Transient rapamycin treatment can increase lifespan and healthspan in middle-aged mice
- University of Washington, United States
- Fred Hutchinson Cancer Research Center, United States
- University of Missouri, United States
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.
Data availability
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Transient rapamycin treatment robustly increases lifespan and healthspan in middle-aged micePublicly available at the EBI European Nucleotide Archive (accession no: ERP014805).
Article and author information
Author details
Funding
Samsung
- Matt Kaeberlein
National Institute on Aging (P30AG013280)
- Matt Kaeberlein
University of Washington
- Daniel J Davis
National Institute on Aging (T32AG000057)
- Alessandro Bitto
Japan Society for the Promotion of Science
- Takashi K Ito
Uehara Memorial Foundation
- Takashi K Ito
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Amy J Wagers, Harvard University, United States
Ethics
Animal experimentation: This study was performed in accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (#4359-01) of the University of Washington.
Version history
- Received: March 24, 2016
- Accepted: August 3, 2016
- Accepted Manuscript published: August 23, 2016 (version 1)
- Version of Record published: August 24, 2016 (version 2)
Copyright
© 2016, Bitto et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Transient rapamycin treatment can increase lifespan and healthspan in middle-aged mice
eLife 5:e16351.
https://doi.org/10.7554/eLife.16351
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