{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T23:56:16Z","timestamp":1790898976899,"version":"4.1.0"},"reference-count":66,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,4,11]],"date-time":"2017-04-11T00:00:00Z","timestamp":1491868800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,4,11]],"date-time":"2017-04-11T00:00:00Z","timestamp":1491868800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>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 (<jats:italic>Tsc1<\/jats:italic><jats:sup>\n                  <jats:italic>tg<\/jats:italic>\n                <\/jats:sup>) 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 <jats:italic>Tsc1<\/jats:italic><jats:sup>\n                  <jats:italic>tg<\/jats:italic>\n                <\/jats:sup> mice. <jats:italic>Tsc1<\/jats:italic><jats:sup>\n                  <jats:italic>tg<\/jats:italic>\n                <\/jats:sup> mice are more tolerant to exhaustive exercises and less susceptible to isoproterenol-induced cardiac hypertrophy at both young and advanced ages. <jats:italic>Tsc1<\/jats:italic><jats:sup>\n                  <jats:italic>tg<\/jats:italic>\n                <\/jats:sup> mice have less fibrosis and inflammation in aged as well as isoproterenol-challenged heart than age-matched wild type mice. The female <jats:italic>Tsc1<\/jats:italic><jats:sup>\n                  <jats:italic>tg<\/jats:italic>\n                <\/jats:sup> 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 <jats:italic>Tsc1<\/jats:italic><jats:sup>\n                  <jats:italic>tg<\/jats:italic>\n                <\/jats:sup> mice, but not in male <jats:italic>Tsc1<\/jats:italic><jats:sup>\n                  <jats:italic>tg<\/jats:italic>\n                <\/jats:sup> 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.<\/jats:p>","DOI":"10.1038\/s41598-017-00970-7","type":"journal-article","created":{"date-parts":[[2017,4,5]],"date-time":"2017-04-05T15:45:40Z","timestamp":1491407140000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Moderate lifelong overexpression of tuberous sclerosis complex 1 (TSC1) improves health and survival in mice"],"prefix":"10.1038","volume":"7","author":[{"given":"Hong-Mei","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivian","family":"Diaz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael E.","family":"Walsh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiqiang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,4,11]]},"reference":[{"key":"970_CR1","doi-asserted-by":"publisher","unstructured":"Dazert, E. & Hall, M. 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