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NMN, NR, Resveratrol, Metformin & Other Longevity Molecules | Lifespan with Dr. David Sinclair #4

David Sinclair・64 minutes read

Lifespan podcast hosted by David Sinclair and Matthew LaPlante delves into aging science and discusses ways to slow, stop, and reverse aging, focusing on popular supplements like NR, NMN, and Metformin to enhance longevity pathways and combat aging. Various supplements and drugs like resveratrol, rapamycin, spermidine, and berberine are explored for their potential benefits in extending lifespan, improving metabolic health, and reducing the risks of age-related diseases in humans and animals.

Insights

  • NAD, a crucial molecule for energy production and cellular processes, decreases with age, impacting the body's ability to combat aging and diseases.
  • NMN, a potent NAD booster, shows promising results in enhancing mitochondrial function, improving insulin sensitivity, and extending lifespan in animal studies, with ongoing human trials at Harvard Medical School.
  • Resveratrol, a compound found in red wine, demonstrates various health benefits, including increased insulin sensitivity, reduced fasting glucose, and potential cancer suppression, with recommended daily intake for efficacy.

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Recent questions

  • What is the role of NAD in the body?

    NAD, or nicotinamide adenine dinucleotide, is a crucial molecule for transferring hydrogen atoms in cells, essential for energy production and activating defensive enzymes called sirtuins. As the body ages, NAD levels decrease, impacting the body's ability to combat aging and diseases. Popular NAD boosters like NR and NMN help replenish NAD levels, improving mitochondrial function, reducing inflammation, and potentially extending lifespan.

  • How do NMN and NR impact NAD levels?

    NMN and NR are popular NAD boosters that play a significant role in raising NAD levels in the body. NR, or nicotinamide riboside, is converted to NMN, then to NAD, mimicking caloric restriction and enhancing genome stability. NMN, considered more effective than NR, potentially due to the presence of phosphate, enhances insulin sensitivity, restores NAD levels, and improves mitochondrial function. Studies have shown that both NMN and NR can increase NAD levels, lower inflammation, and have positive effects on body composition.

  • What are the potential benefits of resveratrol?

    Resveratrol, found in red wine but not recommended in large quantities for its benefits, has shown various positive effects in animal and human studies. It has been linked to increased metabolic rate, protection against free radicals, improved insulin sensitivity, and reduced fasting glucose levels. Resveratrol has also demonstrated effects on body composition, metabolic rate, glucose levels, and cardiovascular health. When taken in daily doses of 250-2000 milligrams, preferably mixed with food, resveratrol can potentially mimic caloric restriction and offer various health benefits.

  • How does Metformin impact aging and health?

    Metformin, widely used for diabetes, is an AMPK activator that improves energy production and insulin signaling by activating complex one. It has shown benefits in lowering glucose levels, increasing energy, reducing inflammation, and improving muscle type switching in animals and humans. Metformin has been associated with lower risks of diseases like cancer, heart disease, Alzheimer's, and frailty in elderly individuals. Despite potential side effects like lactic acidosis and muscle loss, doctors are increasingly prescribing Metformin off-label for its potential anti-aging benefits.

  • What are the potential effects of rapamycin on lifespan?

    Rapamycin and rapalogs, which inhibit mTOR and mimic fasting, have shown potential for extending lifespan in various organisms. Animals given rapamycin mimic low protein intake, inducing autophagy to recycle old proteins. Giving rapamycin late in life has been shown to extend lifespan, although it could be toxic and is currently unavailable for human use. Low doses of rapamycin are considered for potential lifespan extension, with ongoing research into its effects on aging and health.

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Summary

00:00

"Longevity Science and Health Tips Podcast"

  • Lifespan podcast hosted by David Sinclair and Matthew LaPlante discusses aging science and health tips.
  • David Sinclair, a Harvard Medical School professor, and Matthew LaPlante co-host the podcast.
  • The podcast delves into ways to slow, stop, and reverse aging.
  • Audience requests for supplement advice prompted a deep dive into supplements like NR, NMN, and Metformin.
  • Research team spent weeks compiling notes on supplements to separate fact from fiction.
  • Disclaimer: David and Matthew are not medical doctors, advise consulting a physician before making significant dietary or supplement changes.
  • Sponsors of the podcast include Levels, Inside Tracker, and Athletic Greens, offering tools for health monitoring and improvement.
  • The episode focuses on discussing popular and promising supplements and drugs like NAD boosters, Metformin, berberine, rapamycin, spermidine, resveratrol, fisetin, and quercetin.
  • Supplements and drugs are categorized based on their impact on longevity pathways like sirtuins, AMPK, and mTOR, which interact and influence each other in the body.

11:52

"Unlocking NAD: Vital for Energy and Aging"

  • NAD was discovered by Germans in yeast extracts about 100 years ago, essential for chemical reactions.
  • NAD stands for nicotinamide and adenine dinucleotide, crucial for transferring hydrogen atoms in cells.
  • NAD is abundant in the body, vital for energy production and activating defensive enzymes called sirtuins.
  • Aging leads to decreased NAD levels, impacting the body's ability to combat aging and diseases.
  • Supplements like NR, nicotinamide riboside, are popular NAD boosters, safe with no apparent side effects.
  • NR extends lifespan in yeast and mice, mimicking caloric restriction and enhancing genome stability.
  • NR is converted to NMN, then to NAD in the body, improving mitochondrial function and reducing inflammation.
  • Human studies on NR show increased NAD levels, lower inflammation, and minor body composition changes.
  • NMN is considered more effective than NR in raising NAD levels, potentially due to the presence of phosphate.
  • NMN enhances insulin sensitivity, restores NAD levels, and improves mitochondrial function in animal studies.

24:23

"NMN: Benefits, Dosage, and Potential Risks"

  • NMN was initially rare but is now available for purchase.
  • Studies conducted in a lab show that mice treated with NMN exhibit reduced frailty, improved activity, better mitochondrial function, and increased lifespan.
  • The dosage used in the studies is 400mgs per kg.
  • The lifespan extension with NMN is around 10 to 15%, more pronounced in females.
  • Human studies on NMN are ongoing at Harvard Medical School, with no negative side effects reported so far.
  • NMN has shown positive effects in humans, such as improved insulin sensitivity and glucose disposal.
  • NMN may protect organs and enhance wound healing in humans.
  • NAD IV drips are being used by individuals for various purposes, including addiction treatment, depression, and hangovers.
  • NMN is a smaller molecule than NAD, making it more bioavailable and effective in raising NAD levels.
  • Concerns about NMN potentially stimulating cancer growth have been raised, with conflicting results from studies in mice.

36:21

Resveratrol: Red Wine Molecule with Benefits

  • In the early 2000s at Harvard, the goal was to find a safe molecule to activate a specific protein, Sirt-1, not the gene, through an enzyme that controls other proteins.
  • An essay was set up to test Sirt-1 activation, leading to the discovery of resveratrol as the best activator, found in red wine.
  • Drinking red wine in large quantities is not recommended for resveratrol benefits; instead, it can be purified from grapevines or polygonum cuspidatum.
  • Human studies suggest a daily intake of 250-2000 milligrams of resveratrol for efficacy, preferably mixed with food due to its hydrophobic nature.
  • Resveratrol has shown various benefits in animal studies, including metabolic rate increase, protection against free radicals, and mimicking caloric restriction.
  • Human studies on resveratrol have demonstrated reduced fasting glucose, increased insulin sensitivity, and improved cholesterol levels.
  • Resveratrol has been known to suppress cancer and has shown effects on body composition, metabolic rate, glucose levels, and cardiovascular health.
  • Fisetin and quercetin, like resveratrol, are potential senolytics, removing senescent cells and extending lifespan in model organisms.
  • Quercetin, combined with dasatinib, has shown remarkable effects in treating age-related diseases, reducing liver steatosis and inflammation.
  • Rapamycin and rapalogs, inhibiting mTOR and mimicking fasting, have shown potential for extending lifespan in various organisms, with low doses considered for human use.

48:31

"Metformin and Spermidine: Anti-Aging Potential Revealed"

  • Giving rapamycin late in life extends lifespan, but it could be toxic and is currently unavailable.
  • Rapamycin inhibits mTOR, which stands for Target Of Rapamycin.
  • Animals given rapamycin mimic low protein intake, inducing autophagy to recycle old proteins.
  • Spermidine, working on autophagy, extends lifespan in yeast, flies, worms, and mice.
  • Spermidine stimulates autophagy and stabilizes epigenome changes, potentially combating aging.
  • Spermidine can be obtained from wheat germ and soy products.
  • Metformin, an AMPK activator, is widely used for diabetes and activates complex one to improve energy production and insulin signaling.
  • Metformin has shown benefits in glucose lowering, energy increase, inflammation reduction, and muscle type switching in animals and humans.
  • Metformin has been linked to lower risks of diseases like cancer, heart disease, Alzheimer's, and frailty in elderly individuals.
  • Doctors are increasingly prescribing Metformin off-label for potential anti-aging benefits, despite potential side effects like lactic acidosis and muscle loss.

01:00:47

"Berberine Mimics Metformin Effects, Enhances Health"

  • Berberine, a molecule from plant bark and roots, mimics Metformin effects by binding to complex one, reducing chemical energy, amplifying mitochondria, increasing insulin sensitivity, and lowering blood glucose.
  • Berberine doses of one to two grams per day have shown positive effects in mice and humans, extending lifespan and improving insulin sensitivity.
  • Berberine has similar side effects to Metformin, including diarrhea, constipation, gas, and upset stomach.
  • Resveratrol, taken in a gram dose daily since 2004, should be consumed with fat like yogurt or olive oil to enhance absorption.
  • NMN, taken in a gram dose daily, dissolves easily and can be taken in the morning without food.
  • Metformin, taken at 800 milligrams at night, simulates fasting benefits and is added to the regimen for improved health.
  • Spermidine, taken in a gram dose daily, is a recent addition to the regimen, with ongoing monitoring of its effects.
  • Fisetin and quercetin, taken in half a gram doses daily, target senescent cells and are part of a maintenance regimen.
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