dependent cardiac myocyte cell death during heart failure is mediated by NAD+ depletion and reduced Sir2alpha deacetylase activity
In their 2005 study published in The Journal of Biological Chemistry, Pillai et al. investigated the role of poly(ADP-ribose) polymerase-1 (PARP-1) in cardiac myocyte cell death during heart failure. They found that PARP-1 activation in response to oxidative stress led to excessive poly(ADP-ribosyl)ation, resulting in NAD+ depletion and reduced activity of the NAD+-dependent deacetylase enzyme Sir2α (SIRT1). The decrease in Sir2α activity, in turn, led to dysregulation of gene expression and increased susceptibility to cell death in cardiac myocytes. The researchers demonstrated that inhibition of PARP-1 activity or augmentation of NAD+ levels could prevent Sir2α inhibition and protect cardiac myocytes from oxidative stress-induced cell death. These findings elucidate the molecular mechanisms underlying PARP-1-mediated cell death in heart failure and highlight the therapeutic potential of targeting NAD+ metabolism to mitigate cardiac dysfunction.
Full article on https://www.jbc.org/article/S0021-9258(19)47925-8/abstract
Yamamoto, T., Byun, J., Zhai, P., Ikeda, Y., Oka, S., & Sadoshima, J. (2014). Nicotinamide mononucleotide, an intermediate of NAD+ synthesis, protects the heart from ischemia and reperfusion. PloS one, 9(6), e98972. https://doi.org/10.1371/journal.pone.0098972.
Nicotinamide mononucleotide, an intermediate of NAD+ synthesis, protects the heart from ischemia and reperfusion
In their 2014 study published in PLOS ONE, Yamamoto et al. explored the protective effects of nicotinamide mononucleotide (NMN), an intermediate of NAD+ synthesis, on the heart during ischemia and reperfusion injury. Using a mouse model of myocardial infarction, they found that treatment with NMN significantly reduced infarct size and improved cardiac function following ischemia and reperfusion. Mechanistically, NMN administration increased NAD+ levels in the heart and activated the NAD+-dependent enzyme SIRT1, leading to deacetylation and activation of the transcription factor FoxO1. Activation of FoxO1 by NMN conferred cardioprotective effects by upregulating antioxidant and anti-apoptotic genes. These findings suggest that NMN supplementation may serve as a potential therapeutic strategy for mitigating ischemia-reperfusion injury in the heart by preserving NAD+ levels and activating SIRT1-mediated signaling pathways.
Full article on https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0098972
Mattagajasingh, I., Kim, C. S., Naqvi, A., Yamamori, T., Hoffman, T. A., Jung, S. B., DeRicco, J., Kasuno, K., & Irani, K. (2007). SIRT1 promotes endothelium-dependent vascular relaxation by activating endothelial nitric oxide synthase. Proceedings of the National Academy of Sciences of the United States of America, 104(37), 14855–14860. https://doi.org/10.1073/pnas.0704329104.
SIRT1 promotes endothelium-dependent vascular relaxation by activating endothelial nitric oxide synthase
In their 2007 study published in the Proceedings of the National Academy of Sciences of the United States of America, Mattagajasingh et al. investigated the role of SIRT1 in endothelium-dependent vascular relaxation. Using both in vitro and in vivo models, they demonstrated that SIRT1 activation promotes endothelial nitric oxide synthase (eNOS) activity and nitric oxide (NO) production in endothelial cells. Mechanistically, they found that SIRT1 directly interacts with and deacetylates eNOS, leading to its activation and subsequent NO-mediated vascular relaxation. Moreover, they showed that SIRT1-mediated deacetylation of eNOS is essential for maintaining vascular homeostasis and preventing endothelial dysfunction under conditions of oxidative stress. These findings highlight the importance of SIRT1 in regulating endothelial function and suggest its potential as a therapeutic target for cardiovascular diseases associated with endothelial dysfunction.
Full article on https://www.pnas.org/doi/abs/10.1073/pnas.0704329104
Uddin, G. M., Youngson, N. A., Doyle, B. M., Sinclair, D. A., and Morris, M. J. (2017). Nicotinamide mononucleotide (NMN) supplementation ameliorates the impact of maternal obesity in mice: comparison with exercise. Sci. Rep. 7:15063. doi: 10.1038/s41598-017-14866-z.
Nicotinamide mononucleotide (NMN) supplementation ameliorates the impact of maternal obesity in mice: comparison with exercise
In their 2017 study published in Scientific Reports, Uddin et al. investigated the effects of nicotinamide mononucleotide (NMN) supplementation on the offspring of obese mothers in mice, comparing it with the effects of exercise. The researchers aimed to assess whether NMN supplementation could mitigate the negative impacts of maternal obesity on offspring health.
The study involved female mice fed either a normal diet or a high-fat diet to induce obesity before mating. Half of the obese mice were given NMN in their drinking water during pregnancy and lactation, while the other half remained untreated. Additionally, a subset of obese mice were subjected to exercise on a wheel during pregnancy and lactation. The offspring were assessed for various metabolic parameters and gene expression related to metabolism and aging.
Full article on https://www.nature.com/articles/s41598-017-14866-z
Porter LC, Franczyk MP, Pietka T, et al. NAD+-dependent deacetylase SIRT3 in adipocytes is dispensable for maintaining normal adipose tissue mitochondrial function and whole body metabolism. Am J PhysiolEndocrinolMetab. 2018;315(4):E520-E530. doi:10.1152/ajpendo.00057.2018.
NAD+-dependent deacetylase SIRT3 in adipocytes is dispensable for maintaining normal adipose tissue mitochondrial function and whole body metabolism
In their 2018 study published in the American Journal of Physiology – Endocrinology and Metabolism, Porter et al. investigated the role of the NAD+-dependent deacetylase SIRT3 in adipocytes and its impact on adipose tissue mitochondrial function and whole-body metabolism. SIRT3 is known to play a crucial role in regulating mitochondrial function and metabolism in various tissues, but its specific role in adipocytes was unclear.
To address this, the researchers generated adipocyte-specific SIRT3 knockout mice and assessed their metabolic phenotypes compared to control mice. They examined adipose tissue mitochondrial function, whole-body metabolism, energy expenditure, glucose and lipid metabolism, and insulin sensitivity in both groups of mice.
Surprisingly, the study found that adipocyte-specific deletion of SIRT3 did not significantly alter adipose tissue mitochondrial function. Additionally, whole-body metabolism, energy expenditure, glucose and lipid metabolism, and insulin sensitivity were largely unaffected by the absence of SIRT3 in adipocytes.
Full article on https://journals.physiology.org/doi/abs/10.1152/ajpendo.00057.2018
Martens CR, Denman BA, Mazzo MR, et al. Chronic nicotinamideriboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults. Nat Commun. 2018;9(1):1286. Published 2018 Mar 29. doi:10.1038/s41467-018-03421-7.
Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults
In their 2018 study published in Nature Communications, Martens et al. investigated the effects of chronic nicotinamide riboside (NR) supplementation on nicotinamide adenine dinucleotide (NAD+) levels in healthy middle-aged and older adults. NAD+ is a crucial coenzyme involved in various cellular processes, including metabolism, DNA repair, and cell signaling. NAD+ levels decline with age and have been implicated in age-related metabolic dysfunction and diseases.
The study enrolled 24 healthy middle-aged and older adults and randomly assigned them to receive either placebo or NR supplementation for 6 weeks. The researchers measured blood NAD+ levels and conducted comprehensive metabolic assessments before and after the supplementation period to evaluate the safety and efficacy of NR supplementation.
Full article on https://www.nature.com/articles/s41467-018-03421-7
Yoshino, M., Yoshino, J., Kayser, B. D., Patti, G. J., Franczyk, M. P., Mills, K. F., Sindelar, M., Pietka, T., Patterson, B. W., Imai, S. I., & Klein, S. (2021). Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women. Science (New York, N.Y.), 372(6547), 1224–1229. https://doi.org/10.1126/science.abe9985.
Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women
In their 2021 study published in Science, Yoshino et al. investigated the effects of nicotinamide mononucleotide (NMN) supplementation on muscle insulin sensitivity in prediabetic women. NMN is a precursor of nicotinamide adenine dinucleotide (NAD+), a coenzyme involved in cellular metabolism and energy production. NAD+ levels decline with age and have been associated with age-related metabolic dysfunction, including insulin resistance.
The study enrolled prediabetic women and randomly assigned them to receive either NMN supplementation or placebo for 10 weeks. The researchers measured muscle insulin sensitivity using hyperinsulinemic-euglycemic clamp techniques before and after the supplementation period. Additionally, they assessed various metabolic parameters, including glucose and lipid metabolism, to evaluate the effects of NMN supplementation on metabolic health.
Full article on https://www.science.org/doi/abs/10.1126/science.abe9985
Camacho-Pereira, J., Tarragó, M. G., Chini, C., Nin, V., Escande, C., Warner, G. M., Puranik, A. S., Schoon, R. A., Reid, J. M., Galina, A., & Chini, E. N. (2016). CD38 Dictates Age-Related NAD Decline and Mitochondrial Dysfunction through an SIRT3-Dependent Mechanism. Cell metabolism, 23(6), 1127–1139. https://doi.org/10.1016/j.cmet.2016.05.006.
CD38 dictates age-related NAD decline and mitochondrial dysfunction through an SIRT3-dependent mechanism
In their 2016 study published in Cell Metabolism, Camacho-Pereira et al. investigated the role of CD38 in age-related decline of nicotinamide adenine dinucleotide (NAD+) levels and mitochondrial dysfunction. NAD+ is a coenzyme involved in various cellular processes, including energy metabolism and DNA repair, and its levels decline with aging.
The researchers found that CD38, a multifunctional enzyme known to hydrolyze NAD+, plays a critical role in regulating NAD+ levels and mitochondrial function during aging. Using mouse models, they demonstrated that CD38 expression increases with age and is associated with a decline in NAD+ levels and impaired mitochondrial function in various tissues, including skeletal muscle and liver.
Furthermore, they showed that genetic deletion of CD38 prevents age-related decline in NAD+ levels and mitochondrial dysfunction, leading to improved metabolic health and physical performance in aged mice. Mechanistically, they proposed that CD38-mediated NAD+ hydrolysis impairs the activity of SIRT3, a mitochondrial sirtuin deacetylase known to regulate mitochondrial function and oxidative stress response.
Full article on https://www.cell.com/cell-metabolism/pdf/S1550-4131(16)30224-8.pdf
Escande, C., Nin, V., Price, N. L., Capellini, V., Gomes, A. P., Barbosa, M. T., O’Neil, L., White, T. A., Sinclair, D. A., & Chini, E. N. (2013). Flavonoid apigenin is an inhibitor of the NAD+ ase CD38: implications for cellular NAD+ metabolism, protein acetylation, and treatment of metabolic syndrome. Diabetes, 62(4), 1084–1093. https://doi.org/10.2337/db12-1139.
Flavonoid Apigenin Is an Inhibitor of the NAD+ase CD38: Implications for Cellular NAD+ Metabolism, Protein Acetylation, and Treatment of Metabolic Syndrome
In their 2013 study published in Diabetes, Escande et al. investigated the inhibitory effects of the flavonoid apigenin on the enzyme CD38, which hydrolyzes nicotinamide adenine dinucleotide (NAD+). NAD+ is a critical cofactor involved in various cellular processes, including metabolism, DNA repair, and cell signaling.
The researchers found that apigenin acts as a potent inhibitor of CD38 activity, leading to increased cellular NAD+ levels. Using both in vitro and in vivo experiments, they demonstrated that apigenin treatment resulted in elevated NAD+ levels in cells and tissues. Moreover, they showed that apigenin-mediated inhibition of CD38 led to increased protein acetylation, a post-translational modification involved in the regulation of cellular metabolism and gene expression.
Full article on https://diabetesjournals.org/diabetes/article-abstract/62/4/1084/17887
Koetz, K., Bryl, E., Spickschen, K., O’Fallon, W. M., Goronzy, J. J., & Weyand, C. M. (2000). T cell homeostasis in patients with rheumatoid arthritis. Proceedings of the National Academy of Sciences of the United States of America, 97(16), 9203–9208. https://doi.org/10.1073/pnas.97.16.9203.
T cell homeostasis in patients with rheumatoid arthritis
In their study published in the Proceedings of the National Academy of Sciences of the United States of America, Koetz et al. investigated T cell homeostasis in patients with rheumatoid arthritis (RA). Rheumatoid arthritis, an autoimmune disease characterized by chronic joint inflammation, involves T cells prominently in its pathogenesis. Analyzing peripheral blood samples from RA patients and healthy controls, the researchers found notable differences in T cell subsets. RA patients exhibited an expansion of memory CD4+ T cells, indicative of prior antigen exposure, alongside a reduction in naive CD4+ T cells, which respond to new antigens. Moreover, T cells from RA patients displayed altered expression of activation markers, suggesting ongoing immune activation and inflammation. These findings shed light on the dysregulation of T cell dynamics in rheumatoid arthritis, offering insights that could inform targeted therapeutic approaches for this condition.
Full article on https://www.pnas.org/doi/abs/10.1073/pnas.97.16.9203
Fyhrquist, F., Tiitu, A., Saijonmaa, O., Forsblom, C., Groop, P. H., & FinnDiane Study Group (2010). Telomere length and progression of diabetic nephropathy in patients with type 1 diabetes. Journal of internal medicine, 267(3), 278–286. https://doi.org/10.1111/j.1365-2796.2009.02139.x.
Telomere length and progression of diabetic nephropathy in patients with type 1 diabetes
In their study published in the Journal of Internal Medicine, Fyhrquist et al. investigated the association between telomere length and the progression of diabetic nephropathy in patients with type 1 diabetes. Diabetic nephropathy is a common and serious complication of diabetes characterized by kidney damage and decline in renal function. The researchers conducted a longitudinal analysis within the FinnDiane Study Group cohort, examining telomere length in peripheral blood leukocytes of type 1 diabetes patients with and without diabetic nephropathy. Their results revealed that shorter telomere length at baseline was associated with a higher risk of progression to advanced stages of diabetic nephropathy over the follow-up period. This suggests that telomere length may serve as a potential biomarker for predicting the progression of diabetic nephropathy in type 1 diabetes patients, providing valuable insights into the pathophysiology and management of this debilitating complication.
Full article on https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.2009.02139.x
Testa, R., Olivieri, F., Sirolla, C., Spazzafumo, L., Rippo, M. R., Marra, M., Bonfigli, A. R., Ceriello, A., Antonicelli, R., Franceschi, C., Castellucci, C., Testa, I., & Procopio, A. D. (2011). Leukocyte telomere length is associated with complications of type 2 diabetes mellitus. Diabetic medicine : a journal of the British Diabetic Association, 28(11), 1388–1394. https://doi.org/10.1111/j.1464-5491.2011.03370.x.
Leukocyte telomere length is associated with complications of type 2 diabetes mellitus
In their study published in Diabetic Medicine, Testa et al. explored the association between leukocyte telomere length and complications of type 2 diabetes mellitus (T2DM). They investigated whether telomere length in leukocytes could serve as a potential biomarker for diabetic complications. The researchers conducted a cross-sectional analysis, measuring leukocyte telomere length in a cohort of patients with T2DM and assessing the presence of diabetic complications such as cardiovascular disease, nephropathy, retinopathy, and neuropathy. Their findings revealed that shorter leukocyte telomere length was significantly associated with an increased risk of diabetic complications, suggesting a potential role for telomere length as a predictor of T2DM-related complications. This study contributes valuable insights into the pathophysiology and prognostication of diabetic complications, highlighting the potential utility of telomere length measurements in clinical practice for risk stratification and management of T2DM patients.
Full article on https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1464-5491.2011.03370.x
Niren N. M. (2006). Pharmacologic doses of nicotinamide in the treatment of inflammatory skin conditions: a review. Cutis, 77(1 Suppl), 11–16.
Pharmacologic doses of nicotinamide in the treatment of inflammatory skin conditions: a review
In a review published in Cutis, Niren (2006) evaluated the use of pharmacologic doses of nicotinamide in the treatment of inflammatory skin conditions. Nicotinamide, a form of vitamin B3, has been studied for its anti-inflammatory properties and its potential therapeutic effects on various skin disorders. The review synthesized evidence from clinical trials and case reports to assess the efficacy and safety of nicotinamide supplementation in conditions such as acne, rosacea, and bullous pemphigoid. Overall, the review highlighted promising results supporting the use of nicotinamide as a treatment option for inflammatory skin conditions, citing its ability to modulate immune responses, reduce inflammation, and improve skin barrier function. The findings underscored the potential of nicotinamide as a valuable therapeutic agent in dermatology, although further research is warranted to elucidate its optimal dosing regimens and long-term effects.
Full article on https://europepmc.org/article/med/16871774
Kaneko, S., Wang, J., Kaneko, M., Yiu, G., Hurrell, J. M., Chitnis, T., Khoury, S. J., & He, Z. (2006). Protecting axonal degeneration by increasing nicotinamide adenine dinucleotide levels in experimental autoimmune encephalomyelitis models. The Journal of neuroscience : the official journal of the Society for Neuroscience, 26(38), 9794–9804. https://doi.org/10.1523/JNEUROSCI.2116-06.2006.
Protecting axonal degeneration by increasing nicotinamide adenine dinucleotide levels in experimental autoimmune encephalomyelitis models
In their study published in The Journal of Neuroscience, Kaneko et al. (2006) investigated the potential of increasing nicotinamide adenine dinucleotide (NAD+) levels to protect against axonal degeneration in experimental autoimmune encephalomyelitis (EAE) models, which mimic multiple sclerosis (MS) pathology. The researchers examined the effects of boosting NAD+ levels through various means, including nicotinamide administration and overexpression of the NAD+-synthesizing enzyme NMNAT1, on axonal preservation and neurological function in EAE mice. They found that interventions aimed at increasing NAD+ levels attenuated axonal degeneration, reduced neurological deficits, and promoted neuronal survival in EAE models. These findings suggest that augmenting NAD+ levels may represent a potential therapeutic strategy for protecting against axonal damage and preserving neurological function in MS and related neuroinflammatory disorders.
Full article on https://www.jneurosci.org/content/26/38/9794.short
Damian, D. L., Patterson, C. R., Stapelberg, M., Park, J., Barnetson, R. S., & Halliday, G. M. (2008). UV radiation-induced immunosuppression is greater in men and prevented by topical nicotinamide. The Journal of investigative dermatology, 128(2), 447–454. https://doi.org/10.1038/sj.jid.5701058.
UV radiation-induced immunosuppression is greater in men and prevented by topical nicotinamide
In their study published in The Journal of Investigative Dermatology, Damian et al. (2008) explored the gender-specific differences in UV radiation-induced immunosuppression and the potential protective effects of topical nicotinamide. The researchers investigated the immunomodulatory effects of UV radiation exposure on male and female subjects and evaluated the efficacy of nicotinamide in preventing UV-induced immunosuppression. Their findings revealed that UV radiation-induced immunosuppression was more pronounced in men compared to women. Importantly, topical application of nicotinamide effectively prevented UV-induced immunosuppression in both genders. These results suggest that nicotinamide may serve as a promising agent for mitigating the immunosuppressive effects of UV radiation, highlighting its potential utility in skin protection and prevention of UV-induced immunosuppression-related skin disorders.
Full article on https://www.sciencedirect.com/science/article/pii/S0022202X15337337
Gensler H. L. (1997). Prevention of photoimmunosuppression and photocarcinogenesis by topical nicotinamide. Nutrition and cancer, 29(2), 157–162. https://doi.org/10.1080/01635589709514618.
Prevention of photoimmunosuppression and photocarcinogenesis by topical nicotinamide
In the study published in Nutrition and Cancer by Gensler (1997), the author investigated the potential of topical nicotinamide in preventing photoimmunosuppression and photocarcinogenesis. The research focused on understanding how nicotinamide application could affect the immune response and reduce the risk of skin cancer induced by exposure to ultraviolet (UV) radiation. Through their experiments, Gensler demonstrated that topical nicotinamide effectively prevented photoimmunosuppression, which is the suppression of the immune system caused by UV exposure. Moreover, nicotinamide showed promising results in reducing the risk of photocarcinogenesis, the process of cancer development induced by UV radiation. These findings suggest that nicotinamide may serve as a potential preventive agent against UV-induced skin damage and skin cancer.
Full article on https://www.tandfonline.com/doi/abs/10.1080/01635589709514618
Yiasemides, E., Sivapirabu, G., Halliday, G. M., Park, J., & Damian, D. L. (2009). Oral nicotinamide protects against ultraviolet radiation-induced immunosuppression in humans. Carcinogenesis, 30(1), 101–105. https://doi.org/10.1093/carcin/bgn248.
Oral nicotinamide protects against ultraviolet radiation-induced immunosuppression in humans
In their study published in Carcinogenesis, Yiasemides et al. (2009) investigated the protective effects of oral nicotinamide against ultraviolet (UV) radiation-induced immunosuppression in humans. The research aimed to assess whether oral nicotinamide supplementation could mitigate the immunosuppressive effects of UV exposure, which can increase the risk of skin cancer. Through their experiments, the authors demonstrated that oral nicotinamide administration effectively protected against UV radiation-induced immunosuppression in human volunteers. This protective effect was evidenced by improvements in immune responses following UV exposure in individuals supplemented with nicotinamide compared to those who received a placebo. These findings suggest that oral nicotinamide supplementation may have potential as a protective strategy against the immunosuppressive effects of UV radiation, thereby reducing the risk of skin cancer development.
Full article on https://academic.oup.com/carcin/article-abstract/30/1/101/317331
Omran, H. M., & Almaliki, M. S. (2020). Influence of NAD+ as an ageing-related immunomodulator on COVID 19 infection: A hypothesis. Journal of infection and public health, 13(9), 1196–1201. https://doi.org/10.1016/j.jiph.2020.06.004.
Influence of NAD+ as an ageing-related immunomodulator on COVID 19 infection: A hypothesis
Omran and Almaliki (2020) proposed a hypothesis in the Journal of Infection and Public Health regarding the potential influence of nicotinamide adenine dinucleotide (NAD+) as an aging-related immunomodulator on COVID-19 infection. The authors suggested that NAD+ levels, which decline with age, may play a role in the immune response to COVID-19. They hypothesized that NAD+ supplementation could potentially enhance immune function and mitigate the severity of COVID-19 infection, particularly in older individuals who are more susceptible to severe outcomes. However, further research is needed to investigate the efficacy of NAD+ supplementation as a potential intervention for COVID-19 and its implications for aging-related immune dysfunction.
Full article on https://www.sciencedirect.com/science/article/pii/S1876034120304986
Hiromatsu, Y., Yang, D., Miyake, I., Koga, M., Kameo, J., Sato, M., Inoue, Y., & Nonaka, K. (1998). Nicotinamide decreases cytokine-induced activation of orbital fibroblasts from patients with thyroid-associated ophthalmopathy. The Journal of clinical endocrinology and metabolism, 83(1), 121–124. https://doi.org/10.1210/jcem.83.1.4478.
Nicotinamide decreases cytokine-induced activation of orbital fibroblasts from patients with thyroid-associated ophthalmopathy
Hiromatsu et al. (1998) investigated the effects of nicotinamide on cytokine-induced activation of orbital fibroblasts from patients with thyroid-associated ophthalmopathy (TAO). They found that nicotinamide decreased the activation of orbital fibroblasts induced by cytokines, suggesting a potential therapeutic role for nicotinamide in TAO. The study provided insights into the immunomodulatory effects of nicotinamide and its potential application in managing autoimmune conditions such as TAO.
Full article on https://academic.oup.com/jcem/article-abstract/83/1/121/2865087
Hiromatsu, Y., Sato, M., Tanaka, K., Ishisaka, N., Kamachi, J., & Nonaka, K. (1993). Inhibitory effects of nicotinamide on intercellular adhesion molecule-1 expression on cultured human thyroid cells. Immunology, 80(2), 330–332.
Inhibitory effects of nicotinamide on intercellular adhesion molecule-1 expression on cultured human thyroid cells
Hiromatsu et al. (1993) explored the inhibitory effects of nicotinamide on the expression of intercellular adhesion molecule-1 (ICAM-1) in cultured human thyroid cells. They found that nicotinamide effectively reduced the expression of ICAM-1 on thyroid cells, suggesting a potential anti-inflammatory role for nicotinamide in modulating immune responses. This study provided valuable insights into the immunomodulatory properties of nicotinamide and its potential therapeutic applications in autoimmune thyroid disorders.
Full article on https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1422199/
Silwal P., Shin K., Choi S., Namgung U., Lee C.Y., Heo J.-Y.-Y. Tryptophan negatively regulates IgE-mediated mast cell activation. Korean J Phys Anthropol. 2017;30:53. doi: 10.11637/kjpa.2017.30.2.53.
Tryptophan negatively regulates IgE-mediated mast cell activation
Silwal et al. (2017) investigated the role of tryptophan in regulating IgE-mediated mast cell activation. Their study demonstrated that tryptophan has a negative regulatory effect on mast cell activation triggered by IgE, suggesting a potential mechanism for modulating allergic responses. This finding contributes to our understanding of the complex interactions between dietary components and immune system function, highlighting tryptophan as a potential target for therapeutic interventions in allergic diseases.
Full article on https://synapse.koreamed.org/upload/synapsedata/pdfdata/0107kjpa/kjpa-30-53.pdf
Picard, F., Kurtev, M., Chung, N., Topark-Ngarm, A., Senawong, T., Machado De Oliveira, R., Leid, M., McBurney, M. W., & Guarente, L. (2004). Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-gamma. Nature, 429(6993), 771–776. https://doi.org/10.1038/nature02583.
Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-γ
Picard et al. (2004) investigated the role of Sirtuin 1 (Sirt1) in regulating fat mobilization in white adipocytes. Their study revealed that Sirt1 promotes fat mobilization by repressing the activity of peroxisome proliferator-activated receptor gamma (PPAR-gamma), a key regulator of adipogenesis. By inhibiting PPAR-gamma, Sirt1 enhances the breakdown of fat stores in white adipocytes, leading to increased energy expenditure. This finding sheds light on the molecular mechanisms underlying metabolic regulation and suggests Sirt1 as a potential target for interventions aimed at modulating fat metabolism and combating obesity-related disorders.
Full article on https://www.nature.com/articles/nature02583
Rodgers, J. T., Lerin, C., Haas, W., Gygi, S. P., Spiegelman, B. M., & Puigserver, P. (2005). Nutrient control of glucose homeostasis through a complex of PGC-1alpha and SIRT1. Nature, 434(7029), 113–118. https://doi.org/10.1038/nature03354.
Nutrient control of glucose homeostasis through a complex of PGC-1alpha and SIRT1
Rodgers et al. (2005) explored the molecular mechanisms underlying nutrient control of glucose homeostasis, focusing on the interaction between peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and Sirtuin 1 (SIRT1). They discovered that PGC-1α and SIRT1 form a complex that plays a crucial role in regulating glucose metabolism in response to nutrient availability. Specifically, they found that SIRT1 deacetylates and activates PGC-1α, leading to the induction of genes involved in gluconeogenesis and mitochondrial biogenesis. This study highlights the intricate interplay between nutrient sensing and metabolic regulation, providing insights into the potential therapeutic targets for metabolic disorders such as diabetes.
Full article on https://www.nature.com/articles/nature03354
Yang, F., Vought, B. W., Satterlee, J. S., Walker, A. K., Jim Sun, Z. Y., Watts, J. L., DeBeaumont, R., Saito, R. M., Hyberts, S. G., Yang, S., Macol, C., Iyer, L., Tjian, R., van den Heuvel, S., Hart, A. C., Wagner, G., & Näär, A. M. (2006). An ARC/Mediator subunit required for SREBP control of cholesterol and lipid homeostasis. Nature, 442(7103), 700–704. https://doi.org/10.1038/nature04942.
An ARC/Mediator subunit required for SREBP control of cholesterol and lipid homeostasis
Yang et al. (2006) identified an ARC/Mediator subunit essential for the Sterol Regulatory Element-Binding Protein (SREBP) pathway’s regulation of cholesterol and lipid homeostasis. The study revealed that this subunit, termed ARC105, interacts with the SREBP transcription factors to mediate their transcriptional activity. Through biochemical and genetic analyses in Caenorhabditis elegans and mammalian cells, the authors demonstrated that ARC105 depletion impairs SREBP-mediated lipid metabolism, leading to aberrant cholesterol and lipid levels. This research sheds light on the molecular mechanisms underlying lipid homeostasis regulation and provides potential targets for therapeutic interventions in metabolic diseases associated with dysregulated lipid metabolism.
Full article on https://www.nature.com/articles/nature04942
Remie CME, Roumans KHM, Moonen MPB, et al. Nicotinamideriboside supplementation alters body composition and skeletal muscle acetylcarnitine concentrations in healthy obese humans [published online ahead of print, 2020 Apr 22]. Am J ClinNutr. 2020;nqaa072. doi:10.1093/ajcn/nqaa072.
Nicotinamide riboside supplementation alters body composition and skeletal muscle acetylcarnitine concentrations in healthy obese humans
Remie et al. (2020) conducted a study to investigate the effects of nicotinamide riboside (NR) supplementation on body composition and skeletal muscle acetylcarnitine concentrations in healthy obese individuals. In this randomized, double-blind, placebo-controlled trial, obese participants received either NR supplementation or placebo for 6 weeks. The results showed that NR supplementation led to alterations in body composition, including reductions in fat mass and increases in fat-free mass compared to the placebo group. Additionally, NR supplementation was associated with changes in skeletal muscle acetylcarnitine concentrations. These findings suggest potential metabolic benefits of NR supplementation in obese individuals, highlighting its role in modulating body composition and skeletal muscle metabolism.
Full article on https://academic.oup.com/ajcn/article-abstract/112/2/413/5823793
deGuia RM, Agerholm M, Nielsen TS, et al. Aerobic and resistance exercise training reverses age-dependent decline in NAD+ salvage capacity in human skeletal muscle. Physiol Rep. 2019;7(12):e14139. doi:10.14814/phy2.14139.
Aerobic and resistance exercise training reverses age-dependent decline in NAD+ salvage capacity in human skeletal muscle
In their study published in Physiological Reports in 2019, de Guia et al. investigated the effects of aerobic and resistance exercise training on NAD+ salvage capacity in human skeletal muscle and its potential reversal of age-dependent decline. They conducted a randomized controlled trial involving older adults who underwent either aerobic or resistance exercise training for 12 weeks. The results demonstrated that both forms of exercise training effectively reversed the age-dependent decline in NAD+ salvage capacity in human skeletal muscle. This finding suggests that regular exercise, whether aerobic or resistance-based, can enhance NAD+ metabolism and potentially contribute to the maintenance of muscle health and function with aging.
Full article on https://thescholarship.ecu.edu/bitstream/handle/10342/9809/HoumardAerobicandresistanceexercisetrainingreversesagedependentdecline.pdf?sequence=1
Ryu D, Zhang H, Ropelle ER, et al. NAD+ repletion improves muscle function in muscular dystrophy and counters global PARylation. SciTransl Med. 2016;8(361):361ra139. doi:10.1126/scitranslmed.aaf5504.
NAD+ repletion improves muscle function in muscular dystrophy and counters global PARylation
In their study published in Science Translational Medicine in 2016, Ryu et al. investigated the effects of NAD+ repletion on muscle function in muscular dystrophy and its impact on global PARylation. Using mouse models of muscular dystrophy, they found that NAD+ repletion improved muscle function, increased muscle strength, and reduced muscle damage. Additionally, they observed that NAD+ repletion led to a decrease in global PARylation, suggesting that NAD+ supplementation may modulate poly(ADP-ribose) polymerase (PARP) activity. These findings highlight the potential therapeutic benefits of NAD+ supplementation in treating muscular dystrophy and underscore the importance of NAD+ metabolism in muscle health.
Full article on https://www.science.org/doi/abs/10.1126/scitranslmed.aaf5504
Zhou CC, Yang X, Hua X, et al. Hepatic NAD(+) deficiency as a therapeutic target for non-alcoholic fatty liver disease in ageing. Br J Pharmacol. 2016;173(15):2352-2368. doi:10.1111/bph.13513.
Hepatic NAD+ deficiency as a therapeutic target for non‐alcoholic fatty liver disease in ageing
In their study published in the British Journal of Pharmacology in 2016, Zhou et al. explored the potential of targeting hepatic NAD+ deficiency as a therapeutic strategy for non-alcoholic fatty liver disease (NAFLD) in aging. They investigated the role of NAD+ metabolism in the pathogenesis of NAFLD, particularly focusing on age-related changes in hepatic NAD+ levels. The researchers found that aging is associated with a decline in hepatic NAD+ levels, which contributes to the development and progression of NAFLD. They proposed that restoring NAD+ levels could be a promising therapeutic approach for NAFLD in aging individuals. The study highlights the importance of NAD+ metabolism in liver health and suggests NAD+ supplementation as a potential intervention for NAFLD in the elderly.
Full article on https://bpspubs.onlinelibrary.wiley.com/doi/abs/10.1111/bph.13513
Guarino M, Dufour JF. Nicotinamide and NAFLD: Is There Nothing New Under the Sun?. Metabolites. 2019;9(9):180. Published 2019 Sep 10. doi:10.3390/metabo9090180.
Nicotinamide and NAFLD: Is There Nothing New Under the Sun?
In their review published in Metabolites in 2019, Guarino and Dufour examined the role of nicotinamide in non-alcoholic fatty liver disease (NAFLD). They explored the existing literature to determine whether there were any new insights or developments regarding the use of nicotinamide in NAFLD treatment. The review aimed to provide an updated understanding of the potential benefits and limitations of nicotinamide supplementation for NAFLD management. By synthesizing the available evidence, the authors discussed the mechanisms by which nicotinamide may exert its effects on liver metabolism and inflammation, shedding light on its therapeutic potential in NAFLD.
Full article on https://www.mdpi.com/2218-1989/9/9/180
Wang S, Wan T, Ye M, et al. Nicotinamideriboside attenuates alcohol induced liver injuries via activation of SirT1/PGC-1α/mitochondrial biosynthesis pathway. Redox Biol. 2018;17:89-98. doi:10.1016/j.redox.2018.04.006.
Nicotinamideriboside attenuates alcohol induced liver injuries via activation of SirT1/PGC-1α/mitochondrial biosynthesis pathway
In their study published in Redox Biology in 2018, Wang et al. investigated the potential protective effects of nicotinamide riboside (NR) against alcohol-induced liver injuries. They explored the underlying mechanisms involved in NR’s action, focusing on the activation of the SirT1/PGC-1α/mitochondrial biosynthesis pathway. Using an experimental model of alcohol-induced liver injury, the researchers demonstrated that NR supplementation attenuated liver damage by enhancing mitochondrial function and reducing oxidative stress. Their findings suggested that NR could be a promising therapeutic agent for mitigating alcohol-induced liver injuries through its effects on mitochondrial biogenesis and redox balance.
Full article on https://www.sciencedirect.com/science/article/pii/S2213231718300624
Pham TX, Bae M, Kim MB, et al. Nicotinamideriboside, an NAD+ precursor, attenuates the development of liver fibrosis in a diet-induced mouse model of liver fibrosis. BiochimBiophysActaMol Basis Dis. 2019;1865(9):2451-2463. doi:10.1016/j.bbadis.2019.06.009.
Nicotinamideriboside, an NAD+ precursor, attenuates the development of liver fibrosis in a diet-induced mouse model of liver fibrosis
In their study published in Biochimica et Biophysica Acta Molecular Basis of Disease in 2019, Pham et al. investigated the potential therapeutic effects of nicotinamide riboside (NR), an NAD+ precursor, on liver fibrosis development using a diet-induced mouse model. The researchers found that supplementation with NR attenuated the progression of liver fibrosis by reducing hepatic inflammation, oxidative stress, and fibrotic deposition. They observed improvements in liver function and histological features in mice receiving NR supplementation compared to control mice. The study suggested that NR supplementation may hold promise as a therapeutic strategy for preventing and treating liver fibrosis, possibly through its role in modulating NAD+ metabolism and associated cellular pathways.
Full article on https://www.sciencedirect.com/science/article/pii/S0925443919302029
Han X, Bao X, Lou Q, et al. Nicotinamideriboside exerts protective effect against aging-induced NAFLD-like hepatic dysfunction in mice. PeerJ. 2019;7:e7568. Published 2019 Aug 28. doi:10.7717/peerj.7568.
Nicotinamide riboside exerts protective effect against aging-induced NAFLD-like hepatic dysfunction in mice
In their study published in PeerJ in 2019, Han et al. investigated the protective effects of nicotinamide riboside (NR) against aging-induced non-alcoholic fatty liver disease (NAFLD)-like hepatic dysfunction in mice. The researchers found that NR supplementation exerted a protective effect against aging-induced NAFLD-like hepatic dysfunction by attenuating hepatic lipid accumulation, inflammation, and oxidative stress. They observed improvements in liver function markers and histological features in aged mice receiving NR supplementation compared to control aged mice. The study suggested that NR supplementation may have therapeutic potential for preventing and treating NAFLD-related liver dysfunction associated with aging, possibly through its role in modulating NAD+ metabolism and associated cellular pathways.
Full article on https://peerj.com/articles/7568/
Ralto KM, Rhee EP, Parikh SM. NAD+ homeostasis in renal health and disease. Nat Rev Nephrol. 2020;16(2):99-111. doi:10.1038/s41581-019-0216-6.
NAD+ homeostasis in renal health and disease
In their review published in Nature Reviews Nephrology in 2020, Ralto et al. comprehensively discuss the role of nicotinamide adenine dinucleotide (NAD+) homeostasis in renal health and disease. The authors delve into the molecular mechanisms underlying NAD+ biosynthesis, salvage, and degradation pathways in the kidney, highlighting the importance of NAD+ in maintaining renal function and cellular metabolism. They explore how dysregulation of NAD+ metabolism contributes to the pathogenesis of various renal disorders, including acute kidney injury, chronic kidney disease, and diabetic nephropathy. Furthermore, the review discusses emerging therapeutic strategies targeting NAD+ metabolism for the treatment of kidney diseases, emphasizing the potential of NAD+ precursors and modulators as novel therapeutic interventions to preserve renal function and ameliorate kidney injury.
Full article on https://www.nature.com/articles/s41581-019-0216-6
Hershberger KA, Martin AS, Hirschey MD. Role of NAD+ and mitochondrial sirtuins in cardiac and renal diseases. Nat Rev Nephrol. 2017;13(4):213-225. doi:10.1038/nrneph.2017.5.
Role of NAD+ and mitochondrial sirtuins in cardiac and renal diseases
In their review published in Nature Reviews Nephrology in 2017, Hershberger et al. provide insights into the role of nicotinamide adenine dinucleotide (NAD+) and mitochondrial sirtuins in the pathophysiology of cardiac and renal diseases. The authors discuss the importance of NAD+ as a key cofactor for sirtuin-mediated deacetylation reactions and its role in regulating cellular metabolism, oxidative stress, and mitochondrial function. They explore how dysregulation of NAD+ levels and sirtuin activity contribute to the development and progression of cardiovascular and kidney disorders, including heart failure, ischemic heart disease, diabetic cardiomyopathy, acute kidney injury, and chronic kidney disease. Additionally, the review highlights the therapeutic potential of targeting NAD+ metabolism and sirtuin pathways for the treatment of cardiac and renal diseases, emphasizing the importance of further research in this field to identify novel therapeutic strategies and improve patient outcomes.
Full article on https://www.nature.com/articles/nrneph.2017.5
PoyanMehr A, Parikh SM. PPARγ-Coactivator-1α, Nicotinamide Adenine Dinucleotide and Renal Stress Resistance. Nephron. 2017;137(4):253-255. doi:10.1159/000471895.
PPARγ-coactivator-1α, nicotinamide adenine dinucleotide and renal stress resistance
In their commentary published in Nephron in 2017, Poyan Mehr and Parikh discuss the role of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) and nicotinamide adenine dinucleotide (NAD+) in renal stress resistance. They highlight the importance of PGC-1α in regulating mitochondrial biogenesis, oxidative stress response, and energy metabolism in the kidney. The authors also discuss the role of NAD+ as a key cofactor for PGC-1α activity and its involvement in cellular processes such as DNA repair, apoptosis, and cellular metabolism. They emphasize the potential therapeutic implications of targeting the PGC-1α/NAD+ axis to enhance renal stress resistance and protect against kidney injury in various pathological conditions.
Full article on https://karger.com/nef/article/137/4/253/212156
PoyanMehr A, Tran MT, Ralto KM, et al. De novo NAD+ biosynthetic impairment in acute kidney injury in humans. Nat Med. 2018;24(9):1351-1359. doi:10.1038/s41591-018-0138-z.
De novo NAD+ biosynthetic impairment in acute kidney injury in humans
In their study published in Nature Medicine in 2018, Poyan Mehr et al. investigate the role of de novo nicotinamide adenine dinucleotide (NAD+) biosynthesis in acute kidney injury (AKI) in humans. The researchers demonstrate that AKI is associated with a significant impairment in the de novo biosynthesis of NAD+ in the kidney. They identify key enzymes involved in NAD+ biosynthesis, such as quinolinate phosphoribosyltransferase (QPRT) and nicotinamide phosphoribosyltransferase (NAMPT), as potential targets for therapeutic intervention in AKI. The findings suggest that restoring NAD+ levels through supplementation or targeting NAD+ biosynthetic pathways could be a promising approach for the treatment of AKI and its associated complications.
Full article on https://www.nature.com/articles/s41591-018-0138-z
Zhuo, L., Fu, B., Bai, X., Zhang, B., Wu, L., Cui, J., Cui, S., Wei, R., Chen, X., & Cai, G. (2011). NAD blocks high glucose induced mesangial hypertrophy via activation of the sirtuins-AMPK-mTOR pathway. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology, 27(6), 681–690. https://doi.org/10.1159/000330077
NAD blocks high glucose induced mesangial hypertrophy via activation of the sirtuins-AMPK-mTOR pathway
In their study published in Cellular Physiology and Biochemistry in 2011, Zhuo et al. explored the potential role of nicotinamide adenine dinucleotide (NAD+) in blocking high glucose-induced mesangial hypertrophy. They investigated the underlying molecular mechanisms involving the sirtuins-AMPK-mTOR pathway. The researchers found that NAD+ effectively inhibited mesangial cell hypertrophy induced by high glucose levels. Mechanistically, they observed that NAD+ exerted its protective effects through the activation of sirtuins, AMP-activated protein kinase (AMPK), and inhibition of the mammalian target of rapamycin (mTOR) pathway. This study highlights the potential therapeutic role of NAD+ in preventing mesangial hypertrophy associated with conditions like diabetes mellitus.
Full article on https://karger.com/cpb/article-abstract/27/6/681/318620
Guan, Y., Wang, S. R., Huang, X. Z., Xie, Q. H., Xu, Y. Y., Shang, D., & Hao, C. M. (2017). Nicotinamide Mononucleotide, an NAD+ Precursor, Rescues Age-Associated Susceptibility to AKI in a Sirtuin 1-Dependent Manner. Journal of the American Society of Nephrology : JASN, 28(8), 2337–2352. https://doi.org/10.1681/ASN.2016040385
Nicotinamide mononucleotide, an NAD+ precursor, rescues age-associated susceptibility to AKI in a sirtuin 1–dependent manner
In their study published in the Journal of the American Society of Nephrology in 2017, Guan et al. investigated the potential of nicotinamide mononucleotide (NMN), a precursor of nicotinamide adenine dinucleotide (NAD+), in rescuing age-associated susceptibility to acute kidney injury (AKI). The researchers found that NMN supplementation effectively protected against AKI in aged mice by enhancing renal NAD+ levels. They further demonstrated that the protective effects of NMN were mediated through Sirtuin 1 (SIRT1)-dependent pathways, which include the activation of AMP-activated protein kinase (AMPK) and inhibition of p53-mediated apoptosis. This study provides valuable insights into the role of NAD+ precursors in mitigating age-related kidney dysfunction and suggests NMN as a potential therapeutic agent for AKI.
Full article on https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5533221/
Morigi, M., Perico, L., Rota, C., Longaretti, L., Conti, S., Rottoli, D., Novelli, R., Remuzzi, G., & Benigni, A. (2015). Sirtuin 3-dependent mitochondrial dynamic improvements protect against acute kidney injury. The Journal of clinical investigation, 125(2), 715–726. https://doi.org/10.1172/JCI77632.
Sirtuin 3-dependent mitochondrial dynamic improvements protect against acute kidney injury
In their study published in The Journal of Clinical Investigation in 2015, Morigi et al. investigated the role of Sirtuin 3 (SIRT3), a mitochondrial deacetylase enzyme, in protecting against acute kidney injury (AKI). They demonstrated that SIRT3 plays a crucial role in maintaining mitochondrial dynamics and function in renal tubular cells. Using both in vitro and in vivo models of AKI, the researchers showed that SIRT3 deficiency exacerbated kidney injury, whereas SIRT3 activation or overexpression protected against it. Specifically, SIRT3 activation promoted mitochondrial fusion and fission dynamics, thereby enhancing mitochondrial function and preventing tubular cell death. This study highlights the importance of SIRT3-mediated mitochondrial dynamics in the pathogenesis of AKI and suggests SIRT3 activation as a potential therapeutic strategy for AKI.
Full article on https://www.jci.org/articles/view/77632
Tran, M. T., Zsengeller, Z. K., Berg, A. H., Khankin, E. V., Bhasin, M. K., Kim, W., Clish, C. B., Stillman, I. E., Karumanchi, S. A., Rhee, E. P., & Parikh, S. M. (2016). PGC1α drives NAD biosynthesis linking oxidative metabolism to renal protection. Nature, 531(7595), 528–532. https://doi.org/10.1038/nature17184.
PGC1α drives NAD biosynthesis linking oxidative metabolism to renal protection
In their 2016 study published in Nature, Tran et al. elucidated the role of peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC1α) in driving nicotinamide adenine dinucleotide (NAD) biosynthesis and linking oxidative metabolism to renal protection. The researchers discovered that PGC1α, a master regulator of mitochondrial biogenesis and oxidative metabolism, promotes the expression of key enzymes involved in NAD biosynthesis, including nicotinamide phosphoribosyltransferase (NAMPT). By using genetic and pharmacological approaches in both in vitro and in vivo models, they demonstrated that PGC1α-mediated NAD synthesis is essential for protecting against acute kidney injury (AKI). Specifically, PGC1α-driven NAD biosynthesis preserves mitochondrial function, reduces oxidative stress, and promotes tubular cell survival during AKI. This study highlights the critical role of PGC1α-NAD axis in renal protection and suggests PGC1α activation as a potential therapeutic strategy for AKI and other kidney diseases.
Full article on https://www.nature.com/articles/nature17184
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