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

1. Skip One Meal Daily

Skip either breakfast or dinner to extend your fasting window, combining it with your sleep period. This activates longevity genes (sirtuins) and cellular defense systems, and downregulates mTOR, which is hugely beneficial for longevity and cellular repair.

2. Consider Longer Fasts (2-3 Days)

Occasionally (e.g., once a month), fast for 2-3 days to trigger deep cellular cleansing processes like chaperone-mediated autophagy, which digests old and misfolded proteins and has been shown to significantly extend lifespan in animals.

3. Reduce Sugar and Simple Carbs

Eliminate or significantly reduce dessert, sugar, and simple carbohydrates like bread from your diet. This helps maintain low blood glucose and insulin levels, activating longevity genes and improving overall health, including dental plaque reduction.

4. Supplement NMN Daily

Take 1 gram of NMN (Nicotinamide Mononucleotide) daily, preferably in the morning, as it is a crucial ‘fuel’ for sirtuin activity. This can double NAD levels in the blood within approximately two weeks, supporting cellular defenses and energy.

5. Supplement Resveratrol Daily

Take 1 gram of pure resveratrol daily with a fatty substance like olive oil or yogurt to significantly increase absorption. Resveratrol acts as an ‘accelerator pedal’ for sirtuin enzymes, boosting their activity to clean up and protect the body.

6. Take Supplements with Fat

Always ingest resveratrol and other ‘crunchy’ supplements like quercetin or curcumin with a fatty substance (e.g., olive oil, yogurt). This significantly increases their absorption into the bloodstream, making them more effective.

7. Prioritize Plant-Rich Diet

Adopt a diet primarily rich in vegetables, especially dark leafy greens, for high-density nutrition and beneficial ‘xenohormetic molecules.’ These molecules are produced by stressed plants and activate the body’s natural defenses against aging.

8. Exercise for Muscle Mass

Engage in regular exercise to maintain muscle mass, which is vital for preserving natural hormone levels (e.g., testosterone) and overall vitality as you age. This also contributes to a younger biological age.

9. Avoid Excess Iron Supplements

Do not take excess iron supplements unless medically necessary, as excess iron is a ‘pro-senescent metal’ that increases zombie-like senescent cells. These cells secrete inflammatory molecules, accelerating aging and increasing cancer risk.

10. Consider Metformin (Prescription)

Consult a doctor about Metformin, a prescription drug that mimics low energy and has epidemiological data suggesting longevity benefits and protection against cancer, heart disease, frailty, and dementia. Skip it on exercise days to avoid stamina reduction.

11. Consider Berberine (Supplement)

Explore Berberine as a supplement, which works similarly to Metformin by boosting cellular energetics and increasing insulin sensitivity. Take high doses to maximize its beneficial effects on metabolism and anti-type 2 diabetes action.

12. Track Health Biomarkers Regularly

Regularly track a comprehensive panel of health biomarkers (e.g., HbA1c, HS-CRP, cholesterol ratios) over time, ideally annually or semi-annually. This provides personalized data to understand trends and optimize health decisions beyond average ranges.

13. Monitor HS-CRP Levels

Pay attention to your High-Sensitivity C-Reactive Protein (HS-CRP) levels, as it is a key marker for cardiovascular inflammation and a predictor of longevity. If levels are high, reduce them quickly through diet (less food, more vegetables) or anti-inflammatory drugs.

14. Limit DNA Damage Exposure

Minimize exposure to sources of DNA damage such as X-rays (e.g., limit routine dental X-rays, opt for pat-downs at airports) and excessive sun exposure, as these accelerate epigenome disruption and the aging process.

15. Prioritize NMN over NR/B3

When choosing an NAD precursor, select NMN over NR (Nicotinamide Riboside) or Vitamin B3 (Niacin). NMN provides all necessary components for NAD synthesis and has shown superior effects in studies, such as increased endurance.

16. Sleep Cool, Dress Lightly

Incorporate ‘metabolic winter’ practices by sleeping in a cool environment and dressing lightly. This promotes slight energy expenditure throughout the night, mimicking ancestral conditions of cold exposure and potentially aiding in weight management.

17. Maintain Proper Hydration & Electrolytes

Ensure adequate hydration and electrolyte intake (sodium, magnesium, potassium) for optimal brain and body function. Drink electrolytes first thing in the morning and during physical exercise to prevent diminished cognitive and physical performance.

18. Use Stevia as Sweetener

Opt for stevia as a sweetener, as it is a naturally sourced product and currently lacks strong evidence of negative health effects, unlike some artificial sweeteners.

19. Practice Yoga Nidra or NSDR

Utilize Yoga Nidra or Non-Sleep Deep Rest (NSDR) protocols, even for short 10-minute sessions, to significantly restore levels of cognitive and physical energy and achieve different brain and body states.

20. Avoid Excessive Growth Hormone

Be cautious with excessive growth hormone intake if your goal is long-term longevity, as research suggests it is a ‘pro-aging’ factor that can accelerate the body’s aging processes despite immediate vitality benefits.

21. Don’t Over-Restrict Dietary Cholesterol

Do not overly restrict dietary cholesterol from foods like eggs and butter. Recent studies indicate that dietary cholesterol has minimal impact on blood cholesterol levels compared to the body’s own synthesis.

22. Seek Stressed Plants

When selecting produce, look for plants that have experienced some environmental stress (e.g., brightly colored, sun-exposed, slightly damaged). These plants may contain more beneficial xenohormetic molecules that activate your body’s defenses.

23. Supplement Quercetin

Consider supplementing with quercetin (found in apples and onions), as it activates sirtuins and helps kill senescent (zombie) cells, offering a dual benefit for anti-aging.

24. Avoid Mega-Doses of Antioxidants

Do not take mega-doses of antioxidants. The body requires some oxidants for immune system function and mitochondrial health (mitohormesis), and excessive intake has not shown significant longevity benefits.

25. Start New Habits Gradually

When adopting new dietary or lifestyle habits, such as fasting, introduce changes gradually rather than going ‘cold turkey.’ This approach increases the likelihood of long-term success and adaptation.

26. Use GMP Certified Supplements

When purchasing NMN or any other supplements, always look for ‘GMP’ (Good Manufacturing Practices) certification. This ensures high levels of quality control, product integrity, and that the supplement contains what it claims.

27. Reset Circadian Clock with NMN

When traveling across time zones, take a boost of NMN in the morning to help reset your circadian clock to the new time zone, potentially alleviating jet lag.

28. Reduce Hypothalamic Inflammation

Focus on reducing inflammation in the hypothalamus, a key brain region, through lifestyle and diet. Inhibiting inflammation in this area has been shown to extend lifespan in animals by maintaining GNRH expression.

29. Utilize Biological Age Testing

Consider utilizing emerging biological age tests (e.g., simple mouth swabs) to get a ‘credit score for the body.’ This allows for personalized tracking and optimization of health and longevity efforts, as you cannot optimize what you don’t measure.

30. Supplement Vitamin D3 & K2

Supplement with Vitamin D3 and K2. D3 is essential for brain and body health, as many are deficient even with sun exposure. K2 regulates cardiovascular function and calcium in the body.