Rapamycin for Anti-Aging: the latest science

From National Geographic: Rapamycin (red) inhibits a protein complex called mTORC1 (mammalian target of rapamycin complex 1, blue). It is mainly used to prevent rejection in organ transplantation, but some people are taking the drug for possible anti-aging benefits. So far, those benefits have not been proven in humans. (I wrote about MTOR in my book, and we discussed it here, too.)

The quest for the fountain of youth may go back centuries, but it’s only in the past two decades that scientists may be close to finding it—at least as it pertains to yeast, flies, and mice.

The elixir of interest to both researchers and longevity seekers is the prescription drug rapamycin. Some anti-aging influencers like Peter Attia, a physician and popular podcaster who devoted a chapter to the drug in his recent bestseller, Outlive, are enamored by its possibilities. But whether it truly extends life and expands people’s disease-free years remains an unanswered question.

Years of research in mice have shown that rapamycin “is the most robust and reproducible drug” when it comes to increasing lifespan and slowing the aging process, says Matt Kaeberlein, a longtime rapamycin researcher at the University of Washington in Seattle who recently cofounded a for-profit longevity technology company, Optispan. “If you take old mice where there’s already been a decline in function and you start treating them with rapamycin, the function comes back up.”

Some people have seized on these results to take low doses of the drug now, despite the many unknowns about its efficacy and safety. They’re able to do so because the medicine was approved by the U.S. Food and Drug Administration in 1999 to help suppress the immune system in people receiving an organ transplant; once a drug is available, doctors can prescribe it for any condition.

But “waiting for the science is probably the safe move,” says Dudley Lamming, head of the molecular physiology of aging lab at the University of Wisconsin-Madison, who coauthored a comprehensive review of research on rapamycin in Nature Aging last year.

What does rapamycin do in the body?

Rapamycin works by suppressing a signaling enzyme known as mTOR (short for mechanistic target of rapamycin), which is a fundamental decision maker for most cells in the body and brain. The protein’s main purpose is to sense whether nutrition is available or in short supply. When food is abundant, mTOR broadcasts for cells to grow and divide.

When food is scarce, cells reduce their replication. The body instead shifts to pruning and tuning existing tissue. Anyone who spent time during the COVID-19 lockdowns mending all the previously neglected parts of their home can undoubtedly relate.

“The cells focus their energy into recycling damaged proteins, repairing damaged organelles like mitochondria, and upregulating other cellular defenses that might help, for instance, keep the genomic DNA intact and stable,” Lamming says.

The result is cells, tissues, and organ systems that are healthier than before.

The nutrition-sensing action is so important that mTOR is present in nearly every organism, from single-celled amoeba to humans, which makes sense from an evolutionary perspective, Kaeberlein says. During periods of famine, the successful strategy “is to become stress resistant, survive long enough that you can still be reproductively active when the famine is over,” he says.

Studies have long shown that mice that eat fewer calories live longer, and scientists now speculate that the resulting reduction in mTOR may at least partially drive this phenomenon. That makes mTOR inhibiting drugs like rapamycin appealing candidates for extending the human lifespan or health span, which are the years a person lives without debilitating ailments.

From Rapa Nui to the research lab

Rapamycin was discovered by chance in 1964 when Canadian scientists came to the South Pacific’s Easter Island to study the health of its native inhabitants. They discovered a potent antifungal agent in the soil samples they brought back, and biochemist Suren Sehgal named the compound rapamycin (after Rapa Nui, the indigenous name for the island).

When the pharmaceutical company he worked for merged and shut his lab, Sehgal stashed a jar of the compound in his home freezer until 1987, when he was able to resume the work. The drug proved such a potent immune system modulator that Wyeth Pharmaceuticals received FDA approval to market a high-dosage, daily regimen to prevent organ rejection. (A chemically similar drug, everolimus, was approved to treat cancers in 2016.)