TY - JOUR
T1 - Increased mammalian lifespan and a segmental and tissue-specific slowing of aging after genetic reduction of mTOR expression
AU - Wu, J. Julie
AU - Liu, Jie
AU - Chen, EdmundB
AU - Wang, JenniferJ
AU - Cao, Liu
AU - Narayan, Nisha
AU - Fergusson, MarieM
AU - Rovira, IlsaI
AU - Allen, Michele
AU - Springer, DanielleA
AU - Lago, CoryU
AU - Zhang, Shuling
AU - DuBois, Wendy
AU - Ward, Theresa
AU - deCabo, Rafael
AU - Gavrilova, Oksana
AU - Mock, Beverly
AU - Finkel, Toren
PY - 2013/5/12
Y1 - 2013/5/12
N2 - We analyzed aging parameters using a mechanistic target of rapamycin (mTOR) hypomorphic mouse model. Mice with two hypomorphic (mTORδ/δ) 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 mTORδ/δ 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, mTORδ/δ mice exhibited a reduction in anumber of aging tissue biomarkers. Functional assessment suggested that, as mTORδ/δ 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
AB - We analyzed aging parameters using a mechanistic target of rapamycin (mTOR) hypomorphic mouse model. Mice with two hypomorphic (mTORδ/δ) 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 mTORδ/δ 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, mTORδ/δ mice exhibited a reduction in anumber of aging tissue biomarkers. Functional assessment suggested that, as mTORδ/δ 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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U2 - 10.1016/j.celrep.2013.07.030
DO - 10.1016/j.celrep.2013.07.030
M3 - Article
C2 - 23994476
AN - SCOPUS:84884150826
SN - 2211-1247
VL - 4
SP - 913
EP - 920
JO - Cell Reports
JF - Cell Reports
IS - 5
ER -