Cell Reports
(Sep 2013)
Increased Mammalian Lifespan and a Segmental and Tissue-Specific Slowing of Aging after Genetic Reduction of mTOR Expression
J. Julie Wu,
Jie Liu,
Edmund B. Chen,
Jennifer J. Wang,
Liu Cao,
Nisha Narayan,
Marie M. Fergusson,
Ilsa I. Rovira,
Michele Allen,
Danielle A. Springer,
Cory U. Lago,
Shuling Zhang,
Wendy DuBois,
Theresa Ward,
Rafael deCabo,
Oksana Gavrilova,
Beverly Mock,
Toren Finkel
Affiliations
J. Julie Wu
Center for Molecular Medicine, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
Jie Liu
Center for Molecular Medicine, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
Edmund B. Chen
Center for Molecular Medicine, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
Jennifer J. Wang
Center for Molecular Medicine, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
Liu Cao
Key Laboratory of Medical Cell Biology, China Medical University, Shenyang 110001, China
Nisha Narayan
Center for Molecular Medicine, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
Marie M. Fergusson
Center for Molecular Medicine, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
Ilsa I. Rovira
Center for Molecular Medicine, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
Michele Allen
Murine Phenotyping Core, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
Danielle A. Springer
Murine Phenotyping Core, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
Cory U. Lago
Center for Molecular Medicine, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
Shuling Zhang
Laboratory of Cancer Biology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Wendy DuBois
Laboratory of Cancer Biology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Theresa Ward
Translational Gerontology Branch, National Institute of Aging, National Institutes of Health, Baltimore, MD 21224, USA
Rafael deCabo
Translational Gerontology Branch, National Institute of Aging, National Institutes of Health, Baltimore, MD 21224, USA
Oksana Gavrilova
Mouse Metabolism Core, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Beverly Mock
Laboratory of Cancer Biology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Toren Finkel
Center for Molecular Medicine, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
DOI
https://doi.org/10.1016/j.celrep.2013.07.030
Journal volume & issue
Vol. 4,
no. 5
Abstract
Read online
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 a number 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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