Rapamycin reduced exercise gains in older adults, NZ trial

A 13-week clinical trial in Auckland tested whether intermittent rapamycin (sirolimus) added to an exercise program would improve function in older adults. Forty sedentary volunteers aged 65 to 85 were enrolled. Participants were randomly assigned to take a once-weekly 6 mg dose of rapamycin or matching placebo while following the same supervised exercise program.

Researchers measured walking distance, muscle strength and chair-stand repetitions to assess physical function. Participants who received placebo showed larger improvements across those measures. The placebo group walked farther in functional tests, gained more strength and completed about 3.4 more chair-stand repetitions on average than the rapamycin group.

The percentage of participants reporting at least one side effect was roughly equal in both groups, about 85 percent. However, the rapamycin group experienced a higher total number of adverse events: 99 events versus 63 in the placebo group. One person who received a single dose of rapamycin was hospitalized with pneumonia.

Dr. Brad Stanfield, the trial’s lead investigator, offered a pharmacokinetic explanation for the results. He and the research team noted rapamycin has an approximate half-life of 62 hours, and active drug levels persisted into later training sessions. They suggested those lingering levels could have partially blocked mTOR signaling at times when muscles needed it for growth and repair. ‘Rapamycin didn’t help. Instead, it may have made things worse,’ Stanfield wrote in a public summary of the trial.

The study was co-funded by VitaDAO, a decentralized science community. The research team described the funding model as a way to support early clinical testing of ideas emerging from basic aging research. Technology and crypto-linked donors have recently increased their support for longevity studies.

The trial did not measure lifespan. Animal research has shown large lifespan gains in rodents after months of rapamycin treatment; a review on PubMed Central reports increases of up to about 60 percent in some rodent studies. The Auckland trial was designed to test a practical application of rapamycin for preserving muscle function in older adults.

The investigators said further research is needed to evaluate different doses, timing and safety if rapamycin is to be considered as an adjunct to exercise in older people.