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

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.
Aging is framed not just as natural decline but as a treatable condition rooted in epigenetic dysfunction—specifically, the loss of gene regulation over time, akin to 'scratches' on a CD disrupting cellular function. The epigenome, influenced heavily by environment and behavior, governs up to 80% of health outcomes. Key strategies like fasting activate sirtuins, longevity genes dependent on NAD, which decline with age. Fasting lowers glucose and insulin, inhibiting mTOR and promoting autophagy—a cellular 'deep clean.' NMN supplementation boosts NAD, enhancing sirtuin activity. Exercise further supports this system by increasing NAD and maintaining muscle health. Excess iron may accelerate aging via senescent cells, highlighting the need for personalized health approaches. Blood markers like CRP help track inflammation and guide interventions. Remarkably, fasting and NMN have shown potential to reverse reproductive aging in mice, suggesting rejuvenation is biologically possible. The conversation emphasizes practical tools—skipping meals, pulsing fasting and feeding, monitoring biomarkers—while balancing longevity goals with quality of life.
00:20
00:20
Aging is the major cause of many chronic diseases and should be classified as a disease itself.
02:27
02:27
80% of future longevity and health is controlled by epigenetic information
04:55
04:55
Aging disrupts methylation patterns, leading to loss of cell identity and disease.
06:44
06:44
Centenarian families often look younger than their age
08:56
08:56
Genes that cause aging are early developmental genes.
11:30
11:30
Animals with low growth hormone often live longest
12:43
12:43
80% of health is determined by epigenetics, not genes
16:05
16:05
Low glucose levels make muscles and the brain more insulin-sensitive, pulling glucose from the blood.
16:34
16:34
Skipping a meal a day extends the fasting window and supports metabolic health
17:11
17:11
Triggering autophagy in old mice can extend their lifespan by 35%
20:16
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
24:28
A staged approach to fasting improves long-term adherence
28:00
28:00
NMN can double NAD levels in the blood after about two weeks
31:10
31:10
Healthy people with low iron from plant-based diets often have high energy levels.
32:41
32:41
CRP is an early marker for various diseases and a predictor of longevity
34:55
34:55
Aerobic exercise in rodents raises NAD levels and gene expression
36:15
36:15
NMN can rejuvenate the female reproductive system in old mice
38:22
38:22
The discussion on lifespan mechanisms was illuminating.