title: 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 (Tsc1tg) 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 Tsc1tgmice. Tsc1tgmice are more tolerant to exhaustive exercises and less susceptible to isoproterenol-induced cardiac hypertrophy at both young and advanced ages. Tsc1tgmice have less fibrosis and inflammation in aged as well as isoproterenol-challenged heart than age-matched wild type mice. The female Tsc1tgmice 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 Tsc1tgmice, but not in male Tsc1tgmice. 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.
authors.affiliation: 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.
authors.forename: Hong-Mei
authors.initials: HM
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Vivian
authors.initials: V
authors.lastname: Diaz
authors.affiliation: Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, Texas, 78229, USA.|ETH Zurich, Department of Health Sciences and Technology LFW C 13.2, Universitätstrasse 2, 8092, Zurich, Switzerland.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Walsh
authors.affiliation: 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.
authors.forename: Yiqiang
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D050154:Adiposity / Q000235:genetics; D000818:Animals; D001921:Brain / Q000378:metabolism; D006332:Cardiomegaly / Q000209:etiology / Q000235:genetics; D005260:Female; D007545:Isoproterenol / Q000633:toxicity; D008136:Longevity / Q000235:genetics*; D008297:Male; D000076222:Mechanistic Target of Rapamycin Complex 1 / Q000378:metabolism; D000076225:Mechanistic Target of Rapamycin Complex 2 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D005082:Physical Exertion; D012737:Sex Factors; D015398:Signal Transduction; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C000624651:Tsc1 protein, mouse; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins; D000076222:Mechanistic Target of Rapamycin Complex 1; D000076225:Mechanistic Target of Rapamycin Complex 2; D007545:Isoproterenol