SRT1720 improves survival and healthspan of obese mice

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SRT1720 improves survival and healthspan of obese mice

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Title: SRT1720 improves survival and healthspan of obese mice
Author: Minor, Robin K.; Baur, Joseph A.; Gomes, Ana P.; Ward, Theresa M.; Csiszar, Anna; Mercken, Evi M.; Abdelmohsen, Kotb; Shin, Yu-Kyong; Canto, Carles; Scheibye-Knudsen, Morten; Krawczyk, Melissa; Irusta, Pablo M.; Martín-Montalvo, Alejandro; Hubbard, Basil; Zhang, Yongqing; Lehrmann, Elin; White, Alexa A.; Price, Nathan; Swindell, William; Pearson, Kevin J.; Becker, Kevin G.; Bohr, Vilhelm A.; Gorospe, Myriam; Egan, Josephine M.; Talan, Mark I.; Auwerx, Johan; Westphal, Christoph H.; Ellis, James L.; Ungvari, Zoltan; Vlasuk, George P.; Elliott, Peter J.; Sinclair, David Andrew; de Cabo, Rafael

Note: Order does not necessarily reflect citation order of authors.

Citation: Minor, Robin K., Joseph A. Baur, Ana P. Gomes, Theresa M. Ward, Anna Csiszar, Evi M. Mercken, Kotb Abdelmohsen, et al. 2011. “SRT1720 Improves Survival and Healthspan of Obese Mice.” Scientific Reports 1 (August 18). doi:10.1038/srep00070.
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Abstract: Sirt1 is an NAD1-dependent deacetylase that extends lifespan in lower organisms and improves metabolism and delays the onset of age-related diseases in mammals. Here we show that SRT1720, a synthetic compound that was identified for its ability to activate Sirt1 in vitro, extends both mean and maximum lifespan of adult mice fed a high-fat diet. This lifespan extension is accompanied by health benefits including reduced liver steatosis, increased insulin sensitivity, enhanced locomotor activity and normalization of gene expression profiles and markers of inflammation and apoptosis, all in the absence of any observable toxicity. Using a conditional SIRT1 knockout mouse and specific gene knockdowns we show SRT1720 affects mitochondrial respiration in a Sirt1- and PGC-1a-dependent manner. These findings indicate that SRT1720 has long-term benefits and demonstrate for the first time the feasibility of designing novel molecules that are safe and effective in promoting longevity and preventing multiple age-related diseases in mammals.
Published Version: doi:10.1038/srep00070
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3216557/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:27364289
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