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

Aging Cell

Richard A. Miller⁸  David E. Harrison⁵  Clinton M. Astle⁵  Elizabeth Fernandez⁷  Kevin Flurkey⁵  Melissa Han⁸  Martin A. Javors⁶  Xinna Li⁸  Nancy L. Nadon⁴  James F. Nelson²  Scott Pletcher¹  Adam B. Salmon³  Zelton Dave Sharp³  Sabrina Van Roekel⁸  Lynn Winkleman⁸ 

[1]Department of Molecular and Integrative Physiology and Geriatrics Center, University of Michigan, Ann Arbor, MI, USA

[2]Department of Physiology and Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA

[3]Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center San Antonio, San Antonio, TX, USA

[4]Division of Aging Biology, National Institute on Aging, Bethesda, MD, USA

[5]The Jackson Laboratory, Bar Harbor, ME, USA

[6]Department of Psychiatry, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA

[7]Geriatric Research, Education and Clinical Center and Research Service, South Texas Veterans Health Care System, San Antonio, TX, USA

[8]Department of Pathology and Geriatrics Center, University of Michigan, Ann Arbor, MI, USA

关键词: aging;    caloric restriction;    glucose;    IGF‐1;    insulin;    longevity;    mouse;    mTOR;    rapamycin;    xenobiotic metabolism;   

DOI  :  10.1111/acel.12194

来源: Wiley

【 摘 要 】

Summary

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.

【 授权许可】

CC BY   
© 2014 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

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