Why We Age and Why We Don’t Have To (NAD+, NR, NMN, Sirtuins, Xenohormesis, and More) – Dr. David Sinclair on Ben Greenfield Fitness

Check out the Ben Greenfield Fitness Episode Page & Show Notes

For the most comprehensive take on all of David Sinclair’s recommendations and the best ideas on optimizing healthspan, check out The 5 Pillars to Optimize for Increasing Healthspan and Living Your Best Life

Key Takeaways

  • The theory of aging: It’s not the DNA that deteriorates as we get older, but the ability to read the genetic code within the DNA
    • A good analogy for aging: DNA is like a DVD; the older you get, the more scratches the DVD develops and the harder it becomes for the DVD player to read it
  • Sirtuins are a class of proteins that protect organisms from deterioration and disease by regulating gene expression (turning genes on/off)
    • Sirtuins need NAD+ to function properly
  • NR and NMN are NAD+ precursors you can supplement with – both have been shown to raise NAD+ levels
    • You can also raise NAD+ levels with fasting and exercise 
  • Longevity is only ~20% genetic, the rest is up to us
  • Resveratrol, and other beneficial plant molecules, known as xenohormetics, are produced in plants under stress
    • By eating stressed plants, we obtain these useful molecules and activate our own stress response pathways (helping us fight aging)

Products Mentioned

  • The two best NAD+ precursors:
    • NR
      • For us at Podcast Notes, based on their unmatched quality standards and our personal experience, we strongly recommend Elysium Basis (use the code “podcast45” at checkout to receive $45 off a semi/annual subscription)
    • NMN
      • David supplements with 1 gram of capsulized NMN every morning (he doesn’t disclose his preferred brand)

Intro

  • David Sinclair (@davidasinclair) is a Professor in the Department of Genetics at Harvard Medical School
    • Find all of our Podcast Notes with David Sinclair here
  • Host – Ben Greenfield (@bengreenfield)

Books Mentioned

A Day in the Life of David Sinclair

  • David has one mission in mind: “Leave the world a better place than I found it”
  • David spends a lot of his time in the lab or teaching students at Harvard
  • Additionally, David gives lectures around the world and serves as an advisor to multiple companies
    • “I’m an entrepreneur and I keep myself busy… I try not to waste a second of my life” – David Sinclair

What Causes Aging?

  • 🎧 The theory of aging: It’s not the DNA that deteriorates as we get older, but the ability to read the genetic code within the DNA
    • A good analogy for aging: DNA is like a DVD; the older you get, the more scratches the DVD develops and the harder it becomes for the DVD player to read it
  • “Essentially, what I’m saying in my book is that aging occurs due to a loss of information over time, and you can accelerate that loss by cutting DNA (damaging it). But it’s not the DNA itself that’s the problem, it’s the packaging of the DNA that tells which genes to read at what time.” – David Sinclair
    • “Much like if you unwrap a present, you can re-gift it a few times by rewrapping it. But, if you try to do that thousands of times, it’s going to look really messy.” 

Is it Possible to Reverse Aging?

  • In 2012, a Japanese professor won the Nobel Prize for discovering Yamanaka factors (AKA reprogramming genes)
  • David and his team, using these Yamanaka factors, have been able to repair eyesight in mice
    • (It sounds like these reprogramming factors essentially reverse the age of a cell)
    • How? – They put a set of the reprogramming genes into a benign virus and inject it straight into a mouse’s eyeball (the virus is just a way to get the genes into the cells)
      • The genes are then turned on with an antibiotic 
  • Going further:
    • “It turns out if you take skin cells, or really any adult cell from the body of a person or an animal, you can reprogram them to be really young again. In fact, so young that they become stem cells.” David Sinclair

Living Longer

  • The FOXO3 gene seems to predict some aspects of longevity
  • “Bear in mind that longevity is only 20% genetic and the rest is up to us – how we live our lives. This, to me, tells us that the epigenome, the reading of the genome, is probably more important than the actual variation within our DNA.”  David Sinclair
  • “What we’re learning with longevity is that there’s no one particular daily diet that you should stick to” – David Sinclair
    • “Anyone who says they have an answer and knows 100% what the right thing to do is lying or BS-ing, okay? No one knows exactly the best path to longevity.”
  • David avoids eating too much meat
    • Why? – “If you’re always eating meat… you’ll be switching off your body’s defenses against long-term health. So, that’s why I rarely eat a steak…” – David Sinclair
  • What will help you live longer?
    • Exercise and fasting

NAD+, Sirtuins, NMN, NR, and Metformin

  • Sirtuins are genes which protect all organisms from deterioration and disease
    • They need NAD+ to function
    • “I’m very interested in NAD supplementation to keep the sirtuins active. Sirtuins are part of the epigenome regulators that I think prevent the scratches on the DVD of life.”  – David Sinclair
  • NMN and NR are precursors to NAD+ you can supplement with
    • David takes 1 gram of NMN every morning mixed in with his homemade yogurt, which he’s found to serve remarkably well for maintaining a healthy microbiome
      • A brief aside: “Over 90% of your immune system is in your gut. So, if you’ve restored a gut lining or balanced your gut bacteria, it has a pretty profound impact on the immune system.” – Ben Greenfield
    • When it comes to a brand of NR, we at Podcast Notes can’t recommend Elysium Basis enough (use the code “podcast45” at checkout to receive $45 off a semi/annual subscription). We, Matt and Yoni, have been researching the company and trying Basis out for the past 3 months. Basis is a proprietary formulation of crystalline NR and pterostilbene that supports cellular health by increasing and sustaining NAD+.
  • David also takes metformin
    • ”Many of my colleagues, myself included, think that this is one of the best drugs on the market that you could take for slowing down the process of aging” David Sinclair
    • Although metformin may have an anti-aging effect, some studies show it decreases physical performance in athletes. Because of this, David only takes metformin on days he doesn’t exercise.

Xenohormesis

  • Resveratrol, and other beneficial plant molecules, known as xenohormetics, are produced in plants under stress
    • By eating stressed plants, we obtain these useful molecules and activate our own stress response pathways (helping us fight aging)
  • 🎧 Xenohormesis: “Xeno” means cross-species; “hormesis” is synonymous with a minor stressor that, once recovered from, makes you stronger
    • “We should be seeking out foods that, prior to being picked, were under adversity. So, they’re full of these molecules that we can then ingest and trick our bodies into thinking that times are about to be tough… Ultimately, I think that would lead to healthier and longer life in our bodies as well.” – David Sinclair
  • “If you rip leafy greens up the night before you actually make them into a salad or consume them, you actually can get slightly more of these xenohormetic compounds”- Ben Greenfield
    • Why? – You’re further stressing the plants before eating them

Fewer Sicknesses = Better Health

  • A great measure of your health is how infrequently you get sick
    • “When you look at centenarians, people who live to over 100-years -old, they say that throughout most of their lives, they rarely got sick” – David Sinclair
      • “If you’re one those people who has a bad immune system and always gets sick, that’s probably telling you something about your body and your lifestyle”

Additional Notes

  • Early studies have shown that higher NAD+ levels produce much healthier eggs in female mice
  • “As a good scientist, you’re always trying to prove yourself wrong”  – David Sinclair
  • David takes a cold bath every weekend after spending some time in a warm sauna or hot tub
  • People who go through chemotherapy will be biologically older after the treatment because of the damage done to their DNA
  • KEYTRUDA is an immune-oncology-based cancer drug that is able to target cancer without nuking the body like chemotherapy