title: Rapamycin extends murine lifespan but has limited effects on aging.
abstract: Aging is a major risk factor for a large number of disorders and functional impairments. Therapeutic targeting of the aging process may therefore represent an innovative strategy in the quest for novel and broadly effective treatments against age-related diseases. The recent report of lifespan extension in mice treated with the FDA-approved mTOR inhibitor rapamycin represented the first demonstration of pharmacological extension of maximal lifespan in mammals. Longevity effects of rapamycin may, however, be due to rapamycin's effects on specific life-limiting pathologies, such as cancers, and it remains unclear if this compound actually slows the rate of aging in mammals. Here, we present results from a comprehensive, large-scale assessment of a wide range of structural and functional aging phenotypes, which we performed to determine whether rapamycin slows the rate of aging in male C57BL/6J mice. While rapamycin did extend lifespan, it ameliorated few studied aging phenotypes. A subset of aging traits appeared to be rescued by rapamycin. Rapamycin, however, had similar effects on many of these traits in young animals, indicating that these effects were not due to a modulation of aging, but rather related to aging-independent drug effects. Therefore, our data largely dissociate rapamycin's longevity effects from effects on aging itself.
authors.affiliation: Institute of Pathology, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: Frauke
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authors.lastname: Flores-Dominguez
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authors.lastname: Horsch
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authors.lastname: Schröder
authors.forename: Thure
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authors.forename: Ildikó
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authors.forename: Birgit
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authors.lastname: Rathkolb
authors.forename: Jan
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authors.lastname: Rozman
authors.forename: Beatrix
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authors.lastname: Naton
authors.forename: Rainer
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authors.lastname: Ordemann
authors.forename: Jerzy
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authors.lastname: Adamski
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authors.lastname: Beckers
authors.forename: Raffi
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authors.lastname: Bekeredjian
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authors.lastname: Ehninger
authors.forename: Jochen
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authors.lastname: Graw
authors.forename: Heinz
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authors.lastname: Höfler
authors.forename: Martin
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authors.lastname: Klingenspor
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authors.lastname: Klopstock
authors.forename: Markus
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authors.lastname: Ollert
authors.forename: Jörg
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authors.lastname: Stypmann
authors.forename: Eckhard
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authors.lastname: Wolf
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wurst
authors.forename: Andreas
authors.initials: A
authors.lastname: Zimmer
authors.forename: Helmut
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authors.lastname: Fuchs
authors.forename: Valérie
authors.initials: V
authors.lastname: Gailus-Durner
authors.forename: Martin
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authors.lastname: Hrabe de Angelis
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authors.lastname: Ehninger
mesh_terms: D000375:Aging / Q000187:drug effects*; D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D006099:Granuloma / Q000517:prevention & control; D007136:Immunoglobulins / Q000097:blood; D007958:Leukocyte Count; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008103:Liver Cirrhosis / Q000517:prevention & control; D008136:Longevity / Q000187:drug effects*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D053580:Muscle Strength / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D010641:Phenotype; D010976:Platelet Count; D011597:Psychomotor Performance / Q000187:drug effects; D020123:Sirolimus / Q000494:pharmacology*; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D013961:Thyroid Gland / Q000187:drug effects / Q000473:pathology
chemical_list: D007136:Immunoglobulins; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus