title: Short-term treatment with rapamycin and dietary restriction have overlapping and distinctive effects in young mice.
abstract: Because rapamycin, an inhibitor of the nutrient sensor mammalian target of rapamycin, and dietary restriction both increase life span of mice, it has been hypothesized that they act through similar mechanisms. To test this hypothesis, we compared various biological parameters in dietary restriction mice (40% food restriction) and mice fed rapamycin (14 ppm). Both treatments led to a significant reduction in mammalian target of rapamycin signaling and a corresponding increase in autophagy. However, we observed striking differences in fat mass, insulin sensitivity, and expression of cell cycle and sirtuin genes in mice fed rapamycin compared with dietary restriction. Thus, although both treatments lead to significant downregulation of mammalian target of rapamycin signaling, these two manipulations have quite different effects on other physiological functions suggesting that they might increase life span through a common pathway as well as pathways that are altered differently by dietary restriction and rapamycin.
authors.affiliation: Department of Cellular and Structural Biology, The University of Texas Health Science Center at San Antonio, Texas, USA.
authors.forename: Wilson C
authors.initials: WC
authors.lastname: Fok
authors.forename: Yiqiang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Adam B
authors.initials: AB
authors.lastname: Salmon
authors.forename: Arunabh
authors.initials: A
authors.lastname: Bhattacharya
authors.forename: Rakesh
authors.initials: R
authors.lastname: Gunda
authors.forename: Dean
authors.initials: D
authors.lastname: Jones
authors.forename: Walter
authors.initials: W
authors.lastname: Ward
authors.forename: Kathleen
authors.initials: K
authors.lastname: Fisher
authors.forename: Arlan
authors.initials: A
authors.lastname: Richardson
authors.forename: Viviana I
authors.initials: VI
authors.lastname: Pérez
mesh_terms: D000375:Aging / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001343:Autophagy / Q000187:drug effects; D031204:Caloric Restriction; D015870:Gene Expression / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D007333:Insulin Resistance; D008136:Longevity / Q000187:drug effects* / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010084:Oxidation-Reduction; D015398:Signal Transduction / Q000187:drug effects; D020123:Sirolimus / Q000008:administration & dosage*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases; D005978:Glutathione; D020123:Sirolimus