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

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

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.

Publication types

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

MeSH terms

  • Aging* / drug effects
  • Aging* / physiology
  • Animals
  • Drug Administration Schedule
  • Drug Chronotherapy
  • Female
  • Glucose Metabolism Disorders / etiology
  • Glucose Metabolism Disorders / prevention & control
  • Immune System / drug effects
  • Immunosuppressive Agents / administration & dosage
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / metabolism
  • Longevity* / drug effects
  • Longevity* / physiology
  • Mice
  • Mice, Inbred C57BL
  • Signal Transduction* / drug effects
  • Signal Transduction* / physiology
  • Sirolimus* / administration & dosage
  • Sirolimus* / adverse effects
  • Sirolimus* / metabolism
  • TOR Serine-Threonine Kinases / metabolism*
  • Treatment Outcome

Substances

  • Immunosuppressive Agents
  • TOR Serine-Threonine Kinases
  • Sirolimus