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Neff, F. ; Flores-Dominguez, D.* ; Ryan, D.P.* ; Horsch, M. ; Schröder, S.* ; Adler, T. ; Afonso, L.C. ; Aguilar-Pimentel, J.A. ; Becker, L. ; Garrett, L. ; Hans, W. ; Hettich, M.M.* ; Holtmeier, R.* ; Hölter, S.M. ; Moreth, K. ; Prehn, C. ; Puk, O. ; Rácz, I.* ; Rathkolb, B. ; Rozman, J. ; Naton, B. ; Ordemann, R.* ; Adamski, J. ; Beckers, J. ; Bekeredjian, R.* ; Busch, D.H.* ; Ehninger, G.* ; Graw, J. ; Höfler, H. ; Klingenspor, M.* ; Klopstock, T.* ; Ollert, M.* ; Stypmann, J.* ; Wolf, E.* ; Wurst, W. ; Zimmer, A.* ; Fuchs, H. ; Gailus-Durner, V. ; Hrabě de Angelis, M. ; Ehniger, D.*

Rapamycin extends murine lifespan but has limited effects on aging.

J. Clin. Invest. 123, 3272-3291 (2013)
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Open Access Gold
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Genetically Heterogeneous Mice ; Mammalian Target ; Tor Pathway ; Insulin-resistance ; Signaling Pathway ; Mtor Inhibition ; Rats ; Age ; System ; Tissue
Sprache englisch
Veröffentlichungsjahr 2013
HGF-Berichtsjahr 2013
ISSN (print) / ISBN 0021-9738
e-ISSN 1558-8238
Zeitschrift Journal of Clinical Investigation
Quellenangaben Band: 123, Heft: 3, Seiten: 3272-3291 Artikelnummer: , Supplement: ,
Verlag American Society of Clinical Investigation
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Pathology (PATH)
Institute of Experimental Genetics (IEG)
Institute of Developmental Genetics (IDG)
Molekulare Endokrinologie und Metabolismus (MEM)
POF Topic(s) 30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
30201 - Metabolic Health
30204 - Cell Programming and Repair
90000 - German Center for Diabetes Research
Forschungsfeld(er) Enabling and Novel Technologies
Genetics and Epidemiology
PSP-Element(e) G-500300-001
G-500600-001
G-500600-003
G-500600-004
G-500500-001
G-505600-001
G-500500-002
G-501900-061
G-501900-063
PubMed ID 23863708
DOI 10.1172/JCI67674
WOS ID WOS:000322750500012
Scopus ID 84881247539
Erfassungsdatum 2013-07-26
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