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

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 TS...

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Autores principales:	Hong-Mei Zhang, Vivian Diaz, Michael E. Walsh, Yiqiang Zhang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/96ca9655468d43eba1428c6922390f67
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spelling	oai:doaj.org-article:96ca9655468d43eba1428c6922390f672021-12-02T11:52:33ZModerate lifelong overexpression of tuberous sclerosis complex 1 (TSC1) improves health and survival in mice10.1038/s41598-017-00970-72045-2322https://doaj.org/article/96ca9655468d43eba1428c6922390f672017-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00970-7https://doaj.org/toc/2045-2322Abstract 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.Hong-Mei ZhangVivian DiazMichael E. WalshYiqiang ZhangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hong-Mei Zhang Vivian Diaz Michael E. Walsh Yiqiang Zhang Moderate lifelong overexpression of tuberous sclerosis complex 1 (TSC1) improves health and survival in mice
description	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.
format	article
author	Hong-Mei Zhang Vivian Diaz Michael E. Walsh Yiqiang Zhang
author_facet	Hong-Mei Zhang Vivian Diaz Michael E. Walsh Yiqiang Zhang
author_sort	Hong-Mei Zhang
title	Moderate lifelong overexpression of tuberous sclerosis complex 1 (TSC1) improves health and survival in mice
title_short	Moderate lifelong overexpression of tuberous sclerosis complex 1 (TSC1) improves health and survival in mice
title_full	Moderate lifelong overexpression of tuberous sclerosis complex 1 (TSC1) improves health and survival in mice
title_fullStr	Moderate lifelong overexpression of tuberous sclerosis complex 1 (TSC1) improves health and survival in mice
title_full_unstemmed	Moderate lifelong overexpression of tuberous sclerosis complex 1 (TSC1) improves health and survival in mice
title_sort	moderate lifelong overexpression of tuberous sclerosis complex 1 (tsc1) improves health and survival in mice
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/96ca9655468d43eba1428c6922390f67
work_keys_str_mv	AT hongmeizhang moderatelifelongoverexpressionoftuberoussclerosiscomplex1tsc1improveshealthandsurvivalinmice AT viviandiaz moderatelifelongoverexpressionoftuberoussclerosiscomplex1tsc1improveshealthandsurvivalinmice AT michaelewalsh moderatelifelongoverexpressionoftuberoussclerosiscomplex1tsc1improveshealthandsurvivalinmice AT yiqiangzhang moderatelifelongoverexpressionoftuberoussclerosiscomplex1tsc1improveshealthandsurvivalinmice
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Moderate lifelong overexpression of tuberous sclerosis complex 1 (TSC1) improves health and survival in mice

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