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

First Author  Wu JJ Year  2013
Journal  Cell Rep Volume  4
Issue  5 Pages  913-20
PubMed ID  23994476 Mgi Jnum  J:202846
Mgi Id  MGI:5522608 Doi  10.1016/j.celrep.2013.07.030
Citation  Wu JJ, et al. (2013) Increased mammalian lifespan and a segmental and tissue-specific slowing of aging after genetic reduction of mTOR expression. Cell Rep 4(5):913-20
abstractText  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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