title: Rapamycin Versus Intermittent Feeding: Dissociable Effects on Physiological and Behavioral Outcomes When Initiated Early and Late in Life.
abstract: Rapamycin, an inhibitor of the mammalian target of rapamycin pathway, has been shown to increase mammalian life span; less is known concerning its effect on healthspan. The primary aim of this study was to examine rapamycin's role in the alteration of several physiological and behavioral outcomes compared with the healthspan-inducing effects of intermittent feeding (IF), another life-span-enhancing intervention. Male Fisher 344 × Brown Norway rats (6 and 25 months of age) were treated with rapamycin or IF for 5 weeks. IF and rapamycin reduced food consumption and body weight. Rapamycin increased relative lean mass and decreased fat mass. IF failed to alter fat mass but lowered relative lean mass. Behaviorally, rapamycin resulted in high activity levels in old animals, IF increased levels of "anxiety" for both ages, and grip strength was not significantly altered by either treatment. Rapamycin, not IF, decreased circulating leptin in older animals to the level of young animals. Glucose levels were unchanged with age or treatment. Hypothalamic AMPK and pAMPK levels decreased in both older treated groups. This pattern of results suggests that rapamycin has more selective and healthspan-inducing effects when initiated late in life.
authors.affiliation: Department of Aging and Geriatric Research, cartercs@ufl.edu.
authors.forename: Christy S
authors.initials: CS
authors.lastname: Carter
authors.affiliation: Department of Aging and Geriatric Research.
authors.forename: Dallas
authors.initials: D
authors.lastname: Khamiss
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, and.
authors.forename: Michael
authors.initials: M
authors.lastname: Matheny
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, and.
authors.forename: Hale Z
authors.initials: HZ
authors.lastname: Toklu
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, and.
authors.forename: Nataliya
authors.initials: N
authors.lastname: Kirichenko
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, and.
authors.forename: Kevin Y E
authors.initials: KY
authors.lastname: Strehler
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, and Department of Veterans Affairs Medical Center, Gainesville, Florida.
authors.forename: Nihal
authors.initials: N
authors.lastname: Tümer
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, and.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Scarpace
authors.affiliation: Department of Psychiatry, University of Florida College of Medicine, Gainesville.
authors.forename: Drake
authors.initials: D
authors.lastname: Morgan
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000375:Aging / Q000187:drug effects / Q000502:physiology / Q000523:psychology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D005248:Feeding Methods / Q000523:psychology; D007166:Immunosuppressive Agents / Q000378:metabolism / Q000494:pharmacology; D020738:Leptin / Q000378:metabolism; D008136:Longevity / Q000187:drug effects / Q000502:physiology; D008297:Male; D010805:Physical Conditioning, Animal / Q000379:methods; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D020123:Sirolimus / Q000378:metabolism / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D020738:Leptin; D058570:TOR Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; D020123:Sirolimus
keywords: Calorie restriction; Healthspan; Leptin; Life span; Physical function; mTOR; p70S6K