The Cornerstone: NAD+ Boosters and Sirtuin Activators
At the heart of David Sinclair's anti-aging strategy are compounds designed to support cellular function at a fundamental level. A central focus of his work is Nicotinamide Adenine Dinucleotide (NAD+), a crucial coenzyme that declines with age, impacting cellular energy and repair.
Nicotinamide Mononucleotide (NMN)
As a precursor to NAD+, Nicotinamide Mononucleotide (NMN) is a prominent component of Sinclair's regimen. He includes NMN as he believes it helps support energy at the cellular level and supports mitochondrial health. He prefers NMN over Nicotinamide Riboside (NR), citing unpublished research that showed more extensive effects in some studies. NMN can deplete methyl groups, so he pairs it with Trimethylglycine (TMG) to maintain balance.
Resveratrol
To complement NMN, Sinclair takes resveratrol each morning, mixed with yogurt to improve its absorption. This natural compound, found in red grapes, acts as a sirtuin activator. Sirtuins are proteins that regulate cellular health and longevity, and they are dependent on NAD+ to function properly. The synergistic relationship between resveratrol and NMN is a key pillar of his protocol, though research on resveratrol's human benefits remains mixed. For further context on sirtuins and their role in longevity, the National Institutes of Health offers extensive resources, including research on their regulation and functions, available at [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8466271/].
Cellular Housekeeping and Protection: Senolytics and Autophagy
Aging is also characterized by the accumulation of senescent, or "zombie," cells that secrete inflammatory factors. Sinclair incorporates compounds known as senolytics to target these cells and supports autophagy, the body's natural cellular cleanup process.
Fisetin
Sinclair takes fisetin daily, a flavonoid with potent senolytic properties. He now favors it over quercetin, a similar compound, based on evidence suggesting fisetin may be more effective at removing senescent cells. This targeted approach aims to reduce age-related inflammation and improve overall tissue function.
Spermidine
Another compound included for its role in cellular renewal is spermidine, sourced from foods like wheat germ. Taking spermidine, Sinclair aims to trigger autophagy, the process by which the body cleans out damaged cellular components. This helps maintain healthy cells and supports overall longevity.
Metabolic and Mitochondrial Support
To maintain optimal metabolic health, Sinclair's regimen includes several supplements that support mitochondrial function and mimic the effects of fasting.
Taurine
Added to his stack more recently, Sinclair takes taurine daily. This amino acid supports heart and mitochondrial function and reduces oxidative stress. Research in animals has shown promising results for lifespan extension, although Sinclair notes the complexity of its pathway effects.
Alpha Lipoic Acid (ALA)
Sinclair has reintroduced Alpha Lipoic Acid (ALA) into his routine. This powerful antioxidant supports mitochondria and helps convert glucose into energy. While evidence regarding its direct impact on lifespan is debated, Sinclair values its role in a broader antioxidant strategy.
TMG (Trimethylglycine)
To counteract potential methyl group depletion from NMN supplementation, Sinclair takes TMG daily. TMG serves as a methyl donor, supporting vital processes like DNA and protein function and protecting the body's methyl pool.
Essential Vitamins and Anti-Inflammatory Agents
Beyond the core longevity compounds, Sinclair includes essential nutrients to ensure overall health and address inflammation, a key driver of aging.
Vitamins D3 and K2
Sinclair emphasizes the importance of Vitamin D3 and Vitamin K2 daily. These two vitamins work synergistically; D3 aids calcium absorption, while K2 directs it to bones and away from arteries, promoting cardiovascular health.
Omega-3 Fish Oil
For its anti-inflammatory and cognitive benefits, Sinclair has added fish oil, a source of EPA and DHA fatty acids, to his routine. This supports brain health and helps reduce chronic, low-grade inflammation associated with aging.
Low-Dose Aspirin
Though controversial, Sinclair has taken low-dose aspirin daily, citing its potential for reducing inflammation and certain cancer risks. He acknowledges the conflicting evidence on its cardiovascular benefits for healthy individuals and the bleeding risks involved.
Comparison of Key Longevity Supplements
To help differentiate the primary components of his regimen, the following table summarizes some key aspects.
| Supplement | Primary Purpose | How It Works |
|---|---|---|
| NMN | Boost NAD+ Levels | Precursor to NAD+, essential for cellular energy and DNA repair |
| Resveratrol | Activate Sirtuins | Activates sirtuin proteins, which depend on NAD+ for function |
| Fisetin | Senolytic Activity | Helps clear senescent "zombie" cells that cause inflammation |
| Spermidine | Induce Autophagy | Promotes cellular self-cleaning and rejuvenation |
| TMG | Methyl Support | Donates methyl groups, preventing depletion from NMN metabolism |
Important Considerations for Adopting Sinclair's Protocol
It is crucial to understand that Dr. David Sinclair's regimen is a highly personalized protocol developed with access to extensive scientific research and medical oversight. His choices may not be appropriate or safe for everyone, particularly those with pre-existing conditions or those taking other medications. Any use of prescription drugs, like metformin or rapamycin, must be done under strict medical supervision due to significant risks and potential side effects. Always consult a healthcare professional before starting any new supplement or medication regimen.
Conclusion
Dr. David Sinclair's evolving supplement protocol provides a fascinating, science-based blueprint for approaching healthy aging, but it is not a one-size-fits-all solution. While his stack includes key compounds targeting cellular energy, inflammation, and metabolic function, it’s vital to remember that these are complementary to a healthy lifestyle. A holistic approach incorporating diet, exercise, and sleep optimization remains the foundation of his longevity strategy. By focusing on scientifically-supported basics and consulting with healthcare professionals, individuals can build a personalized, data-driven approach to their own healthspan journey.
