Sinclair Longevity Protocol
Trigger the body's ancient survival defenses to slow and reverse aging
- Difficulty
- Moderate
- Time to result
- ~ongoing to results
- Steps
- 6
- Confidence
- 78%
Sinclair's protocol works by mimicking the adversity our ancestors faced, which switches on longevity pathways — the sirtuins (SIRT genes), mTOR, and AMP kinase. Being hungry or physically stressed tells the body 'resources are scarce, hunker down and build a durable body,' boosting NAD, the molecule sirtuins need to protect the epigenome and repair DNA. The core lever is eating less, delivered as sustainable intermittent fasting. High-intensity interval training layers on a second hormetic stressor. On top, Sinclair adds NAD-boosting precursors, resveratrol to activate sirtuins, and metformin, which lowers glucose and blunts hunger. Timing matters: benefits are largest when started early in adulthood, and the goal is compressing disease into late life (health span), with longevity emerging as the payoff.
Origin
Extracted from David Sinclair's Harvard longevity research and his own two-decade self-experiment, which he began with resveratrol in his early 30s.
Core principles
- 01Aging is a treatable process, not an immutable passage of time
- 02Adversity signals (hunger, exertion) switch on longevity genes like the sirtuins
- 03When you eat and how much matters as much as what you eat
- 04Optimize health span first; a longer lifespan follows as a byproduct
- 05Start after adulthood for the biggest effect — earlier beats later
How to run it
- 1
Eat less via sustainable intermittent fasting
Adopt a fasting pattern you can actually maintain rather than the most extreme one. Sinclair prefers skipping breakfast and having a late lunch, avoiding long multi-day hunger.
Pro tip Pick the least painful protocol you'll stick with — consistency beats severity.
Watch out Calorie restriction affects fertility and hormones; women especially should monitor this.
- 2
Add high-intensity interval training
Use HIIT to stress the body in short bursts. The up-and-down of exertion and recovery activates longevity defense networks more than steady long cardio.
Pro tip Alternate hard effort with rest — the variation is the active ingredient.
- 3
Boost NAD and activate sirtuins
NAD levels roughly halve between age 20 and 50, leaving sirtuins sluggish. Take an NAD precursor and pair it with resveratrol, a molecule that helps activate the sirtuin proteins.
Pro tip Sinclair takes ~1g of an NAD booster and resveratrol each morning, mixed into yogurt.
Watch out These are self-experiments with real, largely unquantified long-term risk — not proven human therapies.
- 4
Consider metformin under medical supervision
Metformin lowers blood glucose and, via stomach upset, blunts appetite. Sinclair takes roughly half a gram to a gram each morning, below a typical diabetic dose.
Pro tip It curbs hunger, which makes fasting easier to sustain.
Watch out Prescription-only in Western countries — requires a physician; this is not medical advice.
- 5
Start early and stay consistent
In mouse studies, starting these regimens right after adulthood gives the biggest benefit; starting mid-life yields about half the effect. Earlier and consistent application compounds.
Pro tip The aging clock ticks from before birth, so there is no benefit to waiting.
Watch out Do not apply calorie restriction or these pathways to children or developing bodies.
- 6
Track biomarkers and optimize health span
Measure markers like glucose and lipids, then adjust. Aim to keep cancer, heart disease, Alzheimer's and diabetes pushed to late life rather than chasing raw years.
Pro tip If you focus on health span, lifespan becomes a byproduct.
In the wild
Genetically predisposed to obesity and diabetes, Sinclair runs the full protocol on himself. He skips breakfast and eats a late lunch, does interval exercise, and each morning takes a gram of an NAD booster, a gram of resveratrol stirred into homemade yogurt, and metformin. At 50 he maintains a BMI around 21-22 and reports healthy cardiovascular markers, which he credits to the combined regimen rather than any single element.
→ Sustained a lean, biomarker-healthy body at 50 despite a high-risk genetic background.
For 70-80 years, labs have shown that eating less extends lifespan in organisms from yeast and worms to flies, mice and monkeys. The mechanism is boosted NAD and more active sirtuins, plus modulation of mTOR and AMP kinase. Sinclair argues humans would be a biological exception if the same did not apply, which is the empirical backbone of the protocol's fasting core.
→ Consistent lifespan extension observed across nearly every species tested.
Common mistakes
Obsessing over what to eat
People fixate on the perfect diet while ignoring that when and how much you eat matter just as much. The core lever is simply eating less.
Chasing growth hormone for longevity
Anti-aging clinics push exogenous growth hormone, but there is no evidence it extends human lifespan and it may accelerate pre-existing tumors.
Expecting comfort
The beneficial stimuli — hunger and hard exercise — are deliberately uncomfortable. Staying comfortable lets the body grow complacent and deteriorate.
Is it for you?
Best for
Health-conscious adults past ~25 who want a repeatable regimen grounded in longevity science.
Not ideal for
Children, pregnant women, or anyone seeking a fixed medical prescription rather than a personal-experiment framework.
From the transcript
“If I could give one piece of advice, only one, the most important thing would be eat less.”
“If you focus on health span, lifespan is a nice byproduct of that.”
“By fasting and calorie restricting we actually boost the levels of NAD in the cell so that those repair genes and those protectors of the…”
From the episode
Can Humans Live For 1000 Years? - Professor David Sinclair - #066
Professor David Sinclair