Scientists were shocked to find out that a promising longevity drug catching fire in the biohacking world may actually stunt the body’s ability to build and maintain muscle after working out.
Rapamycin, an FDA-approved prescription drug sometimes referred to as sirolimus, has made a splash in longevity-minded circles since a 2009 study found that it increased the lifespan of mice by up to 14 percent.
Animal studies have been optimistic about this transplant drug’s longevity potential. But new research suggests an unexpected trade-off: it may blunt the benefits of exercise, the best longevity intervention known to science.
Researchers in New Zealand recruited 40 sedentary adults in their 70s for a 13-week study. Half took a low dose of rapamycin once a week. The other half took a placebo pill. Everyone followed the same simple home exercise plan: stationary cycling and as many sit-to-stands as they could do in 30 seconds.
The results were not what the scientists expected. They had hoped that carefully timing the drug, taking it a full day after exercise, would allow people to get the longevity benefits of the medication without hindering their fitness gains.
Instead, the opposite happened. The people taking the placebo pill improved more than those taking rapamycin, which can cost as little as $1 per pill.
The placebo group improved by about three more chair stands than the rapamycin group. For a 70-year-old, those three reps can mean the difference between feeling strong and struggling to get off the toilet or out of a car and injuring themselves.
The problem comes down to one cellular switch called mTOR. Exercise flips it on to build muscle. Rapamycin flips it off. Even with careful timing, the drug stays in the body for several days, blocking the strength – and healthy longevity – gains someone would normally get from working out.
Rapamycin may slow aging by suppressing the growth switch mTOR to enhance cellular cleanup, but in doing so it also blocks the very same switch your muscles need to repair and grow stronger after exercise (stock)
Rapamycin was thrust onto the main stage by its vocal proponent, millionaire biohacker Bryan Johnson, who took the drug for five years before stopping in September 2024.
He cited ‘hefty side-effects’ including metabolic disruptions, intermittent skin and soft tissue infections, increased resting heart rate, and emerging evidence that the drug could speed up biological aging rather than slow it down.
University of Auckland researchers led by Dr Brad Stanfield, a general practitioner in Australia, split 70 sedentary seniors in half. One group took a low 6 mg dose of rapamycin weekly; the other took a placebo.
For 13 weeks, everyone followed the same home exercise routine, including stationary cycling and 30-second sit-to-stand tests three times per week.
The drug was taken 24 hours after the final weekly workout, timed to avoid the immediate post-exercise repair window of several hours when the body is actively rebuilding muscle tissue, making it stronger.
Both groups got fitter but the placebo group improved more. In the most complete analysis, the rapamycin group performed 3.4 fewer sit-to-stand repetitions than the placebo group.
Millionaire biohacker Bryan Johnson championed rapamycin for five years before quitting in September 2024, citing side effects and emerging evidence that the drug might accelerate aging rather than slow it
Those taking the placebo also tended to have stronger grip strength and reported better mental and physical health than the rapamycin group.
‘It was a surprise,’ Stanfield told the Washington Post, when he and his colleagues analyzed the subsequent data.
Stanfield said the findings, published in the Journal of Cachexia, Sarcopenia and Muscle, suggest rapamycin likely stayed in participants’ bodies long enough to block mTOR activity after exercise, preventing muscles from responding as strongly as they normally would.
The effects were not large, he said, but ‘the signal was definitely in the wrong direction.’
People taking rapamycin reported more side effects, including headaches, fatigue, and minor infections. One person in the drug group developed pneumonia and had to be hospitalized.
While the drug did not cause serious harm for most participants, the higher rate of side effects is a reminder that rapamycin is a powerful medication, not a vitamin or benign supplement.
Rapamycin, an FDA-approved immunosuppressant drug used to prevent organ rejection in transplantation, works by blocking an important cellular enzyme, mTOR, which acts as a master switch for growth.
When a person exercises, mTOR flips on, telling the muscles to repair and get stronger. With mTOR blocked, muscles cannot bulk up and may eventually atrophy.
Rapamycin backfired in this study because the drug is designed to turn mTOR off.
While beneficial in theory, rapamycin has a long half-life of 62 hours, meaning it lingers in the body for days. Even when participants took it a full day after exercising, it remained active during their next workout.
The chart compares sit-to-stand performance for the placebo group (black) and rapamycin group (gold) at the start and after 13 weeks of exercise. Both groups got stronger, but the placebo group gained more
Black triangles are placebo users; gold circles are rapamycin users. Most participants in both groups improved, landing above the faint dotted line, but the pattern favors placebo
Conversely, if mTOR stays flipped on, cells become so intent on growth and repair that they neglect the vital clean-up process called autophagy—the removal of damaged cell parts. Over time, that internal debris speeds up aging.
This is the uncomfortable trade-off that longevity experts and biohacking devotees must contend with: While rapamycin blocks muscle growth and repair, it also does something that longevity researchers find promising.
By suppressing mTOR, the drug keeps autophagy, the body’s cellular clean-up system, switched on for longer. That means damaged cell parts get cleared away instead of accumulating and causing trouble.
The problem, as this study shows, is that a wellness-minded individual may not be able to get that longevity benefit while also trying to build muscle from exercise. The drug does not know how to be selective. It just turns mTOR off everywhere, all the time.
Stanfield, who funded the study himself by mortgaging his home, selling vitamins and soliciting donations through social media, concluded that he does not believe people should be taking rapamycin for anything other than its prescribed purpose of preventing organ rejection.
His preferred longevity protocol? Hiking with his family.
