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Aging Cell. 2014 Jun;13(3):468-77. doi: 10.1111/acel.12194. Epub 2014 Feb 9.

Rapamycin-mediated lifespan increase in mice is dose and sex dependent and metabolically distinct from dietary restriction.

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1
Department of Pathology and Geriatrics Center, University of Michigan, Ann Arbor, MI, 48109, USA.

Abstract

Rapamycin, an inhibitor of mTOR 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.

KEYWORDS:

IGF-1; aging; caloric restriction; glucose; insulin; longevity; mTOR; mouse; rapamycin; xenobiotic metabolism

PMID:
24341993
PMCID:
PMC4032600
DOI:
10.1111/acel.12194
[Indexed for MEDLINE]
Free PMC Article
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