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

J. Julie Wu, Jie Liu, EdmundB Chen, JenniferJ Wang, Liu Cao, Nisha Narayan, MarieM Fergusson, IlsaI Rovira, Michele Allen, DanielleA Springer, CoryU Lago, Shuling Zhang, Wendy DuBois, Theresa Ward, Rafael deCabo, Oksana Gavrilova, Beverly Mock, Toren Finkel

Research output: Contribution to journalArticle

Abstract

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

Original languageEnglish (US)
Pages (from-to)913-920
Number of pages8
JournalCell Reports
Volume4
Issue number5
DOIs
StatePublished - May 12 2013
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Wu, J. J., Liu, J., Chen, E., Wang, J., Cao, L., Narayan, N., Fergusson, M., Rovira, I., Allen, M., Springer, D., Lago, C., Zhang, S., DuBois, W., Ward, T., deCabo, R., Gavrilova, O., Mock, B., & Finkel, T. (2013). Increased mammalian lifespan and a segmental and tissue-specific slowing of aging after genetic reduction of mTOR expression. Cell Reports, 4(5), 913-920. https://doi.org/10.1016/j.celrep.2013.07.030