期刊
CELL REPORTS
卷 4, 期 5, 页码 913-920出版社
CELL PRESS
DOI: 10.1016/j.celrep.2013.07.030
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资金
- NIH
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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