@article{873cc215cbb148869c1f8b1587632140,
title = "SRT1720 improves survival and healthspan of obese mice",
abstract = "Sirt1 is an NAD+-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-1α-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.",
author = "Minor, {Robin K.} and Baur, {Joseph A.} and Gomes, {Ana P.} and Ward, {Theresa M.} and Anna Csiszar and Mercken, {Evi M.} and Kotb Abdelmohsen and Shin, {Yu Kyong} and Carles Canto and Morten Scheibye-Knudsen and Melissa Krawczyk and Irusta, {Pablo M.} and Alejandro Mart{\'i}n-Montalvo and Hubbard, {Basil P.} and Yongqing Zhang and Elin Lehrmann and White, {Alexa A.} and Price, {Nathan L.} and Swindell, {William R.} and Pearson, {Kevin J.} and Becker, {Kevin G.} and Bohr, {Vilhelm A.} and Myriam Gorospe and Egan, {Josephine M.} and Talan, {Mark I.} and Johan Auwerx and Westphal, {Christoph H.} and Ellis, {James L.} and Zoltan Ungvari and Vlasuk, {George P.} and Elliott, {Peter J.} and Sinclair, {David A.} and {De Cabo}, Rafael",
note = "Funding Information: This research was conducted under a Cooperative Research and Development Agreement (CRADA) between Sirtris, a GSK Company, and the National Institute on Aging, National Institutes of Health (NIA/NIH). Microarray data are archived under the accession number GSE19102. JAB is supported by NIH Pathway to Independence Award R00AG031182. We are grateful to Dawn Nines, Dawn Phillips and Justine Lucas for their excellent animal care. We also thank Larry Brant for help with data analyses and Olga Carlson for technical assistance. Funding was provided by the Intramural Research Program of the NIA/NIH, the Swiss National Science Foundation and the ERC Ideas program. Funding to DAS was provided by the NIH/NIA Extramural Research Program and the Glenn Foundation for Medical Research.",
year = "2011",
doi = "10.1038/srep00070",
language = "English (US)",
volume = "1",
journal = "Scientific reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
}