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Huberman Lab

Essentials: The Biology of Slowing & Reversing Aging | Dr. David Sinclair

30 Oct 2025

38 min duration
7129 words
2 speakers
30 Oct 2025
Description

In this Huberman Lab Essentials episode, my guest is Dr. David Sinclair, PhD, a professor of genetics at Harvard Medical School and a leading expert on the biology of aging. We discuss the cellular and molecular mechanisms of aging—and how specific behaviors, such as fasting, regular exercise and NAD⁺-boosting compounds like NMN, can activate the body's natural longevity pathways. This discussion highlights how lifestyle choices profoundly influence the aging process and may even slow or reverse key aspects of biological aging. Read the episode show notes at hubermanlab.com. Thank you to our sponsors AGZ by AG1: https://drinkagz.com/huberman David: https://davidprotein.com/huberman Eight Sleep: https://eightsleep.com/huberman Timestamps (0:00) David Sinclair (0:20) Longevity, Anti-Aging, Aging as a Disease (2:27) Causes of Aging; Epigenome & Genes (4:53) CD & Scratches Analogy, DNA, Silencing & Expressing Genes (6:44) Physical Appearance & Aging (7:36) Sponsor: David (8:54) Childhood Development & Aging, Horvath Clock, Accelerate Aging (11:30) Rates of Puberty & Aging, Growth Hormone (12:37) Body Size & Longevity; Epigenetics (13:07) Fasting, Calorie Restriction & Longevity, Sirtuins, Insulin & Glucose (16:31) Tool: Skip a Meal (17:07) Longer Fasts & Autophagy, “Deep Cleanse” (18:07) Sponsor: AGZ by AG1 (19:36) Fasting, Fluids, Electrolytes (20:16) Sirtuins, Glucose, mTOR & Fasting; Leucine, Tool: Pulsing Behaviors (24:24) Breaking a Fast, Tools: Do Your Best; Transitions (27:00) Sirtuins, NAD, NMN Supplementation (29:04) Sponsor: Eight Sleep (31:10) Iron & Senescent Cells; Personalize Medicine (32:40) Tool: Blood Markers, CRP (34:50) Tool: Aerobic & Resistance Exercise (35:55) Estrogen, Fasting & Fertility; Aging & Rejuvenation (38:20) Acknowledgements Disclaimer & Disclosures Learn more about your ad choices. Visit megaphone.fm/adchoices

Audio
Transcription

Full Episode

0.031 - 21.303 Andrew Huberman

Welcome to Huberman Lab Essentials, where we revisit past episodes for the most potent and actionable science-based tools for mental health, physical health, and performance. I'm Andrew Huberman, and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine. And now my conversation with Dr. David Sinclair. Thanks for being here.

0

21.623 - 42.847 Andrew Huberman

I have a ton of questions for you about aging, longevity, lifespan, actionable protocols to increase how long we live, et cetera. And I just want to start off with a very simple question. What is aging? the difference between longevity, anti-aging, and aging as a disease. Because I associate you with the statement, aging is a disease.

0

43.529 - 63.64 Dr. David Sinclair

Right. Well, so longevity is the more academic way we describe what we research. Anti-aging is kind of the same thing, but it's got a bad rap because it's been used by a whole bunch of people that don't know what they're talking about. So I really don't like that term anti-aging. But aging as a disease and longevity are perfectly valid ways to talk about this subject.

0

64.521 - 85.258 Dr. David Sinclair

So let's talk about aging as a disease. When I started my research, disease here at Harvard Medical School, it was considered if there's something that's wrong with you, and it's a rare thing, has to be less than 50% of the population, that's definitely a disease. And then people work their whole lives to try and cure that condition.

0

85.318 - 102.398 Dr. David Sinclair

And so I looked up what's the definition of aging, and it says, well, it's a deterioration in health and sickness, and you can die from it, typically you do. So I'm thinking that sounds pretty much like a disease, but the caveat is that if more than half the population gets this condition, aging,

102.496 - 121.177 Dr. David Sinclair

It's put in a different bucket, which is, first of all, that's outrageous because it's just a totally arbitrary cutoff. But think about this, that we're ignoring the major cause of all these diseases. Aging is 80% to 90% the cause of heart disease, Alzheimer's. If we didn't get old and our bodies stayed youthful, we would not get those diseases.

121.237 - 141.617 Dr. David Sinclair

And actually, what we're showing in my libels, if you turn the clock back in tissues, those diseases go away. So aging is the problem. And instead, through most of the last 200 years, we've been sticking Band-Aids on diseases that have already occurred because of aging. And then it's too late. So there are a couple of things. One is we want to slow aging down so we don't get those diseases.

142.138 - 147.187 Dr. David Sinclair

And when they do occur, don't just stick a Band-Aid on, reverse the age of the body, and then the diseases will go away.

147.708 - 155.723 Andrew Huberman

That clarifies a lot for me. Thank you. Can we point to one specific general phenomenon in the body that underlies aging?

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