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David Sinclair: Longevity Molecules

Updated: Jan 15

Release Date: 1/26/2022

Podcast Duration: 1:10:30

A Summary by Brandon Johnson, DC

3 Key Takeaways

  1. Antioxidants can be taken to kill senescent cells (dysfunctional cells that create inflammation and increase cancer risk)

  2. Increasing NAD is directly correlated with anti-aging properties

  3. Increasing insulin sensitivity and improving the bodies ability to make energy, seems to be the two most crucial factors in slowing down the aging process

Dr. Sinclair begins this podcast by talking about different drugs and supplements that are showing promise in regards to optimizing human health and reducing age related issues.

NAD (Nicotinamide Adenine Dinucleotide)

  1. Why is NAD important?

  2. Our cells use NAD to transport hydrogen atoms

  3. Helps us make energy

  4. Activates “sirtuins” defensive enzymes that protect the body

  5. As we age our body produces less NAD and destroys more in the body

  6. Exercise helps boost naturally

NR (Nicotinamide Riboside)

  1. Has been taken since 2014

  2. Shows little to no side effects in human trials

  3. Will raise NAD levels

  4. Yeast lived 30% longer when given NR

  5. 250mg-1g of NR will raise NAD levels

  6. Lowers inflammation in people

NR Pathway

  1. Enters blood stream

  2. Absorbed into muscle and brain

  3. Then forms NMN

  4. 2 NMN bind together to form NAD

After explaining NAD and supplements that increase levels, Dr. Sinclair talks about the most bio-available (effective) way to raise levels in the form of NMN.

NMN (Nicotinamide Mononucleotide) - more research needs to be done in humans but several studies have yeilded great evidence in mice

  1. Increases oxidative metabolism

  2. Makes them thinner

  3. Reduces diabetic effects

  4. Mice lived longer 10-15%

  5. Better insulin sensitivity

  6. Restoring mitochondria (the system that makes energy in the cell)

  7. Increased endurance

  8. Protects organs

  9. No big differences in bio-availability when injected, swallowed or sublingual

Why don't we just take NAD?

  1. NAD might be too big to be transported or reabsorbed into cells

  2. Studies have shown that taking NAD does not result in increase in blood levels

After talking about NAD and how it applies to human health, Dr. Sinclair discusses other supplements that have antioxidative properties and activates sirtuins.


  1. Activates sirtuins

  2. Found in red wine

  3. Need hundreds of glasses per day to get a good dose

  4. Will dissolve in oil or fats

  5. 250mg-1000mg per day

  6. Obese mice taking resveratrol lived as long as thin ones

  7. In humans

  8. Lowers bad cholesterol

  9. Raise HDL good cholesterol

  10. May reduce cancer risk

Fisetin & Quercetin

  1. kill senescent cells (dysfunctional cells that create inflammation and increase cancer risk)

  2. Act as powerful antioxidants


  1. Used since 1950

  2. Activates ampk (helps the cell to make energy)

  3. Make more mitochondria

  4. Inhibits mtor improves insulin signaling

  5. Raises NAD levels

  6. Less inflammation

  7. Reduces muscle switching

  8. Old muscles switch to anaerobic pathways do not use oxygen as effectivley

  9. Commonly prescribed off label (for reasons other than what is intended by the manufacturer)

  10. May reduce muscle growth

  11. May make you feel fatigued

  12. Can irritate stomach

  13. Berberine- mimicks metformin

  14. Naturally occurring

  15. 1-2 grams daily

  16. Fewer side effects

Drugs that inhibit mtor (activated in cancer cells) mimicking fasting

  1. Rapamyacin -not readily available or prescribed

  2. Spermadine-stimulates autophagy (clearing of bad cells)

What is David Sinclair's Routine

  1. Morning

  2. Takes Resveratrol-1gram daily since 2004

  3. Must add fat to it-mixes with olive oil or yogurt

  4. Takes NMN- 1gram

  5. Takes NMN in the morning because that is when NAD levels should rise

  6. Fisetin and Quercetin

  7. Evening

  8. 800mg metformin

  9. Spermadine

  10. Just started testing on himself 1 gram daily

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