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

doi:10.1016/j.celrep.2013.07.030

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
pp. 913 – 920

Abstract

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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.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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