David Sinclair might be the most interesting man in longevity science. The Harvard professor has spent 30 years studying aging, and somewhere along the way, he became his own best experiment. At 54, his blood work looks like a 31-year-old’s. That’s not genetic luck – it’s what happens when you turn your body into a living laboratory.

His book Lifespan: Why We Age and Why We Don’t Have To lays out his Information Theory of Aging. Basically, aging isn’t wear and tear – it’s corrupted software. And like any software problem, Sinclair thinks we can debug it.

The whole approach targets three master switches: sirtuins (our repair genes), mTOR (growth control), and AMPK (energy sensor). Hit these pathways right, and you’re essentially tricking your body into survival mode – where it actually maintains itself better. Here’s exactly how he does it.

1. NMN and Resveratrol: The Foundation

Every morning, Sinclair takes 1 gram of NMN and 1 gram of resveratrol as part of his daily supplement list. You may have not heard of these supplements, but the science is pretty compelling.

NMN boosts NAD+, which is basically cellular fuel. Problem is, we lose about half our NAD+ between 20 and 50. Without it, our sirtuin genes can’t do their repair work. Think of it like trying to run a Ferrari on regular gas – it’ll move, but not like it’s supposed to.

Resveratrol is the accelerator pedal. Sinclair discovered back in 2003 that it activates sirtuins, extending lifespan in everything from yeast to mice. Here’s the catch though – you need to take it with fat. Research shows absorption jumps 5x when mixed with yogurt or olive oil. Sinclair uses homemade yogurt.

He also adds 500-1000mg of TMG as insurance against methyl depletion. Long-term NMN use might drain your methyl groups, which you need for DNA repair. Better safe than sorry.

Quality is everything here. The supplement industry is like the Wild West, so stick with third-party tested brands. I use Renue By Science for both liposomal resveratrol and NMN powder – you can mix the NMN right into yogurt like Sinclair does. Use code ‘brainflow’ for 10% off.

2. Intermittent Fasting

Sinclair doesn’t eat breakfast or lunch. Just dinner, usually within an 8-hour window. But he’s not militant about it – sometimes he’ll grab a small salad if he’s actually hungry.

Morning routine? Coffee, tea, hot water, and a tiny bit of yogurt with his supplements. That’s it. He says staying hydrated makes fasting way easier, and honestly, he’s right.

The biology here is fascinating. Fasting cranks up NAD+ production, activates sirtuins, suppresses mTOR, and kicks AMPK into gear. Same pathways as the supplements, just triggered naturally. After three days, you get this deep cellular cleanup called chaperone-mediated autophagy. Obviously most of us aren’t doing 3-day fasts regularly, but even 16 hours helps.

Women might need to be more careful with fasting – hormones can get wonky. Start slow, see how you feel.

RELATED READING: Inside Andrew Huberman’s Daily Supplement Stack

3. Exercise That Actually Matters

Here’s Sinclair’s rule: be out of breath for 10 minutes every day. Not just elevated heart rate – actually huffing and puffing.

His routine is intense. A hundred push-ups every morning (I know, right?), weights once or twice a week with his son, and he never sits down – uses a standing desk with one of those under-desk steppers. The guy is constantly moving.

HIIT is the secret sauce because it creates hypoxic stress. Your cells think they’re dying, so they activate every repair mechanism they’ve got. Six months of this actually lengthens your telomeres.

Focus on legs and back especially. These big muscle groups signal your endocrine system to keep producing hormones like testosterone and growth hormone. Use it or lose it, literally.

Sinclair’s take: “Instead of killing yourself at the gym twice a week, do 20 minutes daily.” Consistency beats intensity every time. Plus you’re way less likely to get injured and quit.

RELATED READING: Andrew Huberman’s NAD+ Supplement Protocol

4. Cold Exposure

Sinclair plunges into 39°F water for 2-5 minutes, then hits the sauna. But even ending your shower with cold water works.

The numbers are crazy. Cold water at 57°F spikes noradrenaline by 530% and dopamine by 250%. You also activate SIRT3, which converts useless white fat into metabolically active brown fat. Brown fat is like a furnace – burns calories just to keep you warm.

His theory? We’re too comfortable. Our ancestors dealt with temperature swings that triggered these survival pathways. Now we live at a constant 72°F and wonder why we’re metabolically broken.

Start with 30 seconds of cold at the end of your shower. Work up from there. Yes, it sucks. Yes, you’ll hate it. But the energy boost after is undeniable, and you’ll probably stop getting sick as often. Worth it.

5. Plants Over Mammals

“I eat a lot of plants and try to avoid eating other mammals.” That’s Sinclair’s basic philosophy, but there’s nuance here.

He looks for stressed plants – the ones that had to fight to survive. Dark berries, bitter greens, colorful vegetables. These plants produce defense compounds that activate our longevity pathways when we eat them. It’s called xenohormesis – basically stealing another organism’s stress response.

Meat jacks up mTOR, which is great if you’re trying to build muscle at 25, not so great if you’re trying to live to 150. Sugar is worse – completely shuts down AMPK and sirtuins. Sinclair’s typical dinner: vegetables, nuts, whole grains, maybe some fish.

He’ll have a glass of Pinot Noir occasionally (highest resveratrol content), but jokes you’d need 52 bottles daily for a therapeutic dose. Stick to the supplements.

6. Sleep and Stress (Where He Struggles)

Here’s where Sinclair admits he’s human – he only sleeps 6 hours a night. He knows it’s not ideal but optimizes what he gets with an Eight Sleep mattress that adjusts temperature throughout the night. Cooler for deep sleep, warmer to wake up naturally.

He also tracks everything with an Oura Ring, wears blue-light blocking glasses after sunset and is in bed by 11 PM religiously. Even with just 6 hours, quality matters more than quantity.

For stress, he keeps it simple. Sinclair does a quick meditation daily and takes nature walks when possible. He also engages in kayaking on weekends. His best advice? “Surround yourself with people who are not jerks.” Chronic stress literally scrambles your epigenome – the software that tells your genes what to do. Bad sleep makes it worse by tanking NAD+ levels.

I splurged on the Bed Jet temperature mattress topper and it’s been game changing. Still working on the meditation thing though.

7. The Full Supplement Stack

Beyond NMN and resveratrol, Sinclair takes a pharmacy’s worth of stuff.

Metformin (800-1000mg) at night – it’s a diabetes drug that activates AMPK like exercise. Skips it on workout days since it can blunt exercise benefits. Fisetin (500mg) clears out senescent cells. Spermidine (1-2mg) for autophagy. Weekly rapamycin for mTOR suppression.

Daily vitamins: D3 (4,000-5,000 IU), K2 (180-360 mcg), alpha-lipoic acid (300mg), taurine (2g), baby aspirin (83mg). Recently dropped quercetin – new research suggests it might inhibit SIRT6 in younger people.

He tests everything quarterly with InsideTracker. No guessing, just data. Adjusts based on biomarkers, not feelings.

Look, you don’t need all this. Start with the basics – NMN, resveratrol, maybe metformin if your doctor’s cool with it. Add more if you want, but test regularly. These aren’t candy.

The Future Is Wild

What Sinclair’s doing now is just the warm-up. His lab is working on cellular reprogramming – literally resetting cells to a younger state using Yamanaka factors. He thinks gene therapy costs will drop from $400K to $100 in the next decade thanks to AI.

They’ve got compounds in trials showing 50-95% biological age reversal in four weeks. Four weeks! He co-founded Tally Health to make biological age testing accessible to everyone. No more guessing if this stuff actually works.

His prediction? “The first person to live to 150 has already been born.” Kids today will probably see 2125. Sounds insane until you look at the exponential progress in this field.

The cool thing about his protocol is how it all works together. Each intervention amplifies the others. It’s not about adding years to your life – it’s about adding life to your years. Healthspan, not just lifespan.

The Bottom Line

Sinclair’s approach flips aging on its head. Instead of treating symptoms, he’s hacking the source code. Every intervention – supplements, fasting, exercise, cold, diet – hits the same biological switches.

What I love is that most of this doesn’t require a PhD or a trust fund. Yeah, the supplements add up, but fasting is free. Cold showers are free. Walking is free. These practices have been around forever; we just finally understand why they work.

Start small. Pick one thing. I began with intermittent fasting, added NMN later, finally worked up the courage for cold showers. Track how you feel, get some blood work done, see what happens.

Sinclair says 80% of aging is under our control. That’s either terrifying or empowering, depending on how you look at it. For the first time in history, we might actually get to choose how we age. Not whether we age – that’s still coming for all of us – but how well we do it.

The science is moving fast. What we know today will seem primitive in 10 years. But the fundamentals – stressing your body just enough to trigger repair mechanisms – that’s probably not changing. We’re just getting better at it.

So yeah, living to 150 might sound crazy now. But so did antibiotics, organ transplants, and CRISPR. Sometimes crazy is just early.