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J Gerontol A Biol Sci Med Sci. 2016 Jul;71(7):876-81. doi: 10.1093/gerona/glw064. Epub 2016 Apr 18.

Intermittent Administration of Rapamycin Extends the Life Span of Female C57BL/6J Mice.

Author information

1
Department of Medicine, University of Wisconsin-Madison. William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin.
2
Department of Medicine, University of Wisconsin-Madison. William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin. Endocrinology and Reproductive Physiology Graduate Training Program, University of Wisconsin-Madison.
3
Department of Medicine, University of Wisconsin-Madison. William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin. Endocrinology and Reproductive Physiology Graduate Training Program, University of Wisconsin-Madison. dlamming@medicine.wisc.edu.

Abstract

Inhibition of the mTOR (mechanistic target of rapamycin) signaling pathway by the FDA-approved drug rapamycin promotes life span in numerous model organisms and delays age-related disease in mice. However, the utilization of rapamycin as a therapy for age-related diseases will likely prove challenging due to the serious metabolic and immunological side effects of rapamycin in humans. We recently identified an intermittent rapamycin treatment regimen-2mg/kg administered every 5 days-with a reduced impact on glucose homeostasis and the immune system as compared with chronic treatment; however, the ability of this regimen to extend life span has not been determined. Here, we report for the first time that an intermittent rapamycin treatment regimen starting as late as 20 months of age can extend the life span of female C57BL/6J mice. Our work demonstrates that the anti-aging potential of rapamycin is separable from many of its negative side effects and suggests that carefully designed dosing regimens may permit the safer use of rapamycin and its analogs for the treatment of age-related diseases in humans.

KEYWORDS:

Anti-aging; Life span; Mice; Rapamycin; mTOR

PMID:
27091134
PMCID:
PMC4906329
DOI:
10.1093/gerona/glw064
[Indexed for MEDLINE]
Free PMC Article

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