title: Transient rapamycin treatment can increase lifespan and healthspan in middle-aged mice.
abstract: 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.
authors.affiliation: Department of Pathology, University of Washington, Seattle, United States.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Bitto
authors.affiliation: Department of Pathology, University of Washington, Seattle, United States.
authors.forename: Takashi K
authors.initials: TK
authors.lastname: Ito
authors.affiliation: Department of Pathology, University of Washington, Seattle, United States.
authors.forename: Victor V
authors.initials: VV
authors.lastname: Pineda
authors.affiliation: Department of Pathology, University of Washington, Seattle, United States.
authors.forename: Nicolas J
authors.initials: NJ
authors.lastname: LeTexier
authors.affiliation: Department of Pathology, University of Washington, Seattle, United States.
authors.forename: Heather Z
authors.initials: HZ
authors.lastname: Huang
authors.affiliation: Department of Pathology, University of Washington, Seattle, United States.
authors.forename: Elissa
authors.initials: E
authors.lastname: Sutlief
authors.affiliation: Department of Pathology, University of Washington, Seattle, United States.
authors.forename: Herman
authors.initials: H
authors.lastname: Tung
authors.affiliation: Department of Pathology, University of Washington, Seattle, United States.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Vizzini
authors.affiliation: Department of Pathology, University of Washington, Seattle, United States.
authors.forename: Belle
authors.initials: B
authors.lastname: Chen
authors.affiliation: Department of Pathology, University of Washington, Seattle, United States.
authors.forename: Kaleb
authors.initials: K
authors.lastname: Smith
authors.affiliation: Department of Pathology, University of Washington, Seattle, United States.
authors.forename: Daniel
authors.initials: D
authors.lastname: Meza
authors.affiliation: Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States.
authors.forename: Masanao
authors.initials: M
authors.lastname: Yajima
authors.affiliation: Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, United States.
authors.forename: Richard P
authors.initials: RP
authors.lastname: Beyer
authors.affiliation: Department of Biostatistics, University of Washington, Seattle, United States.
authors.forename: Kathleen F
authors.initials: KF
authors.lastname: Kerr
authors.affiliation: Department of Veterinary Pathobiology, University of Missouri, Columbia, United States.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Davis
authors.affiliation: Department of Veterinary Pathobiology, University of Missouri, Columbia, United States.
authors.forename: Catherine H
authors.initials: CH
authors.lastname: Gillespie
authors.affiliation: Department of Comparative Medicine, University of Washington, Seattle, United States.
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Snyder
authors.affiliation: Department of Comparative Medicine, University of Washington, Seattle, United States.
authors.forename: Piper M
authors.initials: PM
authors.lastname: Treuting
authors.affiliation: Department of Pathology, University of Washington, Seattle, United States.
authors.forename: Matt
authors.identifier: 0000-0002-1311-3421
authors.initials: M
authors.lastname: Kaeberlein
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage*; D000069196:Gastrointestinal Microbiome / Q000187:drug effects*; D008136:Longevity / Q000187:drug effects*; D051379:Mice; D009369:Neoplasms / Q000517:prevention & control*; D020123:Sirolimus / Q000008:administration & dosage*
chemical_list: D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic; D020123:Sirolimus
keywords: aging; cancer; cancer biology; developmental biology; healthspan; longevity; mTOR; microbiome; mouse; stem cells