Transient rapamycin treatment robustly increases lifespan and healthspan in middle-aged mice

The FDA approved drug rapamycin increases lifespan in rodents1 and improves measures of age-related function in rodents2 and humans3; thus, rapamycin has promising translational potential as an intervention to promote both longevity and healthspan. Nevertheless, significant questions remain regarding the optimal dose, treatment regimen, efficacy, and safety of rapamycin administration in the context of healthy ageing4. Here we show that 3 months of rapamycin treatment is sufficient to increase life expectancy by more than 50% and improve measures of healthspan in middle-aged mice. Transient treatment with rapamycin is also associated with a remodelling of the microbiome, including dramatically increased prevalence of segmented filamentous bacteria in the small intestine. We also define a dose in female mice that does not extend lifespan. This higher dose of rapamycin is associated with a striking shift in cancer prevalence toward aggressive haematopoietic cancers and away from non-haematopoietic malignancies in females. These data demonstrate that a single short-term rapamycin treatment late in life can be effective at delaying ageing and suggest that a similar regimen may be applicable to promote healthy ageing in people.