Bitto, AlessandroIto, Takashi K.Pineda, Victor V.LeTexier, Nicolas J.Huang, Heather Z.Sutlief, ElissaTung, HermanVizzini, NicholasChen, BelleSmith, KalebMeza, DanielYajima, MasanaoBeyer, Richard P.Kerr, Kathleen F.Davis, Daniel J.Gillespie, Catherine H.Snyder, Jessica M.Treuting, Piper M.Kaeberlein, Matt2018-03-292018-03-292016-08-03Alessandro 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. "Transient rapamycin treatment can increase lifespan and healthspan in middle-aged mice.." Elife, Volume 5,2050-084Xhttps://hdl.handle.net/2144/27895The 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.Copyright 2016 Bitto et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.http://creativecommons.org/licenses/by/4.0/AgingCancerCancer biologyDevelopmental biologyHealthspanLongevitymTORMicrobiomeMouseStem cellsAnimalsAnti-bacterial agentsAntibiotics, antineoplasticGastrointestinal microbiomeMiceNeoplasmsSirolimusAnimalsTransient rapamycin treatment can increase lifespan and healthspan in middle-aged miceArticle10.7554/eLife.16351