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Category: Calorie Restriction

  • Boosting Longevity with NAD+: Insights, Science, and Recommendations

    Aging takes a toll on our cells, making recovery from illness or injury tougher over time. Enter NAD+ (nicotinamide adenine dinucleotide), a powerhouse coenzyme driving DNA repair, energy production, and cellular health. As NAD+ levels drop with age—by up to 50% in some tissues—researchers and longevity enthusiasts are turning to NAD+ boosting therapies to potentially slow aging and enhance vitality. Here’s the scoop on NAD+, its precursors, and what the science says about their role in longevity.

    Why NAD+ Matters

    NAD+ is essential for over 500 cellular processes, from powering mitochondria to activating sirtuins, proteins that regulate aging and health. As we age, NAD+ declines due to increased consumption (e.g., DNA repair) and reduced synthesis, contributing to fatigue, metabolic issues, and disease vulnerability. Boosting NAD+ through precursors—molecules the body converts into NAD+—is a hot topic in longevity circles, promising to restore cellular resilience.

    Harvard longevity expert David Sinclair is a vocal proponent of NAD+ boosting. He argues that NAD+ decline accelerates aging by impairing sirtuins, which maintain cellular health. His groundbreaking mouse studies show that nicotinamide mononucleotide (NMN) restores NAD+ levels, reversing mitochondrial aging and boosting vascular health and lifespan. Sinclair himself takes 1g of NMN daily, paired with resveratrol to enhance sirtuin activity. However, he acknowledges human evidence is still emerging, and his commercial ties to NAD+-related ventures have sparked debate. More human trials are needed to confirm his findings.

    How NAD+ Precursors Work

    NAD+ precursors feed into the body’s salvage pathway, efficiently replenishing NAD+. Here’s a quick look at the key players:

    • Nicotinamide Riboside (NR): Converts to NMN via NRK enzymes, then to NAD+. It boosts muscle NAD+ by ~60%, enhancing energy and reducing inflammation.
    • Nicotinamide Mononucleotide (NMN): One step from NAD+, NMN rapidly raises levels in the liver and brain, improving insulin sensitivity. It may convert to NR for cell entry.
    • Nicotinamide (NAM) & Nicotinic Acid (NA): NAM recycles to NMN, but high doses may inhibit sirtuins. NA forms NaMN but causes flushing.
    • Reduced Precursors (NRH/NMNH): These bypass rate-limiting enzymes for faster NAD+ production but may increase inflammation in some cells.

    Precursors restore NAD+ to support metabolism and repair, though excessive doses risk methylation strain or other side effects.

    The Science So Far

    Mouse studies, including Sinclair’s, show NMN and NR extend lifespan and improve health metrics like endurance and vascular function. Human trials, however, are smaller and less conclusive. NMN (250–500 mg/day) has improved sleep in older adults and insulin sensitivity in prediabetic women, while NR reduces inflammation. Experts like Daniel Craighead and Jonas Thue Treebak caution that evidence for human lifespan extension is thin, with stronger benefits seen in conditions like prediabetes or age-related diseases.

    Longevity Supplementation Trends

    • Popular Choices: NMN (250–1,000 mg/day) or NR (e.g., Tru Niagen, 250–500 mg/day), often paired with resveratrol, metformin, or senolytics like fisetin.
    • Methods: Oral capsules are most common, with sublingual forms for faster absorption. IV infusions ($200–$500/session) are pricier and less studied.
    • Lifestyle Boosts: Fasting, exercise, and low-carb diets enhance NAD+ via NAMPT enzyme activity. X users (e.g., @BiohackerX, July 2025) report mixed results, with some feeling energized and others noticing little change.

    Risks and Considerations

    NAD+ precursors are sold as supplements, often unregulated by the FDA, leading to inconsistent dosages and unverified claims. NMN’s supplement status was questioned in 2022, reclassified as a drug. While short-term use is safe, long-term risks like liver strain or potential cancer promotion (in mice) remain unclear. Side effects include headaches or nausea. Researchers like Eduardo Chini and Joseph Baur suggest NAD+ therapies may better target diseases (e.g., Parkinson’s, heart disease) than general aging, urging caution against overhyped commercial products.

    The NOMIX Take

    At NOMIX, we’re excited about NAD+’s potential but grounded in science. Precursors like NMN and NR show promise, especially for metabolic and cognitive health, but they’re not a magic bullet. Pairing supplementation with healthy habits—exercise, fasting, and a balanced diet—maximizes benefits. Stay curious and cautious: consult your biocoach or doctor, choose reputable brands, and start with low doses.

  • Resveratrol Fails to Deliver: Meta-Analysis Reveals No Benefits on Metabolic Health

    Resveratrol, a polyphenol compound, was touted as an “anti-aging” therapy 20 years ago, but the science behind it has since been discredited.

    Recently, a systematic review and meta-analysis examined the effects of Resveratrol on metabolic health and found no significant benefits compared to placebo. The proposed connection between resveratrol and metabolic health relies on three main concepts:

    1) Resveratrol is bioavailable,

    2) Resveratrol activates sirtuins, and

    3) Sirtuin activation mediates the health and longevity benefits of calorie restriction.

    However, these concepts are not supported by evidence. Resveratrol’s bioavailability is limited, its “sirtuin activating” effects are artificial, and lifespan extension with sirtuin activation in yeast is not reproducible in multicellular organisms.

    In conclusion, the meta-analysis found no significant differences between resveratrol and placebo treatments in effects on triglycerides, total cholesterol, HbA1c, insulin, liver enzymes, or BMI. The results are consistent across the included studies, indicating that Resveratrol offers no evident benefits for metabolic health. Notably, the study’s findings exhibited high consistency across all included trials, reinforcing the validity of the results. The weight of evidence against Resveratrol as an effective treatment or prevention strategy for any indication continues to grow.

    🎧 Listen to our AI-generated deep dive conversation about the Resveratrol meta-analysis!

  • Simplified weight loss for obesity through biofeedback

    For obese people, losing fat mass is a crucial step on the way to better health and life expectancy. However, after the first few pounds have disappeared, the body compensates in various ways to prevent further weight loss – for example, by reducing the metabolic rate and increasing hunger.

    As a result, patients tend to plateau in weight loss before reaching their final goal, as diet and exercise programs that initially showed promise prove ineffective after this early phase. One possible strategy to avoid such a premature plateau is to adjust diet and activity plans based on changes in whole-body energy expenditure over time. A new study sought to investigate whether using energy expenditure biofeedback to inform and adjust weight loss strategies would improve loss of body weight and fat mass compared to standard diet and activity counseling alone.

    In this randomized trial, 52 participants with obesity were counseled by dietitians and instructed to maintain a standard caloric restriction (30% or 500 kcal/day below daily energy requirements, whichever was greater) and at least 150 minutes of physical activity per week during the 24-week study. For half of these participants (INT group), dietitians modified recommendations throughout the study based on energy expenditure information derived from wearable indirect calorimetry devices, while dietitians did not modify recommendations for control participants. At the end of the study, participants in the INT group had lost more weight overall than the control group (-2.3 kg; 95% CI: -3.1 to -1.5; P<0.001) and had a greater reduction in body fat percentage (-1.5%; 95% CI: -2.31 to -0.72; P<0.001).

    In addition, a significantly higher proportion of participants in the INT group achieved a weight loss of at least 5% from baseline than participants in the control group (42% of the INT group versus 8% of the control group; P=0.007). These results suggest that integrating continuous feedback on metabolic changes to personalize and adjust diet and exercise plans may improve the likelihood of avoiding weight plateaus before reaching weight loss goals.

    Biofeedback is a relevant aspect of BIOCOACHING that provides accurate information about the status quo and the change in health status through interventions recommended by the BIOCOACH based on the relevant health and lifestyle data.

  • Direct links between nutrients and epigenetic aging

    As the population ages, the prevalence of age-related diseases is expected to increase significantly, placing a massive burden on healthcare systems and society. To address this issue, it is crucial to promote healthy aging. Biological age, which considers physiological deterioration linked to morbidity and mortality risk, is a more accurate measure of aging than chronological age. This measure is influenced by various factors, including nutritional factors, which have the potential to mitigate the risk of age-related diseases.

    The epigenetic clock, a promising biomarker of biological age, can investigate the direct relations between nutritional factors and aging, identifying potential intervention targets to improve healthy aging.

    While people are living longer, morbidity rates are expected to rise further as aging is a primary risk factor for common diseases like cancer and cardiovascular disease. This will have major healthcare, economic, and social implications, emphasizing the importance of healthy aging. However, not everyone ages at the same rate in terms of their health status and susceptibility to disease and death. Biological age, which considers the degree of physiological deterioration over time, represents aging more accurately and is a better predictor of morbidity and mortality.

    Research suggests that a complex interplay between lifestyle and genetics influences aging, with genetics accounting for a variable but significant percentage of lifespan variation in the population. Alongside genome-wide analyses that have identified measurable genetic effects on the aging rate, lifestyle factors have been proposed to play a more significant role in determining the pace of aging. In particular, nutritional factors like dietary fiber and omega-3 fatty acids, along with a physically active lifestyle, have been reported to mitigate age-related disease risk and may have the potential to improve healthy aging.

    To determine factors associated with accelerated or decelerated aging rates, researchers have been studying clinical biomarkers that can accurately reflect biological age. The epigenetic clock, which estimates biological age based on the cumulative assessment of DNA methylation at age-related CpG-sites, stands out as the currently most accurate measure of biological age and a strong predictor of both mortality and morbidity. With epigenetic clocks, epigenetic age acceleration can be calculated, which is associated with multiple age-related conditions, whereas epigenetic age deceleration is associated with lifestyle factors like a healthy diet and physical activity.

    This study aims to discover the interactive network between nutrients and epigenetic age acceleration by using Copula Graphical Models (CGM), a network analysis method that can cope with multiple types of data as well as complex inter-nutrient relationships without subjective selection of confounders.

    The study used a data-driven approach to identify nutrients that relate to decelerated biological aging. Several direct relationships were revealed, including:

    • Negative associations between PhenoAge acceleration and dietary intakes of coumestrol, beta-carotene, and arachidic acid.
    • Positive associations between PhenoAge acceleration and dietary intakes of added sugar, gondoic acid, arachidonic acid, behenic acid, and vitamin A.
    • Associations between PhenoAge acceleration and lifestyle factors, such as smoking, BMI, WHR, and blood pressure.

    The study highlights the importance of considering individual nutrients and their sources, rather than broad categories when studying their effects on aging.

  • The Impact of NMN, NAD+, and NR, on Longevity

    Nicotinamide adenine dinucleotide, or NAD+, is a crucial molecule found in every cell of our body. It’s like a spark plug that helps power various essential processes, such as fixing DNA damage, controlling gene activity, producing energy, and regulating calcium levels. NAD+ levels tend to increase when our energy levels are low, like during fasting, calorie restriction, or exercise.

    Let’s dive deeper into the role of NAD+ in our bodies, its decline with age and health issues, and the challenges of oral supplementation.

    Role of NAD+ in the body:
    NAD+ is a crucial molecule that acts as a cofactor and substrate for various cellular processes, including:

    1. DNA repair: NAD+ is essential for repairing damaged DNA, which helps maintain the stability of our genetic information.
    2. Epigenetic regulation: NAD+ plays a role in controlling the expression of genes by modifying their structure. This process is crucial for normal development and cellular function.
    3. Energy production: NAD+ is a key player in the process of oxidative phosphorylation, which generates ATP (the energy currency of our cells).
    4. Intracellular calcium signaling: NAD+ helps regulate calcium levels within our cells, which is important for cellular communication and function.
    5. Immune function: NAD+ is involved in the activation of immune cells, which helps our bodies fight off infections.

    Decline of NAD+ with age and health issues:
    As we age, our NAD+ levels tend to decrease, which can contribute to various age-related issues. Low NAD+ levels have been linked to:

    1. Aging: Reduced NAD+ levels may play a role in the aging process itself.
    2. Cellular senescence: Senescent cells, which are cells that have stopped dividing and are no longer functional, accumulate with age and contribute to tissue dysfunction. Low NAD+ levels may promote cellular senescence.
    3. Inflammation: Decreased NAD+ levels can lead to chronic inflammation, which is a major contributor to various age-related diseases.
    4. Metabolic dysfunction: Low NAD+ levels have been implicated in insulin resistance, type 2 diabetes, and other metabolic disorders.

    Challenges of oral NAD+ supplementation:
    Despite the potential benefits of boosting NAD+ levels, taking NAD+ orally is not a straightforward solution. This is because:

    1. Poor bioavailability: Oral NAD+ supplementation has poor bioavailability, meaning that only a small fraction of the ingested NAD+ is absorbed into the bloodstream.
    2. Gut metabolism: NAD+ is metabolized by enzymes in the gut, which further reduces its availability to the body.
    3. Inefficient conversion: When NAD+ is absorbed, it may be converted back to its inactive form, NAM, by the enzyme NADase.

    Alternative NAD+ precursors:
    Researchers are exploring alternative precursors of NAD+ that might be more effective in boosting NAD+ levels. These precursors include:

    1. Nicotinic acid (NA): NA is a direct precursor of NAD+ and has been shown to increase NAD+ levels in certain tissues.
    2. Nicotinamide riboside (NR): NR is a precursor of NAD+ that is more stable than NAD+ itself and has been shown to increase NAD+ levels in mice.
    3. Nicotinamide mononucleotide (NMN): NMN is another precursor of NAD+ that has been shown to increase NAD+ levels in mice and is currently being studied for its potential benefits in humans.
    4. Nicotinamide adenine dinucleotide ribose (NAR): NAR is a form of NAD+ that contains ribose instead of deoxyribose. It has been shown to increase NAD+ levels in certain tissues.

    These alternative precursors are being investigated for their potential to improve NAD+ levels and provide therapeutic benefits. However, more research is needed to understand their efficacy and safety in humans fully. Intravenous infusion of NAD+ remains the most effective way to boost NAD+ levels, but alternative precursors may offer a more convenient and effective option.

    The discovery of Sirtuins, a group of enzymes that depend on NAD and are linked to longevity, has opened up a new frontier in aging research. Recently, there has been a surge of interest in using the NAD/Sirtuin pathway to combat brain aging, and therapies based on this principle are expected to become available in the future.

    A breakthrough in this field is the identification of nicotinamide riboside (NR) as a vitamin precursor of NAD with excellent oral bioavailability in both mice and humans. Studies have shown that a single daily dose of NR (1000 mg) can increase blood NAD+ levels by 270% within seven days. Additionally, NMN, another NAD+ precursor, is metabolized into NR, which is then converted into NAD+ inside cells.

    In mice with metabolic impairments, NR supplementation has been linked to increased SIRT1 expression, reduced oxidative stress, and enhanced mitochondrial function. In a fly model of Parkinson’s disease, NR supplementation has been shown to reduce the loss of dopaminergic neurons and improve motor skills. Furthermore, NR supplementation has been found to reduce tau phosphorylation and enhance cognitive function in a mouse model of Alzheimer’s disease with DNA repair defects.

    Another study demonstrated that NMN supplementation promoted mitogenesis in nematode neurons and improved cognitive decline caused by Alzheimer’s disease. In a rat model of Alzheimer’s disease, NMN reduced Aβ aggregation, enhanced spatial memory, and increased neuronal survival, partly by reducing reactive oxygen species (ROS). These findings suggest that NAD+ precursors like NR and NMN may hold promise in treating age-related brain diseases and improving cognitive function.

  • Spermidine May Increase Human Healthspan

    Spermidine is a polyamine that’s found in various human tissues, and its levels decrease as we age. It’s also abundant in sperm, which helps keep germ cells healthy and alive for a long time. Spermidine levels are influenced by our diet, gut bacteria, and our body’s own production and breakdown processes.

    You can find high levels of spermidine in foods like fresh peppers, wheat germ, broccoli, cauliflower, and cheese. Soy products like natto, shiitake, and durian also have high amounts of spermidine.

    Spermidine has been shown to have many benefits in animal studies. It can help protect the heart and brain and even fight cancer. It’s also been linked to a reduced risk of cancer and heart disease in human studies.

    Spermidine works by maintaining the health of our mitochondria, reducing inflammation, and helping stem cells stay healthy. It also helps by mimicking the effects of calorie restriction, which is when you eat fewer calories but still get all the nutrients your body needs.

    In animal studies, giving spermidine has been shown to increase the survival rate, improve memory, and even help with motor skills. In human studies, taking spermidine supplements is safe and effective in improving memory and reducing blood pressure.

    Here are some of the key details about spermidine and its benefits:

    1. Anti-aging effects: Spermidine has been shown to slow down the aging process by promoting autophagy, a process where cells clean up and recycle damaged components. This helps maintain cellular health and prevent age-related diseases.
    2. Cardioprotective effects: Spermidine has been found to protect the heart by reducing inflammation, oxidative stress, and blood pressure. It may also help prevent cardiovascular diseases like atherosclerosis and heart failure.
    3. Neuroprotective effects: Spermidine has been shown to improve memory, learning, and cognitive function in both animal and human studies. It may also help protect the brain from neurodegenerative diseases like Alzheimer’s and Parkinson’s.
    4. Anti-cancer effects: Spermidine has been found to inhibit cancer cell growth and promote cancer cell death. It may also help prevent cancer by reducing inflammation and oxidative stress.
    5. Mitochondrial health: Spermidine helps maintain the health of mitochondria, the energy-producing structures within cells. This is important for overall cellular health and may help prevent diseases like diabetes and neurodegenerative disorders.
    6. Caloric restriction mimic: Spermidine has been found to mimic the effects of caloric restriction, which is when you eat fewer calories but still get all the nutrients your body needs. This has been shown to have many health benefits, including increased lifespan.
    7. Safety and efficacy: Spermidine has been shown to be safe and well-tolerated in human studies, with no significant side effects. It has also been found to be effective in improving various health markers, such as blood pressure, memory, and cognitive function.

    In terms of dietary sources, spermidine is found in a variety of foods, including:

    • Fresh peppers
    • Wheat germ
    • Broccoli
    • Cauliflower
    • Cheese
    • Soy products like natto, shiitake, and durian

    It’s also available as a dietary supplement, which can be a convenient way to increase your spermidine intake if you’re having trouble getting enough from your diet alone.

    Overall, spermidine is a promising nutrient that has been shown to have many health benefits. Further research is needed to fully understand its effects, but current evidence suggests that it may be a valuable addition to a healthy Longevity Lifestyle.

  • Intermittent Fasting – The Impact on Autophagy, Inflammasome, and Senescence

    A recent study published in Human Nutrition & Metabolism explored the molecular effects of prolonged intermittent fasting on human health and longevity markers. The research revealed that fasting can alter the expression of genes linked to autophagy, the inflammasome, and senescence, which are all related to aging and age-related diseases.

    The study recruited 25 healthy young men who intended to fast for the entire month of Ramadan from dawn to dusk. The researchers measured gene expression levels one week before Ramadan, in the middle of Ramadan, in the last days of Ramadan, and one week after Ramadan.

    The study found that intermittent fasting activated autophagy, a cellular process that breaks down components within cells. Autophagy has been linked to longevity, and the researchers observed an increase in ULK1, a gene involved in autophagy, two weeks and one month after starting the fasting period. Another gene, ATG5, involved in autophagy induction, also showed a similar pattern. However, BECN1, a gene essential for autophagy, exhibited a different pattern, with an increase in expression two weeks after the start of fasting and a subsequent reduction in its levels.

    The researchers also measured inflammation and senescence markers, including the inflammasome and senescence mediator p16INK4a. They found that NLRP3 and IL-1β expression increased two weeks and one month after the start of fasting, but ASC levels were lower than basal levels one month after the start of fasting, suggesting that the inflammasome was not activated. The senescence marker p16INK4a did not show statistically significant changes until the end of the observation period, but p21 levels decreased during and after fasting.

    The study’s limitations include a lack of data on food intake, physical activity, and sleeping patterns, which could impact gene expression patterns. Additionally, only young males were included in the study, making the results questionable for other demographic groups. The authors emphasize the need for further research to confirm or refute their findings and to assess the levels of actual proteins rather than just gene expression levels.

    Overall, the study provides valuable insights into the molecular effects of prolonged intermittent fasting on human health and longevity markers. While more research is needed to understand the complex interplay between autophagy, the inflammasome, and senescence, the findings suggest that fasting may contribute to delaying the onset of age-related diseases and promoting overall health and longevity.