TY - JOUR
T1 - Rapamycin extends murine lifespan but has limited effects on aging
AU - Neff, Frauke
AU - Flores-Dominguez, Diana
AU - Ryan, Devon P.
AU - Horsch, Marion
AU - Schröder, Susanne
AU - Adler, Thure
AU - Afonso, Luciana Caminha
AU - Aguilar-Pimentel, Juan Antonio
AU - Becker, Lore
AU - Garrett, Lillian
AU - Hans, Wolfgang
AU - Hettich, Moritz M.
AU - Holtmeier, Richard
AU - Hölter, Sabine M.
AU - Moreth, Kristin
AU - Prehn, Cornelia
AU - Puk, Oliver
AU - Rácz, Ildikó
AU - Rathkolb, Birgit
AU - Rozman, Jan
AU - Naton, Beatrix
AU - Ordemann, Rainer
AU - Adamski, Jerzy
AU - Beckers, Johannes
AU - Bekeredjian, Raffi
AU - Busch, Dirk H.
AU - Ehninger, Gerhard
AU - Graw, Jochen
AU - Höfler, Heinz
AU - Klingenspor, Martin
AU - Klopstock, Thomas
AU - Ollert, Markus
AU - Stypmann, Jörg
AU - Wolf, Eckhard
AU - Wurst, Wolfgang
AU - Zimmer, Andreas
AU - Fuchs, Helmut
AU - Gailus-Durner, Valérie
AU - De Angelis, Martin Hrabe
AU - Ehninger, Dan
PY - 2013/8/1
Y1 - 2013/8/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84881247539&partnerID=8YFLogxK
U2 - 10.1172/JCI67674
DO - 10.1172/JCI67674
M3 - Article
C2 - 23863708
AN - SCOPUS:84881247539
SN - 0021-9738
VL - 123
SP - 3272
EP - 3291
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 8
ER -