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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Anti-Bacterial Agents / administration & dosage*
  • Antibiotics, Antineoplastic / administration & dosage*
  • Gastrointestinal Microbiome / drug effects*
  • Longevity / drug effects*
  • Mice
  • Neoplasms / prevention & control*
  • Sirolimus / administration & dosage*

Substances

  • Anti-Bacterial Agents
  • Antibiotics, Antineoplastic
  • Sirolimus