Dr. David Sinclair on Huberman Lab: Why Aging Is Erasable

Aging is loss of epigenomic information, like a scratched CD; fasting activates sirtuins to slow the clock, and NMN restores NAD levels that drop with age.

Andrew HubermanhostDavid Sinclairguest

Oct 30, 202533mWatch on YouTube ↗

EPISODE INFO

Released: October 30, 2025
Duration: 33m
Channel: Huberman Lab
Watch on YouTube: ▶ Open ↗

EPISODE 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. Episode show notes: https://go.hubermanlab.com/MW6SYCf Huberman Lab Essentials are short episodes focused on essential science and protocol takeaways from past full-length Huberman Lab episodes. Watch the full-length episode: https://youtu.be/n9IxomBusuw Watch more Huberman Lab Essentials episodes: https://youtube.com/playlist?list=PLPNW_gerXa4OGNy1yE-W9IX-tPu-tJa7S *Follow Huberman Lab* Instagram: https://www.instagram.com/hubermanlab Threads: https://www.threads.net/@hubermanlab X: https://twitter.com/hubermanlab Facebook: https://www.facebook.com/hubermanlab TikTok: https://www.tiktok.com/@hubermanlab LinkedIn: https://www.linkedin.com/in/andrew-huberman Website: https://www.hubermanlab.com Newsletter: https://www.hubermanlab.com/newsletter *Timestamps* 00:00:00 David Sinclair 00:00:20 Longevity, Anti-Aging, Aging as a Disease 00:02:27 Causes of Aging; Epigenome & Genes 00:04:53 CD & Scratches Analogy, DNA, Silencing & Expressing Genes 00:06:44 Physical Appearance & Aging 00:07:36 Childhood Development & Aging, Horvath Clock, Accelerate Aging 00:10:13 Rates of Puberty & Aging, Growth Hormone 00:11:20 Body Size & Longevity; Epigenetics 00:11:50 Fasting, Calorie Restriction & Longevity, Sirtuins, Insulin & Glucose 00:15:14 Tool: Skip a Meal 00:15:50 Longer Fasts & Autophagy, “Deep Cleanse”; Fluids, Electrolytes 00:17:28 Sirtuins, Glucose, mTOR & Fasting; Leucine, Tool: Pulsing Behaviors 00:21:37 Breaking a Fast, Tools: Do Your Best; Transitions 00:24:13 Sirtuins, NAD, NMN Supplementation 00:26:18 Iron & Senescent Cells; Personalize Medicine 00:27:48 Tool: Blood Markers, CRP 00:29:57 Tool: Aerobic & Resistance Exercise 00:31:02 Estrogen, Fasting & Fertility; Aging & Rejuvenation 00:33:28 Acknowledgements Disclaimer & Disclosures: https://www.hubermanlab.com/disclaimer

SPEAKERS

Andrew Huberman
host
David Sinclair
guest

EPISODE SUMMARY

In this episode of Huberman Lab, featuring Andrew Huberman and David Sinclair, Dr. David Sinclair on Huberman Lab: Why Aging Is Erasable explores rewriting the Aging Clock: Fasting, Epigenetics, and Longevity Pathways Explained Andrew Huberman and David Sinclair discuss the biology of aging, arguing that aging should be treated as a disease driven largely by loss of epigenetic information, not just by genetic damage. Sinclair explains how changes in the epigenome—“scratches” on the cellular information system—disrupt cell identity and drive most age-related diseases. They outline how behaviors like intermittent fasting, caloric restriction, and exercise activate longevity pathways (notably sirtuins and mTOR) that slow or even reverse aspects of aging in animal models. Practical protocols around fasting, supplementation (e.g., NMN), iron management, and blood biomarkers are discussed, along with emerging findings on fertility, senescent cells, and personalized longevity strategies.

RELATED EPISODES