Affiliation: | 1. The Jackson Laboratory, , Bar Harbor, ME, 04609 USA;2. Geriatric Research, Education and Clinical Center and Research Service, South Texas Veterans Health Care System, , San Antonio, TX, 78229 USA;3. Department of Pathology and Geriatrics Center, University of Michigan, , Ann Arbor, MI, 48109 USA;4. Department of Psychiatry, The University of Texas Health Science Center at San Antonio, , San Antonio, TX, 78229 USA;5. Division of Aging Biology, National Institute on Aging, , Bethesda, MD, 20892 USA;6. Department of Physiology and Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, , San Antonio, TX, 78229 USA;7. Department of Molecular and Integrative Physiology and Geriatrics Center, University of Michigan, , Ann Arbor, MI, 48109 USA;8. Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center San Antonio, , San Antonio, TX, 78245 USA;9. Department of Molecular Medicine, University of Texas Health Science Center San Antonio, , San Antonio, TX, 78245 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. |