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

Overview

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

Huberman Lab

Oct 30
Huberman Lab

Huberman Lab

Oct 30
OverviewShownoteHighlightsTranscriptChaptersPins

Shownote

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

Highlights

In this episode, Dr. Andrew Huberman revisits foundational longevity science with Dr. David Sinclair, a leading expert in genetics and aging from Harvard Medical School. The discussion dives into the biological underpinnings of aging, focusing on cellular mechanisms that influence how we age and how lifestyle interventions can modulate these processes for better healthspan.
00:20
Aging is the major cause of many chronic diseases and should be classified as a disease itself.
02:27
80% of future longevity and health is controlled by epigenetic information
04:55
Aging disrupts methylation patterns, leading to loss of cell identity and disease.
06:44
Centenarian families often look younger than their age
08:56
Genes that cause aging are early developmental genes.
11:30
Animals with low growth hormone often live longest
12:43
80% of health is determined by epigenetics, not genes
16:05
Low glucose levels make muscles and the brain more insulin-sensitive, pulling glucose from the blood.
16:34
Skipping a meal a day extends the fasting window and supports metabolic health
17:11
Triggering autophagy in old mice can extend their lifespan by 35%
20:16
Sirtuins respond to low sugar and insulin, while mTOR is activated by amino acids like leucine, creating a balance between longevity and aging signals.
24:28
A staged approach to fasting improves long-term adherence
28:00
NMN can double NAD levels in the blood after about two weeks
31:10
Healthy people with low iron from plant-based diets often have high energy levels.
32:41
CRP is an early marker for various diseases and a predictor of longevity
34:55
Aerobic exercise in rodents raises NAD levels and gene expression
36:15
NMN can rejuvenate the female reproductive system in old mice
38:22
The discussion on lifespan mechanisms was illuminating.

Chapters

David Sinclair
00:00
Longevity, Anti-Aging, Aging as a Disease
00:20
Causes of Aging; Epigenome & Genes
02:27
CD & Scratches Analogy, DNA, Silencing & Expressing Genes
04:53
Physical Appearance & Aging
06:44
Sponsor: David
07:36
Childhood Development & Aging, Horvath Clock, Accelerate Aging
08:54
Rates of Puberty & Aging, Growth Hormone
11:30
Body Size & Longevity; Epigenetics
12:37
Fasting, Calorie Restriction & Longevity, Sirtuins, Insulin & Glucose
13:07
Tool: Skip a Meal
16:31
Longer Fasts & Autophagy, “Deep Cleanse”
17:07
Sponsor: AGZ by AG1
18:07
Fasting, Fluids, Electrolytes
19:36
Sirtuins, Glucose, mTOR & Fasting; Leucine, Tool: Pulsing Behaviors
20:16
Breaking a Fast, Tools: Do Your Best; Transitions
24:24
Sirtuins, NAD, NMN Supplementation
27:00
Sponsor: Eight Sleep
29:04
Iron & Senescent Cells; Personalize Medicine
31:10
Tool: Blood Markers, CRP
32:40
Tool: Aerobic & Resistance Exercise
34:50
Estrogen, Fasting & Fertility; Aging & Rejuvenation
35:55
Acknowledgements
38:20

Transcript

Speaker 1: 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 ophthalmo...