Everything you need to know about reversing biological aging — from the basics of what aging actually is, to the specific protocols David Sinclair and others use every day.
Here's the short version: your body has a biological age and a chronological age. Your chronological age is how many years you've been alive. Your biological age is how old your cells, tissues, and organs actually function. These two numbers don't have to match.
Scientists have discovered that aging isn't just "time passing." It's a collection of specific, measurable processes happening inside your cells. And many of those processes can be slowed — or even partially reversed — with the right interventions.
Think of it like this: your DNA is like a piano. The songs that get played depend on which keys are pressed — that's your epigenome. As you age, the wrong keys start getting pressed. Longevity research is largely about figuring out how to reset which keys are active.
You can't stop aging, but you can meaningfully slow it and improve how you function at every age. The most evidence-backed interventions are also the least glamorous: sleep, exercise, diet, and stress management. Supplements and drugs come after you've nailed those.
The Big Four Foundations (Do These First):
The hallmarks of aging (Lopez-Otin et al., 2013; updated 2023) define 12 primary mechanisms driving biological aging. The four most targetable with current interventions:
David Sinclair's Information Theory of Aging posits that aging is fundamentally a loss of epigenetic information — not DNA mutation. The epigenome (histone modifications, DNA methylation patterns) becomes noisy over time, causing cells to lose their identity and function. Yamanaka factor partial reprogramming (OCT4, SOX2, KLF4) has demonstrated reversal of epigenetic age in multiple tissue types in mice, with early human trials underway.
NAD+ (nicotinamide adenine dinucleotide) declines approximately 50% between age 40 and 60. It is the cofactor for sirtuins (SIRT1-7) — the master regulators of cellular stress response, DNA repair, and metabolic efficiency. NMN (nicotinamide mononucleotide) and NR (nicotinamide riboside) are precursors that raise NAD+ levels. A 2023 human trial (Pencina et al.) demonstrated NMN at 1g/day increased muscle NAD+ by ~12% in older adults and improved insulin sensitivity.
mTOR (mechanistic target of rapamycin) is the primary nutrient-sensing pathway. Chronic mTOR activation suppresses autophagy — the cellular recycling process that clears damaged proteins and organelles. Rapamycin (sirolimus), an mTOR inhibitor, consistently extends lifespan in multiple model organisms. The Interventions Testing Program (NIA) has replicated longevity benefits of rapamycin in mice starting even at middle age. Intermittent fasting achieves similar mTOR suppression via nutrient restriction.
Cellular senescence — cells that stop dividing but don't die — accumulates with age and secretes the senescence-associated secretory phenotype (SASP), a pro-inflammatory cocktail that damages surrounding tissue. Senolytics (quercetin + dasatinib is the most studied combination) selectively clear senescent cells. Mayo Clinic trials have shown meaningful reductions in senescent cell burden and physical function improvements in older adults.
| Compound | Dose | Timing | Mechanism |
|---|---|---|---|
| NMN | 1g/day | Morning with yogurt | NAD+ precursor, SIRT1 activation |
| Resveratrol | 1g/day | Morning with olive oil | SIRT1 activator (requires fat for absorption) |
| Metformin | 500-850mg | Evening (not pre-workout) | AMPK activation, mTOR suppression |
| Berberine | 500mg 2-3x | With meals | AMPK activation, glucose control (Metformin alternative) |
| Vitamin D3+K2 | 4000-5000 IU D3 | Morning | Epigenetic regulation, bone/immune function |
| Quercetin | 500mg | Intermittent (senolytic) | Senescent cell clearance |
| Spermidine | 1mg/day | Morning | Autophagy induction, epigenetic protection |
Note: This reflects publicly stated information from Sinclair's podcast appearances and book. Not a prescription. Metformin is Rx-only in the US and has tradeoffs, particularly around blunting exercise adaptations.
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