In the Fight Against Aging, a Drug Called Rapamycin Captures Attention - WSJ

In the Fight Against Aging, a Drug Called Rapamycin Captures Attention

A kidney transplant drug has become the latest fixation of people trying to fight aging.

Some people looking to extend their lifespan have for years turned to a decades-old diabetes drug, metformin. Now, rapamycin, an immunosuppressant medication, is capturing their attention because some aging researchers believe it holds more promise.

Rapamycin was originally approved by the U.S. Food and Drug Administration to prevent organ rejection in kidney transplant patients. Scientists have studied its potential to fight aging, too, and animal studies of rapamycin have yielded encouraging results, althoughthere is little evidence of its longevity benefits in humans. 

Rapamycin’s antiaging potential has attracted more off-label users in the last five years, especially among self-described “biohackers” who relish data-driven experiments to optimize health, according to aging researchers and longevity doctors. Yet its side effects can be serious, and most doctors are wary of prescribing it off-label.

Deepak Chopra, a 76-year-old wellness author, is among rapamycin’s high-profile users. Photo: Suzanne Cordeiro/AFP/Getty Images

Deepak Chopra, the 76-year-old alternative health and wellness author with millions of social media followers, is among rapamycin’s high-profile users. He says he has taken 6mg of the drug a week for the last year and a half as part of a longevity regimen that includes supplements and two hours of yoga a day. 

Efforts to fight aging

Longevity research is challenging because it is hard to prove that one particular drug or action is responsible for extending a healthy lifespan, especially in humans, who live for decades. Some measures and medications initially yield promising results only to come up short later.

Recent studies have damped some of the enthusiasm among some biohackers and longevity researchers for the diabetes drug metformin. The more recent buzz around rapamycin has caught the eyes of biotechnology investors. Last year, Cambrian Bio, a clinical-stage biotech company, announced a licensing deal with pharmaceutical company Novartis AG aimed at identifying a compound with longevity benefits similar to those of rapamycin with fewer serious side effects.

Matt Kaeberlein co-directs a research project that includes a clinical trial on the effects of rapamycin in dogs. Photo: Tammi Kaeberlein

Studies have suggested that rapamycin can extend the lifespan of yeast, worms and flies. Studies in mice, including by the National Institute on Aging’s Interventions Testing Program in 2009, have also shown an increase in lifespan.

Rapamycin is part of a group of drugs known as mTOR inhibitors. The drugs curb a cellular pathway that is responsible for cell growth in mammals. Aging researchers have found slowing down cell growth can help prevent chronic inflammation and spur autophagy, or the process of cleaning out damaged cells. 

Autophagy naturally decreases with age, which can lead to a buildup of cellular “junk” that makes it harder for cells to repair themselves and work efficiently, says researcher Matt Kaeberlein, who co-directs the Dog Aging Project, a research project that includes a clinical trial on the effects of rapamycin in dogs.  

Reducing inflammation and clearing away damaged cells could help prevent or delay the development of age-related disease such as cancer, researchers say. 

Weighing the risks

Most doctors remain cautious. 

Rapamycin’s FDA label warns users may become more susceptible to infection and the possible development of lymphoma, noting that only physicians who are experts in immunosuppressive therapy should prescribe it. Research on transplant patients, who often take higher, more frequent doses of the drug compared with those who take it for longevity, showed some of the most common side effects were high blood pressure and cholesterol levels, mouth ulcers, and the loss of kidney function. 

That hasn’t thwarted the enthusiasm for the drug within the biohacking community and among some scientists who study aging, whosay that taking a weekly dose of the drug—rather than daily, as most transplant patients do—may reduce negative side effects and even improve immune response.

Some doctors at longevity-focused clinics and telehealth apps say they are writing off-label prescriptions to patients. The drug, also called sirolimus, is sold by Pfizer Inc. under the brand name Rapamune and multiple drugmakers produce its generics. An off-label monthly supply of the drug can cost between around $150 for generics and about $1,000 for the brand-name product. Some are turning to digital pharmacies outside of the U.S. that sell the drug for much less.

A spokeswoman for Pfizer says the company doesn’t support off-label use of any of its medicines. The FDA says doctors are generally allowed to prescribe drugs for nonapproved uses if they think it makes sense. The agency doesn’t vouch for the safety or effectiveness of medications used off-label. 

Interest from longevity-seekers

Robin Young, an AI and biotech entrepreneur, started experimenting with various doses of rapamycin about two years ago in an attempt to determine what would work best for him. At the highest dose he tried, 20mg a week, he recalls getting several bad sinus infections.

Now, Mr. Young, who is based between Singapore and the Pacific Northwest, takes a lower dose every few weeks and avoids taking it at all when he’s traveling because of the added stress to his body. He worries about potential side effects such as high cholesterol but says he feels compelled by the potential benefits around cancer prevention. 

“I want to avoid these chronic diseases as much as possible,” says Mr. Young, 42, whose mother died of ovarian cancer when he was young. 

Dr. Bradley Rosen, a physician who runs a longevity-focused practice in Los Angeles, says rapamycin is the drug patients ask about most often. Dr. Kaeberlein, the aging researcher, says he gets “contacted once a week by someone who’s a CEO or a major partner in a venture-capital fund because they’re taking it.” 

Dr. Alan Green, who runs a longevity-focused practice in Queens, N.Y., says he has prescribed rapamycin off-label to more than 1,200 patients. The most common side effect he has observed is an increased risk of bacterial infections. He recommends patients not start taking the drug unless they have antibiotics on hand.  

AgelessRx, a telemedicine platform that prescribes longevity treatments, is running a randomized controlled trial with 150 participants to study how taking rapamycin affects visceral fat, or fat stored deep around the organs, which tends to increase as people age.

Krister Kauppi, a systems developer and biohacker in Gothenburg, Sweden, says he has taken rapamycin for longevity for roughly three months, even as questions remain about its long-term effectiveness and safety. 

“It’s still guesswork; we don’t know how well it will work on humans or not,” he says. “From a risk-benefit calculation perspective, I have decided that the benefits outweigh the risk.”

Write to Alex Janin at [email protected]