By understanding rapamycin, researchers on the path to extending lifespan

Eat less, live longer. Researchers have long known that one of the keys to a longer, healthier life is simply to eat less. But is it possible to mimic the effects of caloric restriction without actually changing our diet? Researchers at Whitehead Institute think so, by harnessing the power of the drug rapamycin.

Rapamycin is currently widely used for immunosuppression in organ transplantations and is already known to mimic the effects of caloric restriction and increase lifespan. But there’s a (big) caveat: it also impairs glucose tolerance and insulin sensitivity, two characteristics of diabetes. So to better understand rapamycin’s benefits and risks, researchers from the lab of Whitehead Institute Member David Sabatini are investigating precisely how rapamycin is behaving at the cellular level.

Dr. Dudley Lamming, a postdoctoral fellow in Dr. Sabatini’s lab, made a key discovery showing that rapamycin is targeting the protein complex mTORC2. Photo credit: Mark Bushy

“We know that despite its adverse effects, rapamycin still prolongs lifespan, so there’s a potential that we could make it better by just having lifespan affected and not induce the adverse effects,” says Dr. Sabatini.

His research recently yielded a remarkable discovery—while rapamycin was thought to primarily target the protein complex mTORC1, it’s actually targeting two protein complexes, mTORC1 and mTORC2. These findings suggest that a drug capable of targeting only mTORC1 could potentially increase lifespan without causing the negative metabolic effects.

Dr. Sabatini and his collaborators are now working to identify a drug capable of targeting only mTORC1. If such a drug candidate were identified, it would be a first-of-its-kind therapy, capable of extending lifespan and perhaps ameliorating aging-related diseases.