Open AccessRapamycin‐mediated lifespan increase in mice is dose and sex dependent and metabolically distinct from dietary restriction
Author(s) -
Miller Richard A.,
Harrison David E.,
Astle Clinton M.,
Fernandez Elizabeth,
Flurkey Kevin,
Han Melissa,
Javors Martin A.,
Li Xinna,
Nadon Nancy L.,
Nelson James F.,
Pletcher Scott,
Salmon Adam B.,
Sharp Zelton Dave,
Van Roekel Sabrina,
Winkleman Lynn,
Strong Randy
Publication year - 2014
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.12194
Subject(s) - biology , longevity , endocrinology , medicine , sexual dimorphism , endocrine system , mechanistic target of rapamycin , drug metabolism , pi3k/akt/mtor pathway , metabolism , physiology , genetics , hormone , apoptosis
Summary Rapamycin, an inhibitor of m TOR kinase, increased median lifespan of genetically heterogeneous mice by 23% (males) to 26% (females) when tested at a dose threefold higher than that used in our previous studies; maximal longevity was also increased in both sexes. Rapamycin increased lifespan more in females than in males at each dose evaluated, perhaps reflecting sexual dimorphism in blood levels of this drug. Some of the endocrine and metabolic changes seen in diet‐restricted mice are not seen in mice exposed to rapamycin, and the pattern of expression of hepatic genes involved in xenobiotic metabolism is also quite distinct in rapamycin‐treated and diet‐restricted mice, suggesting that these two interventions for extending mouse lifespan differ in many respects.