Increased mammalian lifespan and a segmental and tissue-specific slowing of aging after genetic reduction of mTOR expression.

ABSTRACT: We analyzed aging parameters using a mechanistic target of rapamycin (mTOR) hypomorphic mouse model. Mice with two hypomorphic (mTOR(?/?)) 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(?/?) 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(?/?) mice exhibited a reduction in a number of aging tissue biomarkers. Functional assessment suggested that, as mTOR(?/?) 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.

SUBMITTER: Wu JJ 

PROVIDER: S-EPMC3784301 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature