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

Various NAD boosters, drugs, and supplements have been studied for their potential to extend lifespan and improve health, and should be taken with caution and under the guidance of a doctor

Questions to inspire discussion 

• What should I do before making any changes to my diet or supplements?

  —It is important to talk to a physician before making any changes to your diet or supplements.

• Are OTC supplements safe to take?

  —OTC supplements are generally recognized as safe, but it is important to consult with a doctor before taking any supplements.

• What are some popular NAD boosters and supplements?

  —Some popular NAD boosters and supplements include Metformin, berberine, rapamycin, spermidine, resveratrol, fisetin, and quercetin.

• Can NR and NMN raise NAD levels?

  —Yes, both NR and NMN have been shown to raise NAD levels in blood tests.

• What are the potential effects of NMN in humans?

  —NMN has shown potential to increase energy, improve mitochondrial function, blood flow, endurance, insulin sensitivity, and organ protection in humans. 

Key Insights

Longevity Molecules

• 💊 "Today is to talk about some of the major supplements and medicines that are thought and have the greatest scientific evidence to be able to give you wellness now as well as long-term health in the future."
• 💊 Supplementing with molecules like NR or NMN might have long-term health benefits in humans, including improvements in athleticism, less inflammation, and potentially staving off type two diabetes.
• 💊 NMN has been shown to have no negative side effects in human studies and may have similar effects to NR in lengthening lifespan, restoring mitochondrial activity, and enhancing insulin sensitivity.
• 💊 The idea that simply swallowing NR or NMN capsules can raise NAD levels by two to three fold is intriguing and could have significant implications for longevity research.
• 🐭 Fisetin has been shown to extend lifespan in mice by up to 30% and improve health by removing senescent cells and activating Sirt-1 defenses.
• 💊 Taking one gram of NMN every morning can double NAD levels, which is important for aging individuals who have half the levels of NAD than they did when they were 20.

Benefits of Metformin

• 💊 "Metformin is probably the most studied drug in the world for aging."
• 💊 Metformin is a drug that has been used for over 60 years to treat diabetes, but it also has potential as a longevity molecule due to its ability to activate AMPK and increase NAD+ levels.
• 💊 Metformin has been shown to not only extend lifespan in animals, but also lower the risk of diseases such as cancer, heart disease, Alzheimer's, and frailty in humans.
• 💊 The Metformin study aims to show the American FDA that aging can be targeted with a drug and slowed down, potentially making aging a treatable medical condition.

Natural Pathways to Longevity

• 💰 Dr. Sinclair discloses all of his work and potential conflicts of interest, and has actively avoided selling supplements to maintain unbiased discussions on longevity.
• 🏋️‍♀️ Exercise and fasting turn on survival pathways, but if you're low on immuno acids, it'll turn on the mTOR protection pathway, which will then tell the other survival pathways to do their thing too, like the Pentagon coordinating defenses.
• 🧬 The goal of finding safe, natural molecules that activate proteins, not genes, is to extend lifespan without genetically modifying ourselves.
• 🌿 Metformin is a remarkable molecule that comes from the plant world and has multiple pathways of impact, including raising NAD levels and activating sirtuins.

#Health #Wellness

Clips

 00:00 🧐 We discussed ways to combat aging through mimicking evolutionary stresses and popular and promising NAD boosters, drugs, and supplements.

• • We discuss the science of aging and how to live longer and better, while cautioning to talk to a physician before making any changes to diet or supplements.
  • Monitor your blood glucose with Levels to see how different foods impact you and get personalized nutrition recommendations from Inside Tracker and immune support from Athletic Greens.
  • We discussed ways to combat aging through mimicking evolutionary stresses, and discussed the differences between drugs and supplements to give us wellness and long-term health.
  • OTC supplements are generally recognized as safe, but drugs are regulated by the government because they are not in the food supply and could potentially cause damage.
  • Today we're discussing popular and promising NAD boosters, Metformin, berberine, rapamycin, spermidine, resveratrol, fisetin and quercetin, and providing scientific references and disclosures.
  • People use my face on packages without my permission, so let's discuss the three longevity pathways and genes.
• 10:00 🧪 NR is a safe supplement that activates the sirtuin pathway, mimicking caloric restriction, and has been shown to improve health and metabolism in rodents and humans.
  • Different drugs and supplements interact with the three survival pathways, Sirtuins, AMPK, and mTOR, to create a network of responses to environmental changes.
  • NAD is an important molecule for energy production and fighting off aging, and NAD boosters can help restore levels of NAD to those of younger years.
  • NR is a safe supplement with no apparent negative side effects, and it can raise NAD levels in blood tests.
  • NR activates the sirtuin pathway, mimicking caloric restriction, and can extend yeast lifespan by up to 30%.
  • NR supplementation has been shown to improve health and metabolism in rodents, with some positive results in humans.
  • NR is not as effective as NMN in raising NAD levels, likely due to needing other components such as a phosphate to become active.
• 19:23 🤔 NMN has been tested in humans with no negative side effects, and has been shown to increase lifespan in mice by 10-15%, with potential to protect organs and increase wound healing in humans.
  • Studies have shown that NR can raise NAD levels and lower inflammation, but more research is needed to determine its long-term effects.
  • NMN is more effective than NR in animal studies, and is taken up by cells via the SLC128A transporter.
  • NMN has been shown to increase lifespan in mice by 10-15%, with more pronounced effects in females.
  • NMN has been tested in humans with no negative side effects, and results are expected by 2022 to show if it has similar effects to mice, such as increased energy, mitochondrial function, blood flow, and endurance.
  • NMN has been shown to improve insulin sensitivity and may have potential to protect organs and increase wound healing in humans.
  • Others are giving NAD directly through long drips in Florida and LA, but not in a study setting.
• 29:53 🤔 Taking NAD boosters may raise NAD levels, but there is a risk of stimulating cancer growth, while resveratrol from red wine or Polygonum cuspidatum can activate Sirt-1.
  • NAD IVs may help with addiction, depression, and hangovers, but more research is needed to confirm their effectiveness.
  • Swallowing NR and NMN capsules is enough to raise NAD levels by two to three fold.
  • Swallowing NAD boosters has been proven to raise NAD levels, but there is some concern that it may stimulate cancer growth.
  • NMN may increase the number of senescent cells and precancerous/cancerous growths in mice predisposed to pancreatic cancer, possibly due to down-regulating the tumor suppressor gene P53.
  • Resveratrol was found to be the best natural molecule to activate Sirt-1, an enzyme that controls other proteins, in a 2003 Nature study.
  • You can't drink enough red wine to get the beneficial effects of resveratrol, but it can be purified from grapevines or Polygonum cuspidatum.
• 38:22 💊 Resveratrol, fisetin, quercetin, rapamycin, rapalogs, spermidine, and metformin have all been studied for their potential to extend lifespan and improve health.
  • Resveratrol needs to be taken with food to be effective, and has been studied in animals for almost 20 years, showing extended replicative lifespan in yeast.
  • Resveratrol, fisetin, and quercetin have been shown to reduce fasting glucose, increase insulin sensitivity, lower cholesterol levels, and protect against cancer in both animal and human studies.
  • Fisetin and quercetin have been shown to extend lifespan and improve health by killing senescent cells and activating Sirt-1 defenses, with quercetin being more extensively studied and dasatinib being a regulated drug used to treat leukemia.
  • Fisetin is the most accessible senolytic for people, but rapamycin and rapalogs have been shown to extend lifespan in many organisms and may be useful in humans, though they are not currently available.
  • Rapamycin and spermidine both extend lifespan in animals and have been shown to improve memory in humans.
  • Metformin, an AMPK activator, has been used since the 1950s to treat type two diabetes and is relatively safe, available over the counter in some countries and by prescription in others.
• 52:23 💊 Metformin and Berberine are low-cost molecules that have been found to mimic the effects of Metformin, impacting multiple pathways and potentially providing health benefits, but with potential side effects.
  • Metformin, a simple molecule from the plant world, lowers energy, inhibits mTOR, activates AMPK, and raises NAD levels, impacting multiple pathways.
  • Metformin has been found to extend lifespan in animals, lower glucose levels, increase energy, reduce inflammation, and reduce the risk of other diseases in humans.
  • Metformin is being studied to target aging, but it is difficult to raise money for the study due to its low cost and lack of profit motive, and doctors are increasingly prescribing it off-label to pre-diabetic patients.
  • Metformin does not have a significant effect on muscle size, but may reduce inflammation and strength on days taken, and berberine is an alternative that works on similar pathways.
  • Berberine, a yellow substance found in bark and roots, has been found to mimic the effects of Metformin, increasing sensitivity to insulin and lowering blood glucose levels, with potential health benefits, but may have similar side effects to Metformin.
  • To calculate the dosage of resveratrol for humans, use allometric scaling, which is 12 times the dosage given to a mouse.
• 01:03:57 💊 Take 1 gram of resveratrol, NMN, fisetin, quercetin, spermidine, and 800mg of Metformin daily, but consult a doctor first.
  • Take 1 gram of resveratrol daily in the morning with NMN, which can be dissolved in water or taken sublingually.
  • Taking 1 gram of NMN daily can double NAD levels, while taking 2 grams can triple them, and taking it in the morning can help reset the body's clock.
  • I take 800mg of NMN and Metformin at night with dinner to simulate a fast and improve my blood biochemistry, but pause Metformin on days before exercise.
  • Take 1 gram of resveratrol with yogurt or olive oil, 1 gram of NMN, half a gram of fisetin and quercetin with yogurt, 1 gram of spermidine in the morning, and 800 milligrams of Metformin in the evenings.
  • People should consult their doctor before taking drugs or supplements and monitor their liver to ensure they are doing no harm.
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