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.

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Article and author information

Author details

  1. Alessandro Bitto

    Department of Pathology, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Takashi K Ito

    Department of Pathology, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Victor V Pineda

    Department of Pathology, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Nicolas J Letexier

    Department of Pathology, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Heather Z Huang

    Department of Pathology, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Elissa Sutlief

    Department of Pathology, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Herman Tung

    Department of Pathology, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Nicholas Vizzini

    Department of Pathology, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Belle Chen

    Department of Pathology, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Kaleb Smith

    Department of Pathology, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Daniel Meza

    Department of Pathology, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. Masanao Yajima

    Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  13. Richard P Beyer

    Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  14. Kathleen F Kerr

    Department of Biostatistics, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  15. Daniel J Davis

    Department of Veterinary Pathobiology, University of Missouri, Columbia, United States
    Competing interests
    The authors declare that no competing interests exist.
  16. Catherine H Gillespie

    Department of Veterinary Pathobiology, University of Missouri, Columbia, United States
    Competing interests
    The authors declare that no competing interests exist.
  17. Jessica M Snyder

    Department of Comparative Medicine, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  18. Piper M Treuting

    Department of Comparative Medicine, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  19. Matt Kaeberlein

    Department of Pathology, University of Washington, Seattle, United States
    For correspondence
    kaeber@uw.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1311-3421

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.

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.

Reviewing Editor

  1. Amy J Wagers, Harvard University, United States

Publication history

  1. Received: March 24, 2016
  2. Accepted: August 3, 2016
  3. Accepted Manuscript published: August 23, 2016 (version 1)
  4. 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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  1. Alessandro Bitto
  2. Takashi K Ito
  3. Victor V Pineda
  4. Nicolas J Letexier
  5. Heather Z Huang
  6. Elissa Sutlief
  7. Herman Tung
  8. Nicholas Vizzini
  9. Belle Chen
  10. Kaleb Smith
  11. Daniel Meza
  12. Masanao Yajima
  13. Richard P Beyer
  14. Kathleen F Kerr
  15. Daniel J Davis
  16. Catherine H Gillespie
  17. Jessica M Snyder
  18. Piper M Treuting
  19. Matt Kaeberlein
(2016)
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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