Dr. David Sinclair: Professor of genetics at Harvard Medical School and co-director of the Paul F. Glenn Center for the Biology of Aging. A leading aging researcher known for his work on sirtuins and the epigenome, and author of the New York Times bestseller 'Lifespan.'
What this episode covers
Andrew Huberman interviews Harvard geneticist David Sinclair about the biology of aging, framed around Sinclair's central claim that aging is a disease driven by loss of epigenetic information rather than an inevitable fate. They go deep on mechanism, including the epigenome as a 'scratched CD,' the role of sirtuins, NAD, and the mTOR pathway, and how DNA damage and stress accelerate aging. Sinclair shares his personal protocol in detail: skipping meals, eating in a narrow window, and supplementing with resveratrol, NMN, metformin, and a statin, all dissolved in fat and timed to the body's natural cycles. The conversation also covers cholesterol myths, iron and senescence, biomarker tracking, cold exposure, and Sinclair's lab work reversing the age of cells, including restoring vision in blind mice. It closes on the importance of measuring biological age and scientists communicating directly with the public.
Recommended on this episode
Metformin
(generic prescription drug)
“there are times when I'm taking the drug Metformin, which mimics low energy.”— David Sinclair
Berberine
(supplement)
“I think berberine has been shown to be really safe in humans.”— David Sinclair
Resveratrol
(supplement)
“you can only get the thousand milligrams that I take a day from a supplement that's pure.”— David Sinclair
NMN (nicotinamide mononucleotide)
(supplement)
“I take a precursor to NAD called NMN and the body uses that to make the NAD molecule in one step.”— David Sinclair
The guest's own work
Lifespan: Why We Age And Why We Don't Have To
David Sinclair
“The title of that book, is 'Lifespan: Why We Age And Why We Don't Have To.'”— Andrew Huberman
Also referenced (named, not recommended)
The Warrior Diet
Ori Hofmekler
“He wrote a book called 'The Warrior Diet', which got very little attention at the time.”— Andrew Huberman
NR (nicotinamide riboside)
(supplement)
“You can take NR, which is used to make an amend, which is used to make NAD, and both NMN and NR are sold by companies in the US.”— David Sinclair
Quercetin
(supplement)
“there's another one called quercetin, or quercetin, some people call it, what you find in trace amounts in apples and onions.”— David Sinclair
Statin
(generic prescription drug)
“So I went on a statin, and I know there's a lot of people who say that statins long-term are bad.”— David Sinclair
PCSK9 inhibitor
(generic prescription drug)
“There's one called the PCSK9 inhibitor, which is, I think fortnightly, every two weeks injection, that blocks the release of LDL from the liver.”— David Sinclair
Deadpool
Marvel
“The future of humanity is more like us walking around like Deadpool.”— David Sinclair
The Wizard of Oz
MGM
“the people who played the munchkins in the Wizard of Oz, many of them went on to live into their nineties and beyond.”— David Sinclair
Diet Coke
Coca-Cola
“Joe Rogan laughed at me 'cause I was drinking a diet coke during the first interview I did with them. I will drink diet coke”— David Sinclair
Big reveals from this episode
- Sinclair argues aging is classified as 'not a disease' only because more than half the population gets it, calling the cutoff arbitrary and outrageous.
- Sinclair admits he's never publicly discussed that periods of immense vitality like puberty are also periods of fastest biological aging.
- Slower physical development in youth is predictive of a longer, healthier life, and growth hormone is pro-aging.
- Buried in supplemental data nobody reads: mice given resveratrol every other day on a normal diet lived dramatically longer, some over three years.
- Sinclair debunks the myth that metformin blocks muscle gains, saying it only costs about 5% muscle size while lowering inflammation.
- Citing a study Peter Attia flagged, Sinclair says dietary cholesterol has almost zero impact on blood cholesterol, regretting decades of avoiding eggs and butter.
- Sinclair claims he lowered his InsideTracker biological age from 58 to 31 in a matter of months.
- His lab's Nature paper reversed the age of retinal neurons and restored sight in blind mice, with human blindness trials targeted for 2022-2023.
Worth remembering
- Sinclair boils aging down to an equation: the loss of information due to entropy, comparing it to scratches on a CD.
- Your DNA is six feet long per cell; joined together your chromosomes could reach the moon and back eight times.
- A mouse in Sinclair's lab, nicknamed 'Yoda,' lived five years (versus the typical two) via caloric restriction plus a low-growth-hormone dwarf mutation.
- Going three days without eating triggers chaperone-mediated autophagy, a deep cellular cleanse that made old mice live 35% longer.
- Fasting raises sirtuins and lowers mTOR (via low leucine, lysine, valine), and that combination turns on the body's defenses.
- An enzyme called CD38 chews up NAD as you age, so you both make less and lose more, a double whammy.
- Taking NMN for about two weeks roughly doubles NAD blood levels, per unpublished clinical trials.
- NMN restored fertility to 16-month-old infertile female mice within six weeks, suggesting female mammals don't simply run out of eggs.
- Excess iron is pro-senescent, increasing zombie cells that drive inflammation and cancer, so Sinclair avoids iron supplements.
- Sinclair quality-checks his NMN by taste: real white crystalline NMN should taste like burnt popcorn.