title: Rapamycin extends life and health in C57BL/6 mice.
abstract: Target of rapamycin inhibition by rapamycin feeding has previously been shown to extend life in genetically heterogeneous mice. To examine whether it similarly affected mouse health, we fed encapsulated rapamycin or a control diet to C57BL/6Nia mice of both sexes starting at 19 months of age. We performed a range of health assessments 6 and 12 months later. Rapamycin feeding significantly reduced mTOR activity in most but not all tissues. It also reduced total and resting metabolic rate during the light (inactive) phase of the light:dark cycle in females only but had no effect on spontaneous activity or metabolism during the dark (active) phase of either sex. Males only had less fragmented sleep when fed rapamycin, whereas stride length and rotarod performance were improved in both sexes. Survival was also improved by this late-life rapamycin feeding, and some pathological lesions were delayed. We found no adverse health consequences associated with rapamycin treatment.
authors.affiliation: Barshop Institute, University of Texas Health Science Center at San Antonio, 15355 Lambda Drive, San Antonio, TX 78245-3207. fischerke@uthscsa.edu.
authors.forename: Yiqiang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Alex
authors.initials: A
authors.lastname: Bokov
authors.forename: John
authors.initials: J
authors.lastname: Gelfond
authors.forename: Vanessa
authors.initials: V
authors.lastname: Soto
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ikeno
authors.forename: Gene
authors.initials: G
authors.lastname: Hubbard
authors.forename: Vivian
authors.initials: V
authors.lastname: Diaz
authors.forename: Lauren
authors.initials: L
authors.lastname: Sloane
authors.forename: Keith
authors.initials: K
authors.lastname: Maslin
authors.forename: Stephen
authors.initials: S
authors.lastname: Treaster
authors.forename: Samantha
authors.initials: S
authors.lastname: Réndon
authors.forename: Holly
authors.initials: H
authors.lastname: van Remmen
authors.forename: Walter
authors.initials: W
authors.lastname: Ward
authors.forename: Martin
authors.initials: M
authors.lastname: Javors
authors.forename: Arlan
authors.initials: A
authors.lastname: Richardson
authors.forename: Steven N
authors.initials: SN
authors.lastname: Austad
authors.forename: Kathleen
authors.initials: K
authors.lastname: Fischer
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects; D001823:Body Composition / Q000187:drug effects*; D001921:Brain / Q000473:pathology; D004734:Energy Metabolism / Q000187:drug effects*; D005260:Female; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007668:Kidney / Q000473:pathology; D008099:Liver / Q000473:pathology; D008136:Longevity / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects*; D009206:Myocardium / Q000473:pathology; D045442:Rotarod Performance Test; D012737:Sex Factors; D020123:Sirolimus / Q000494:pharmacology*; D012890:Sleep / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000187:drug effects / Q000378:metabolism
chemical_list: D007166:Immunosuppressive Agents; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus
keywords: Aging; Health span; Rapamycin; Sex differences.