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Elife. 2016 Aug 23;5. pii: e16351. doi: 10.7554/eLife.16351.

Transient rapamycin treatment can increase lifespan and healthspan in middle-aged mice.

Author information

1
Department of Pathology, University of Washington, Seattle, United States.
2
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States.
3
Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, United States.
4
Department of Biostatistics, University of Washington, Seattle, United States.
5
Department of Veterinary Pathobiology, University of Missouri, Columbia, United States.
6
Department of Comparative Medicine, University of Washington, Seattle, 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.

KEYWORDS:

aging; cancer; cancer biology; developmental biology; healthspan; longevity; mTOR; microbiome; mouse; stem cells

PMID:
27549339
PMCID:
PMC4996648
DOI:
10.7554/eLife.16351
[Indexed for MEDLINE]
Free PMC Article

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