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Rapamycin may slow aging. Here's one way the drug will be tested

A generic drug that's used to treat transplant patients has been shown to extend the life span of some animals.
Guido Mieth
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A generic drug that's used to treat transplant patients has been shown to extend the life span of some animals.

A few years back, Matt Kaeberlein was diagnosed with a frozen shoulder. “It was really bad,” he recalls. He wasn’t sleeping well and couldn’t throw a ball due to the pain. His doctor recommended physical therapy, and told him that it may take a year to get better.

Feeling frustrated, he decided to try rapamycin. In recent years, some high-profile longevity scientists have started taking the drug in hopes of fending off age-related health problems. So far, it’s untested in people taking it for anti-aging, but rapamycin has been shown to extend the lifespan of mice.

“I decided to try it,” Kaeberlein says. It was his "first foray into biohacking,” and he was very pleased with what happened next. “Within two weeks, 50% of the pain was gone,” he says. And by the end of 10 weeks, he had regained range of motion and the pain was completely gone.

“And it hasn’t come back,” he says.

Kaeberlein is no stranger to rapamycin. He’s a biologist and co-founded the Dog Aging Project to study how rapamycin influences dogs’ healthspans. He’s also the former director of the Healthy Aging and Longevity Research Institute at the University of Washington.

Rapamycin was first approved by the FDA for use in transplant patients in the late 1990s. At high doses it suppresses the immune system. At low doses, Kaeberlein says it seems to help tamp down inflammation. It works by inhibiting a signaling pathway in the body called mTOR — which seems to be a key regulator of lifespan and aging.

The drug is not approved for pain or anti-aging, but some physicians prescribe rapamycin off-label with the aim of fending off age-related conditions. Kaeberlein and his colleagues surveyed about 300 of these patients, who take low doses, and many report benefits.

But anecdotes are no replacement for science. To figure out the risks and benefits of a drug, research is needed. And that's where a dentist comes in.

Dr. Jonathan An, at the University of Washington, has been granted FDA approval to test rapamycin in patients with gum disease — a common condition that tends to accelerate with age. When he treats patients with gum disease, he says there’s not much he can do beyond cleaning and removing the plaque — a buildup of bacteria. “All we’re doing is putting a bandage on,” he says. His goal is to find and treat the underlying cause of the disease.

There’s already some evidence from transplant patients that rapamycin may help improve oral health. And as part of the study, An and his collaborators will also measure changes in participants’ microbiomes and their biological clocks.

The study will enroll participants over the age of 50 who have gum disease. They will take the drug, at various doses, intermittently for 8 weeks. Then, An will be able to determine if the drug is safe and effective.

If rapamycin has a beneficial effect he says, it will help demonstrate that it’s possible to target the root cause of the disease. “It really comes down to targeting the biology of aging,” he says.

Dr. An thinks gum disease may be a kind of canary in the coalmine of age-related diseases. For instance, gum disease is linked to a higher risk of heart disease, and maybe dementia, too. Scientists say it’s possible that bacteria in the mouth linked to periodontal disease causes inflammation, which may cause a “cascade” of damage to blood vessels, leading to problems in the heart or brain.

“If we can target that underlying biology, we predict that it might address a lot of these other underlying conditions,” An says.

Rapamycin is a generic drug, so pharmaceutical companies have little incentive to fund new research. An and his collaborators have received a grant to conduct the trial, which could open the door to further studies to determine whether rapamycin can help prevent or slow down other age-related diseases.

Eric Verdin, a physician who heads the Buck Institute for Research on Aging, says his group is fundraising for more research on rapamycin. He says there are a lot of unanswered questions, for example “what is the effect of different concentrations in a single dose?” And he wants to look for a “molecular signature” in people taking rapamycin. He wants to know more about doses and intervals, since many doctors prescribing it off-label recommend cycling on and off the drug.

Researchers are also working on other drugs that may work in similar ways, and there’s a push for new drugs — or other interventions that target biological aging. There’s a new $100 million XPRIZE Healthspan competition, aimed at accelerating the research in the field supported by Hevolution and other funders.

For now, XPRIZE founder Peter Diamandis, a physician who writes about longevity, says he takes rapamycin. “I do six milligrams every Sunday night, so once a week," for three months, he explains. Then he takes a month off. "I believe that rapamycin — in the way I'm utilizing it — is safe and has more upside potential than downside,” he says.

Diamandis constantly monitors his body with many health metrics, and he acknowledges it’s hard to determine the effect of rapamycin given all the other things he does to stay healthy, including eating well, eliminating sugar, working out every day and prioritizing sleep.

His plan is to continue with healthy lifestyle habits while supporting research into interventions and strategies that can help people add more healthy years to their life.

Find Allison Aubrey on Instagram at @allison.aubrey and on X @AubreyNPR.

This story was edited by Jane Greenhalgh

Copyright 2024 NPR

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Allison Aubrey is a correspondent for NPR News, where her stories can be heard on Morning Edition and All Things Considered. She's also a contributor to the PBS NewsHour and is one of the hosts of NPR's Life Kit.