Transient rapamycin treatment can increase lifespan and healthspan in middle-aged mice
2016
Alessandro Bitto | Takashi K Ito | Victor V Pineda | Nicolas J LeTexier | Heather Z Huang | Elissa Sutlief | Herman Tung | Nicholas Vizzini | Belle Chen | Kaleb Smith | Daniel Meza | Masanao Yajima | Richard P Beyer | Kathleen F Kerr | Daniel J Davis | Catherine H Gillespie | Jessica M Snyder | Piper M Treuting | Matt Kaeberlein
The FDA approved drug rapamycin increases lifespan in rodents and delays age-related dysfunction in rodents and humans. Nevertheless, important questions remain regarding the optimal dose, duration, and mechanisms of action in the context of healthy aging. Here we show that 3 months of rapamycin treatment is sufficient to increase life expectancy by up to 60% and improve measures of healthspan in middle-aged mice. This transient treatment is also associated with a remodeling 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, but is associated with a striking shift in cancer prevalence toward aggressive hematopoietic cancers and away from non-hematopoietic malignancies. These data suggest that a short-term rapamycin treatment late in life has persistent effects that can robustly delay aging, influence cancer prevalence, and modulate the microbiome.
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