title: Intermittent Administration of Rapamycin Extends the Life Span of Female C57BL/6J Mice.
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.
authors.affiliation: Department of Medicine, University of Wisconsin-Madison. William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin.
authors.forename: Sebastian I
authors.initials: SI
authors.lastname: Arriola Apelo
authors.affiliation: Department of Medicine, University of Wisconsin-Madison. William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin.
authors.forename: Cassidy P
authors.initials: CP
authors.lastname: Pumper
authors.affiliation: Department of Medicine, University of Wisconsin-Madison. William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin.
authors.forename: Emma L
authors.initials: EL
authors.lastname: Baar
authors.affiliation: 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.
authors.forename: Nicole E
authors.initials: NE
authors.lastname: Cummings
authors.affiliation: 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.
authors.forename: Dudley W
authors.initials: DW
authors.lastname: Lamming
mesh_terms: D000375:Aging / Q000187:drug effects / Q000502:physiology; D000818:Animals; D004334:Drug Administration Schedule; D055870:Drug Chronotherapy; D005260:Female; D044882:Glucose Metabolism Disorders / Q000209:etiology / Q000517:prevention & control; D007107:Immune System / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism; D008136:Longevity / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D020123:Sirolimus / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus
keywords: Anti-aging; Life span; Mice; Rapamycin; mTOR