title: Health Effects of Long-Term Rapamycin Treatment: The Impact on Mouse Health of Enteric Rapamycin Treatment from Four Months of Age throughout Life.
abstract: Rapamycin, an mTOR inhibitor, has been shown to extend lifespan in a range of model organisms. It has been reported to extend lifespan in multiple strains of mice, administered chronically or acutely early or late in life. The ability of rapamycin to extend health (healthspan) as opposed to life is less well documented. To assess the effects chronic rapamycin treatment on healthspan, enteric rapamycin was given to male and female C57BL/6J mice starting at 4 months of age and continued throughout life. Repeated, longitudinal assessments of health in individual animals were made starting at 16 months of age (=12 months of treatment) until death. A number of health parameters were improved (female grip strength, female body mass and reduced sleep fragmentation in both sexes), others showed no significant difference, while at least one (male rotarod performance) was negatively affected. Rapamycin treatment affected many measures of health in a highly sex-specific manner. While sex-specific phenotypic effects of rapamycin treatment have been widely reported, in this study we document sex differences in the direction of phenotypic change. Rapamycin-fed males and females were both significantly different from controls; however the differences were in the opposite direction in measures of body mass, percent fat and resting metabolic rate, a pattern not previously reported.
authors.affiliation: Barshop Institute for Longevity & Aging Studies, University of Texas Health Science Center San Antonio, San Antonio, Texas, United States of America; Department of Physiology, University of Texas Health Science Center San Antonio, San Antonio, Texas, United States of America.
authors.forename: Kathleen E
authors.initials: KE
authors.lastname: Fischer
authors.affiliation: Department of Epidemiology & Biostatistics, University of Texas Health Science Center San Antonio, San Antonio, Texas, United States of America.
authors.forename: Jonathan A L
authors.initials: JA
authors.lastname: Gelfond
authors.affiliation: Barshop Institute for Longevity & Aging Studies, University of Texas Health Science Center San Antonio, San Antonio, Texas, United States of America.
authors.forename: Vanessa Y
authors.initials: VY
authors.lastname: Soto
authors.affiliation: Departments of Aging and Geriatric Research, University of Florida, Gainesville, Florida, United States of America.
authors.forename: Chul
authors.initials: C
authors.lastname: Han
authors.affiliation: Departments of Aging and Geriatric Research, University of Florida, Gainesville, Florida, United States of America.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Someya
authors.affiliation: Barshop Institute for Longevity & Aging Studies, University of Texas Health Science Center San Antonio, San Antonio, Texas, United States of America; Department of Cellular & Structural Biology, University of Texas Health Science Center San Antonio, San Antonio, Texas, United States of America.
authors.forename: Arlan
authors.initials: A
authors.lastname: Richardson
authors.affiliation: Barshop Institute for Longevity & Aging Studies, University of Texas Health Science Center San Antonio, San Antonio, Texas, United States of America; Department of Cellular & Structural Biology, University of Texas Health Science Center San Antonio, San Antonio, Texas, United States of America.
authors.forename: Steven N
authors.initials: SN
authors.lastname: Austad
mesh_terms: D000375:Aging; D000818:Animals; D005260:Female; D008136:Longevity / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012737:Sex Factors; D020123:Sirolimus / Q000494:pharmacology*; D012890:Sleep / Q000187:drug effects
chemical_list: D020123:Sirolimus