E-GEOD-46895 - SIRT1 but not its increased expression is essential for lifespan extension in caloric restricted mice
Released on 25 April 2014, last updated on 13 May 2014
The SIRT1 deacetylase is one of the best-studied potential mediators of some of the anti-aging effects of calorie restriction (CR); but its role in CR-dependent lifespan extension has not been demonstrated. We previously found that mice lacking both copies of SIRT1 displayed a shorter median lifespan than wild type mice on an ad libitum diet. Here we report that median lifespan extension in CR heterozygote SIRT1+/- mice was identical (51%) to that observed in wild type mice but SIRT1+/- mice displayed a higher frequency of some certain pathologies. Although larger studies in different genetic backgrounds are necessary , these results provide strong initial evidence for the requirement of SIRT1 for the anti-aging effects of CR, but suggest that its high expression is not required for CR-induced lifespan extension. Key words: SIRT1, caloric restriction, lifespan, anti-aging 2-5 month old male mice of 3 different genotypes (SIRT1+/+, SIRT1+/-, and SIRT1-/-) that had normal, reduced or no expression of SIRT1 were treated with either a 40% caloric restricted diet (CR) or an ad libitum diet (AL). 2-4 replicates of each experimental condition were used in the analysis.
transcription profiling by array
Kevin G Becker <email@example.com>, Evi M Mercken, Jia Hu, Michael W McBurney, Min Wei, Rafael de Cabo, Susan Krzysik-Walker, Valter D Longo, Ying Li
SIRT1 but not its increased expression is essential for lifespan extension in caloric-restricted mice. Mercken EM, Hu J, Krzysik-Walker S, Wei M, Li Y, McBurney MW, de Cabo R, Longo VD. , Europe PMC 23941528