These three authors contributed equally to this study.
Rapamycin-mediated lifespan increase in mice is dose and sex dependent and metabolically distinct from dietary restriction
Article first published online: 9 FEB 2014
© 2014 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Volume 13, Issue 3, pages 468–477, June 2014
How to Cite
Miller, R. A., Harrison, D. E., Astle, C. M., Fernandez, E., Flurkey, K., Han, M., Javors, M. A., Li, X., Nadon, N. L., Nelson, J. F., Pletcher, S., Salmon, A. B., Sharp, Z. D., Van Roekel, S., Winkleman, L. and Strong, R. (2014), Rapamycin-mediated lifespan increase in mice is dose and sex dependent and metabolically distinct from dietary restriction. Aging Cell, 13: 468–477. doi: 10.1111/acel.12194
- Issue published online: 23 MAY 2014
- Article first published online: 9 FEB 2014
- Accepted manuscript online: 17 DEC 2013 05:54AM EST
- Manuscript Accepted: 7 DEC 2013
- NIH. Grant Numbers: AG022303, AG031736, AG022307, AG13319, AG022308, CA034196
- caloric restriction;
- xenobiotic metabolism
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.