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

Oct 30, 2025 39m 7s 24 insights
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.
Actionable Insights

1. Focus on Reversing Aging

Focus on slowing down and reversing aging to prevent and treat diseases, rather than just treating symptoms of age-related diseases, as aging is the primary cause of many illnesses.

2. Prioritize Epigenetic Control

Understand that 80% of future longevity and health is controlled by epigenetic information, which dictates gene expression and can be influenced by lifestyle choices.

3. Embrace Hunger Periodically

Avoid constant eating and periodically experience hunger, as this activates longevity genes and can lead to a longer, healthier life by preventing the constant activation of growth pathways.

4. Skip One Meal Daily

Try to skip one meal a day (either breakfast or dinner) to activate longevity genes, especially when combined with the sleep period, to extend the fasting window.

5. Persevere Through Initial Fasting

Persist through the initial two to three weeks of hunger and habit changes when implementing fasting, as the body and brain will adapt to the new routine.

6. Try Longer Fasts Monthly

Consider longer fasts (2-3 days, perhaps once a month) to trigger deeper cellular cleansing processes like chaperone-mediated autophagy, which can lead to significant longevity benefits.

7. Fasting Activates Sirtuins, Lowers mTOR

Fasting activates sirtuins and downregulates mTOR (due to lack of amino acids), which collectively turn on the body’s defenses, improve insulin sensitivity, repair cells, and provide energy.

8. Induce Cellular Adversity

Introduce periods of perceived adversity (e.g., through fasting or exercise) to cellular systems, as constant comfort leads to relaxed cells and accelerated aging.

9. Rational, Gradual Fasting Approach

Adopt a rational and flexible approach to fasting, allowing for small indulgences and gradually implementing changes rather than going ‘cold turkey’ to increase adherence and enjoyment.

10. Pulse Supplements and Activities

Recognize that constant consumption of supplements or continuous activity may not be optimal; instead, consider pulsing these activities to allow the body to perceive adversity and respond effectively.

11. Maintain Muscle Mass

Prioritize maintaining muscle mass through exercise to support hormone levels, which is crucial for overall health and longevity, especially as one ages.

12. Aerobic Exercise for Sirtuins

Engage in aerobic exercise to naturally raise NAD levels and activate sirtuin genes (specifically sirt1 and sirt3), which are beneficial for longevity.

13. Consider NMN Supplementation

Consider supplementing with NMN (a precursor to NAD) to potentially double NAD levels in the blood within about two weeks, which is important for sirtuin activity.

14. Monitor HSCRP for Inflammation

Get an HSCRP (high-sensitive C-reactive protein) reading, as it’s a strong predictor of cardiovascular inflammation and longevity; if levels are high, prioritize bringing them down quickly.

15. Lower HSCRP via Diet

Lower high HSCRP levels by adjusting your diet to eat less and consume more vegetables, as diet is a key factor in inflammation.

16. Monitor HbA1c Levels

Monitor your HbA1c levels to understand your average blood glucose over the month, which is a key indicator of metabolic health and aging.

17. Monitor Iron Levels

Be aware that excess iron can accelerate aging by increasing senescent cells, which cause inflammation and can lead to cancer; therefore, monitor your iron levels.

18. Track Health Data Long-Term

Regularly track blood work and other health markers over long periods (e.g., a decade or more) to gain informative insights into personal health trends and variations.

19. Personalize Health Approaches

Personalize health approaches by tracking individual data over time to determine what’s optimal for your body, rather than relying solely on average human recommendations.

20. Electrolytes: Use As Needed

While some people may benefit from ingesting electrolytes during fasting to prevent lightheadedness or shakiness, it’s not universally necessary if you don’t experience those symptoms.

21. Consider Leucine’s Pro-Aging Effect

Be aware that leucine, while beneficial for muscle growth, may be pro-aging in the long term due to its activation of the mTOR pathway.

22. Fasting Delays Infertility (Animals)

Caloric restriction or fasting can potentially delay infertility in female animals and rejuvenate the reproductive system, though this is not a direct recommendation for humans to become ‘super skinny’.

23. Rejuvenate Female Fertility

The female reproductive system may be rejuvenatable, potentially even restoring fertility after it has ceased, challenging previous biological understanding.

24. Harness Body’s Healing Powers

Recognize the body’s remarkable capacity for healing, recovery, and rejuvenation, understanding that systems can be reset and repaired in ways previously thought impossible.