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

Zhang, Hong-Mei, Diaz, Vivian, Walsh, Michael E., Zhang, Yiqiang·2017·Scientific Reports
DOI 10.1038/s41598-017-00970-7PMC PMC5429778
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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.

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Metadata

Authors
Zhang, H.-M., Diaz, V., Walsh, M. E., & Zhang, Y.
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2017-04-11
Volume
7
Issue
1
ISSN
2045-2322
DOI
10.1038/s41598-017-00970-7
PMC
PMC5429778
Cited by
31
References
11
Language
en
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