Ben Greenfield Interviews Dr. David Sinclair About Lifespan: Why We Age―and Why We Don’t Have To.

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Anti-aging, Body, Diet & Nutrition, Health & Wellness, Podcast, Podcast-new

My guest on today's podcast—Dr. David Sinclair, an acclaimed Harvard Medical School scientist and one of Time’s most influential people—just wrote a paradigm-shifting book.

It’s a seemingly undeniable truth that aging is inevitable. But what if everything we’ve been taught to believe about aging is wrong? What if we could choose our lifespan?

In this groundbreaking new book Lifespan: Why We Age―and Why We Don't Have To, Dr. Sinclair, leading world authority on genetics and longevity, reveals a bold new theory for why we age. As he writes: “Aging is a disease, and that disease is treatable.”

This eye-opening and provocative work takes us to the frontlines of research that is pushing the boundaries on our perceived scientific limitations, revealing incredible breakthroughs—many from Dr. David Sinclair’s own lab at Harvard—that demonstrate how we can slow down, or even reverse, aging. The key is activating newly discovered vitality genes, the descendants of an ancient genetic survival circuit that is both the cause of aging and the key to reversing it. Recent experiments in genetic reprogramming suggest that in the near future we may not just be able to feel younger, but actually become younger.

Through a page-turning narrative, Dr. Sinclair invites you into the process of scientific discovery and reveals the emerging technologies and simple lifestyle changes—such as intermittent fasting, cold exposure, exercising with the right intensity, and eating less meat—that have been shown to help us live younger and healthier for longer. At once a roadmap for taking charge of our own health destiny and a bold new vision for the future of humankind, Lifespan will forever change the way we think about why we age and what we can do about it.

During our discussion in which we take a deep dive into “Lifespan,” you'll discover:

-What does a typical day look like for a scientist at Harvard?…5:45

  • No such thing as a “typical” day
  • Founded and runs several companies
  • Was taught by grandmother and mother to “leave the world a better place than you found it”; this led to his interest in anti-aging and longevity

-Dr. Sinclair's method of speeding up the aging process in mice…8:30

  • Theory on aging: it's not the DNA as much as it is the ability to read the code
  • Epigenome: a record of the chemical changes to the DNA and histone proteins of an organism
  • A broken chromosome is one of the main drivers of the aging process
  • Created a genetically altered mouse with a DNA cutting enzyme (cutting but not mutating)
  • You can look at a person's DNA and tell how old they are biologically
  • Akin to scratching a DVD until it's no longer able to play the movie
  • Aging is the result of cells “forgetting” their identity due to DNA damage
  • The only change was slightly damaged DNA; no stem cells, alterations to telomeres, etc.

-Cellular Reprogramming 101…14:30

  • Yamanaka Factors: genes that turn on in our embryo, and instruct cells what to become
  • First tests done at the Salk Institute in San Diego
  • Mice with cells turned “on” and “off” lived 30-40% longer
  • MiCK gene was left out of mice; this resulted in their tissue becoming younger
  • Genome is akin to a piano: Not fixing the piano, you're fixing the pianist
  • DNA methylation patterns indicate the age of the cells and predict end of life
  • Epigenetic (Horvath's) clock: Much more precise measurements than telomere tests
  • Able to determine the age of previously deceased persons
  • Not commercially available currently

-A device that determines a human genome via a USB connection…23:15

-Whether you can predict your lifespan with your current DNA data from 23andMe…25:15

  • FOXO3 gene
  • Longevity is 20% genetic; the rest is based on our lifestyle
  • Epigenome is more important than the actual DNA
  • Mixed opinions as to the role telomeres play in longevity
  • Tests such as 23andMe are erratic in their accuracy

-The correlation between protein consumption and longevity…29:30

  • Focus on variety in diet vs. one particular “perfect” diet
  • Anyone who says they know exactly what to do is lying
  • Meat contains many branched-chain amino acids (BCAAs); builds muscle
    • Comes at the expense of long-term health
    • mTOR inhibits longevity
  • Plant-based amino acids are preferable
  • Importance of maintaining proper methionine/glycine balance
  • Trimethyl-glycine alleviates discomfort from a NAD IV
  • Nicotinamide adenine dinucleotide (NAD) supplementation keeps sirtuins active (prevents scratching on the DVD)

-The importance of a proper methionine and glycine balance…38:00

-The effects of NMN on fertility…49:15

  • Sirtuin #2 regulates cell division
  • Restore NAD levels in ovaries resulted in healthier embryos in mice
  • Destroy NAD, give NMN, resulted in healthy embryos
  • The field is reluctant to embrace this; no one wants to rewrite the textbooks

-Uncoupling proteins, and whether DMP supplements are a good idea…53:10

  • DMP is extremely toxic; deaths have been reported after use
  • Mitochondria power the cells
    • Similar to hydroelectric dam
    • Circumvent by poking holes in the dam
    • DMP damages mitochondria
  • Overdoses resulted in death
  • Cold thermogenesis is efficacious in uncoupling proteins
  • New drug that's as effective as DMP minus the toxicity is on the horizon – Continuum Biosciences
  • Sirtuin #3 is beneficial for mitochondria

-Resveratrol, stressed wine and fruit, and longevity…58:00

  • Resveratrol slows aging by mimicking calorie restriction; activates sirtuin #1
  • Plants make resveratrol to make their own protective enzymes
  • Stressed plants hit pathways in our body that make us healthier
  • Most drugs we take are derived from stressed plants
  • Xenohormesis: anything that doesn't kill you makes you stronger
  • Book: Eating on the Wild Side by Jo Robinson
  • “Be cruel to your food”

-Cancer breakthroughs in which Dr. Sinclair is currently interested…1:03:15

  • Chemo is designed to damage DNA
  • Repairing DNA accelerates age clock; cancer survivors age tremendously
  • Keytruda – a form of immuno-oncology
    • Has potential to be the world's most profitable drug in coming years
    • Jimmy Carter's life was saved thanks to Keytruda
    • Only known side effect is to restore hair color in men
  • Aging journal Ben and David discuss
  • Dr. Sinclair's website and newsletter

-David's personal protocol…1:10:30

  • Oura ring
  • Inside Tracker (blood tests)
  • Dr. William Davis yogurt recipe
  • The frequency in which you get sick is a great measurement for your longevity
  • NMN supplement
  • Cold thermogenesis
  • Resveratrol (98% purity or higher)
  • Metformin

-And much more…

Click here for the full written transcript of this podcast episode.

Resources from this episode:

Dr. Sinclair's website and newsletter

– Book:  Lifespan: Why We Age―and Why We Don't Have To

Chris Masterjohn Methionine Glycine balance database

Exogenous nicotinamide adenine dinucleotide regulates energy metabolism via hypothalamic Connexin 43 (Roh, 2018)

– Dr. William Davis yogurt recipe

Aging journal

Article on Nature about Steven Horvath's study on the “epigenetic clock”

– Jump Start Fertility

– Book: Eating on the Wild Side by Jo Robinson

Continuum Biosciences

Dry Farm Wines

BGF podcast w/ Todd White of Dry Farm Wines

Episode sponsors:

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Do you have questions, thoughts or feedback for David or me? Leave your comments below and one of us will reply!

Ask Ben a Podcast Question

33 thoughts on “Ben Greenfield Interviews Dr. David Sinclair About Lifespan: Why We Age―and Why We Don’t Have To.

  1. Dale says:

    How can one’s research become the standard? Dr Ken Berry, Dr Paul Saladino would take a different perspective.
    How do we really know which is the proper approach?

  2. Gerard says:

    I think ‘DMP’ should be DNP? (dinitrophenol)

  3. Peter Collins says:

    Dr. Sinclair – I’m about 1/2 way through your book and learning so much. I saw the comment on your blog about resveratrol’s effect on endurance. I’m sure you also saw the study “Resveratrol blunts the positive effects of exercise training on cardiovascular health in aged men”. What do you make of the results and hypothesis in this study? I know you only exercise on the weekends, but if you exercised daily would you stop taking resveratrol all together? Thanks!

  4. Carl Watson says:

    As the next logical bio hack re; vampire transfusions, would “Man who had transplant finds out months later his DNA has changed to that of donor 5,000 miles away” potentially have increased his chances of living longer (assuming the donor was much younger)?

  5. jackie says:

    Found this interview compelling and just read the book. Unfortunately I find little mention of aging due to poor cell communication, as may happen with EMF/RF exposure at night. (That’s why phones go into airport mode and bluetooth and WiFi are off, etc.) Unfortunately he hasn’t heard of Zack Bush, M.D. His stance on the safety of GMO food, although not literally wrong, fails to consider that GMO means “GMO-Round Up Ready” and glyphosate is the scourge of farmland. So, I read it and now it goes in the trash. I can’t pass it on with glaring misinformation about the danger of removing an important constituent of plants to make them tolerate poison.

    1. ace says:


  6. clint moran says:

    Is there an nmn supplement Recomended?

    1. It is good practice to seek ultra-pure, “GMP” grade material. As a scientist, I am unable to recommend products. That said, helpful info’ and science updates are posted every few weeks or so @

  7. Richard Henderson says:

    I think the work Dr Sinclair is doing is amazing and also taking the time to get the information out and putting himself out there is great.

    However I feel that I have to correct something he spoke about and was obviously ignorant about and incorrect which is ok it to hard to keep up with all the information out there.

    It was his comments about Keytruda for cancer he said the only side effect was changing your hair color back to its original state. I am a doctor and have taken care of patients with cancer treated with Keytruda and there have been some miracles with it BUT it can come with some very serious side effects. It can cause severe inflammation in any or multiple organs. I have seen colitis so bad they had diarrhea 20 times a day, pneumonitis, hepatitis, nephritis, encephalitis etc and sometimes nothing cures the side effect and they can die from it.

    So you can read the PI about it to see for yourself.

    So Ben if you could kindly pass this information on to Dr Sinclair so he won’t accidentally misrepresent the total picture of Keytruda when he is giving interviews and talks I would appreciate it and hopefully he will appreciate the heads up as well.

    Appreciate Your podcast

    1. jeremy says:

      My father was diagnosed with stage 4 lung cancer in 2020 – after Keytruda therapy (still going) he is almost fully recovered and the tumor is almost gone!! But yes – side effects were present, but nowhere near as bad as chemo.

  8. Chris Meyer says:

    Dr. Sinclair’s research and outlook seems to be contrary to Keto or Carnivore in many respects. Is there a balance? Such as half meat and healthy fats and half veggies? And how are you changing your diet, if at all, in light of what has been learned from Dr. Sinclair?

    There’s a lot of nutrition and optimization information out there and sometimes it’s hard to strike a balance or find that sweet spot, so to speak, when there’s a lot of conflicting studies.

  9. Antoine says:

    Hi there,

    Thank you for that fantastic interview with David containing a lot of precious insights on aging!

    That said, I am a bit confused regarding the relationship between exercise and longevity. Exercise is definitely good but promotes the mTOR pathway, and David says we want to keep it down as much as possible.

    After a workout session, how long is the mTOR pathway active? If we do sport every day are we counterproductive?

    Taking a meal with proteins from food after exercise is still a good practice?

    Thanks in advance,

  10. Dave says:

    2 comments intended to be helpful

    1. A key concept that may have been confused earlier in the interview is that I believe Sinclair is referring to DNA as both the base pairs and the additional methylation “sign posts” that hang onto the casing of the DNA structure.

    2. From Dr Rhonda Patricks Longevity report. The FOXO3 SNPs that Ben referred to seems to like the T’s instead of C’s

    FOXO3 rs2764264(T;T) May increase lifespan This genotype, rs2764264(T;T), is associated with increased lifespan. Findings from a study that relied on

    case-control and longitudinal data from more than demonstrated that those who had

    achieved greater age (older than 90 years) were more likely to carry one or more of the T alleles (C;T or T;T) of the rs2764264 variant of the FOXO3 gene.

    1. sinfan says:

      you are a clown who pretends science

  11. david says:

    How do you make Dr. William Davis’ yogurt recipe with coconut yogurt?

  12. Ben N. says:

    Would like to hear David Sinclair’s take on fellow NAD coenzyme researcher Charles Brenner, who is a bit critical of supplementing with NAD precursors (NAM/NMN/NA) except for NR (Tru Niagen). Charles also mentions that pterostilbene is a more bio-available form of resveratrol, yet that appears to raise LDL in humans, so he is skeptical about these compounds.

    I’d also love to hear a discussion between evolutionary biologist Michael Rose and David.. Michael suggests it’s hundreds of genes that become maladaptive as you age.. and doesn’t believe the techniques to manipulate some pathway (ex. AMPK/MTOR/NAD via CR mimetics) will work on humans. Incidentally, Steven Austad , Keith Baar and Aubrey de Grey have also expressed reasons why Caloric-Restriction does not have much lifespan effect in humans.

    BTW, looking forward to David’s friendly bet with Geoffrey Woo, that suggests changing gene expression of unhealthy cells, causes it mimic adjacent healthy cells.. while David I believe says that each cell has an original dna ‘observer’ copy that just needs to be activated.

    1. Candice says:

      I did not realize that pterostilbene raised LDL. I should probably stop taking it. Anyone have more info of this?

    2. jackie bee says:

      Others have said about NAD+ … that NR, (including Tru-Niagen brand?) does not make it through digestive process. Sinclair likes NMN and Brenner likes NR, but there are now under tongue and nasal spray forms that mostly by-pass digestion.

      1. jackie says:

        here’s a link:

        They are pricey, but so is Tru-Niagen.

    3. Good questions. I love to debate as much as anyone, but in this case, I think it’s best to do good science and let the data speak. I’d be happy to discuss the topic of aging with Dr. Rose. As for the bet, I’m also going to let the data speak. In my lab, one of my students is doing experiments to test if the reprogramming benefits of OSK on neurons and the presence of the putative “observer” are cell-autonomous or not. Stay tuned.

  13. Billy Davis says:

    Great one. Any experience/thoughts on the CBD/NAD nasal spray offered at Koniver Wellness versus oral/IV?

  14. Matthew S says:

    I may have misheard – butI think Dr Sinclar mentioned that he uses ‘Bravo’ yogurt sachets for his homemade yogurt recipe. Has any one been able to find a link to these?

    1. Dave-o says:

      I believe this is the site:
      1 week’s worth is $48, 4 weeks is $150, 13 weeks is $400, Not cheap, but you do get Bovine colostrum packs to mix in.
      Here is their preparation recipe:
      Seems expensive, but 1 week’s worth is 7 packs of each of the 3 ingredients, and will yield 1 litre of yogurt.
      Plus, you can use the yogurt as a starter for the next batch as suggested in the recipe that Ben linked.
      Ben, can you confirm this?

      1. Matthew S says:

        Thanks for the reply Dave!

  15. Rob says:

    From your notes: Trimethyl glycine (TMG) is also called butane
    Pretty sure that’s a typo lol!
    Should be ‘betaine’, not butane.

  16. Doc Duhame says:

    Hey BG Homies!

    I hit ‘confirm my subscription’ button and it went to an error page…please check that my subscription is still confirmed!


    1. jackie says:

      had same error message

      1. Look for an email from Kion.

    2. You are still on the list! Not sure what happened there, but I'll look into it. Thanks for the heads up.

  17. Diane James says:

    Super podcast with Dr. Sinclair, Have heard Dr. sinclair on other podcasts and your podcast was the best interview of Dr. sinclair that I have heard. Ben, your questions and knowledge really helped me understand the science presented by Dr. Sinclair, thank you. Am ordering his book for further study!

    1. John Teske says:

      Diane James, I definitely second your comment. This was by far the most informative I’ve heard David Sinclair on a podcast. It’s as if the others didn’t know how to get him talking about anything informative, or just barely scratched the surface, but this was great.

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