Increased Mammalian Lifespan and a Segmental and Tissue-Specific Slowing of Aging after Genetic Reduction of mTOR Expression.
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 Year: 2013 Journal: Cell reports 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. Reference
Created on Oct. 25, 2013, 10:23 p.m. Not linked Integrated: False