Mercken, Evi MMitchell, Sarah JMartin-Montalvo, AlejandroMinor, Robin KAlmeida, MariaGomes, Ana PScheibye-Knudsen, MortenPalacios, Hector HLicata, Jordan JZhang, YongqingBecker, Kevin GKhraiwesh, HusamGonzález-Reyes, José AVillalba, José MBaur, Joseph AElliott, PeterWestphal, ChristophVlasuk, George PEllis, James LSinclair, DavidBernier, Michelde Cabo, Rafael2015-03-022014Mercken, E. M., S. J. Mitchell, A. Martin-Montalvo, R. K. Minor, M. Almeida, A. P. Gomes, M. Scheibye-Knudsen, et al. 2014. “SRT2104 extends survival of male mice on a standard diet and preserves bone and muscle mass.” Aging Cell 13 (5): 787-796. doi:10.1111/acel.12220. http://dx.doi.org/10.1111/acel.12220.1474-9718http://nrs.harvard.edu/urn-3:HUL.InstRepos:14065485Increased expression of SIRT1 extends the lifespan of lower organisms and delays the onset of age-related diseases in mammals. Here, we show that SRT2104, a synthetic small molecule activator of SIRT1, extends both mean and maximal lifespan of mice fed a standard diet. This is accompanied by improvements in health, including enhanced motor coordination, performance, bone mineral density, and insulin sensitivity associated with higher mitochondrial content and decreased inflammation. Short-term SRT2104 treatment preserves bone and muscle mass in an experimental model of atrophy. These results demonstrate it is possible to design a small molecule that can slow aging and delay multiple age-related diseases in mammals, supporting the therapeutic potential of SIRT1 activators in humans.en-UShealthspaninflammationlifespanmuscle wastingosteoporosissirtuinsJournal Article2015-03-0210.1111/acel.12220