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 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.

SUBMITTER: Zhang HM 

PROVIDER: S-EPMC5429778 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature