Journal
AGING CELL
Volume 13, Issue 5, Pages 787-796Publisher
WILEY
DOI: 10.1111/acel.12220
Keywords
healthspan; inflammation; lifespan; muscle wasting; osteoporosis; sirtuins
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Funding
- National Medical Health and Research Council of Australia [RGMS ID 2010-01671]
- NIH [RO1 AR56679]
- Intramural Research Program of the NIA/NIH
- Glenn Foundation for Medical Research
- JDRF UMDF, R01 [AG028730]
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Increased 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.
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