Authors: Wu JJ; Liu J; Chen EB; Wang JJ; Cao L; Narayan N; Fergusson MM; Rovira II; Allen M; Springer DA; Lago CU; Zhang S; Dubois W; Ward T; Decabo R; Gavrilova O; Mock B; Finkel T
Abstract: We analyzed aging parameters using a mechanistic target of rapamycin (mTOR) hypomorphic mouse model. Mice with two hypomorphic (mTOR(Delta/Delta)) alleles are viable but express mTOR at approximately 25% of wild-type levels. These animals demonstrate reduced mTORC1 and mTORC2 activity and exhibit an approximately 20% increase in median survival. While mTOR(Delta/Delta) mice are smaller than wild-type mice, these animals do not demonstrate any alterations in normalized food intake, glucose homeostasis, or metabolic rate. Consistent with their increased lifespan, mTOR(Delta/Delta) mice exhibited a reduction in a number of aging tissue biomarkers. Functional assessment suggested that, as mTOR(Delta/Delta) mice age, they exhibit a marked functional preservation in many, but not all, organ systems. Thus, in a mammalian model, while reducing mTOR expression markedly increases overall lifespan, it affects the age-dependent decline in tissue and organ function in a segmental fashion.
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Journal: Cell reports Volume: 4 Issue: 5 Pages: 913-20 Date: Sept. 3, 2013 PMID: 23994476 |
Wu JJ, Liu J, Chen EB, Wang JJ, Cao L, Narayan N, Fergusson MM, Rovira II, Allen M, Springer DA, Lago CU, Zhang S, Dubois W, Ward T, Decabo R, Gavrilova O, Mock B, Finkel T (2013) Increased Mammalian Lifespan and a Segmental and Tissue-Specific Slowing of Aging after Genetic Reduction of mTOR Expression. Cell reports 4: 913-20.
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