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Sci Rep. 2017 Apr 11;7(1):834. doi: 10.1038/s41598-017-00970-7.

Moderate lifelong overexpression of tuberous sclerosis complex 1 (TSC1) improves health and survival in mice.

Author information

1
Department of Oncology, Xijing Hospital, Fourth Military Medical University, No. 169, Changle West Road, Xi'an, Shanxi, 710032, P. R. China. zhm@fmmu.edu.cn.
2
Sam and Ann Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, Texas, 78229, USA.
3
Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, Texas, 78229, USA.
4
ETH Zurich, Department of Health Sciences and Technology LFW C 13.2, Universitätstrasse 2, 8092, Zurich, Switzerland.
5
Greehey Children's Cancer Research Institute, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, Texas, 78229, USA. zhangy@uthscsa.edu.

Abstract

The tuberous sclerosis complex 1/2 (TSC1/2) is an endogenous regulator of the mechanistic target of rapamycin (mTOR). While mTOR has been shown to play an important role in health and aging, the role of TSC1/2 in aging has not been fully investigated. In the current study, a constitutive TSC1 transgenic (Tsc1 tg ) mouse model was generated and characterized. mTORC1 signaling was reduced in majority of the tissues, except the brain. In contrast, mTORC2 signaling was enhanced in Tsc1 tg mice. Tsc1 tg mice are more tolerant to exhaustive exercises and less susceptible to isoproterenol-induced cardiac hypertrophy at both young and advanced ages. Tsc1 tg mice have less fibrosis and inflammation in aged as well as isoproterenol-challenged heart than age-matched wild type mice. The female Tsc1 tg mice exhibit a higher fat to lean mass ratio at advanced ages than age-matched wild type mice. More importantly, the lifespan increased significantly in female Tsc1 tg mice, but not in male Tsc1 tg mice. Collectively, our data demonstrated that moderate increase of TSC1 expression can enhance overall health, particularly cardiovascular health, and improve survival in a gender-specific manner.

PMID:
28400571
PMCID:
PMC5429778
DOI:
10.1038/s41598-017-00970-7
[Indexed for MEDLINE]
Free PMC Article

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