Open AccessSIRT 1 but not its increased expression is essential for lifespan extension in caloric‐restricted mice
Author(s) -
Mercken Evi M.,
Hu Jia,
KrzysikWalker Susan,
Wei Min,
Li Ying,
McBurney Michael W.,
Cabo Rafael,
Longo Valter D.
Publication year - 2014
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.12151
Subject(s) - biology , calorie restriction , caloric theory , life extension , longevity , wild type , heterozygote advantage , extension (predicate logic) , endocrinology , medicine , genetics , allele , gene , mutant , computer science , programming language
Summary The SIRT 1 deacetylase is one of the best‐studied putative 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 SIRT 1 displayed a shorter median lifespan than wild‐type mice on an ad libitum diet. Here, we report that median lifespan extension in CR heterozygote SIRT 1 +/− mice was identical (51%) to that observed in wild‐type mice, but SIRT 1 +/− mice displayed a higher frequency of certain pathologies. Although larger studies in additional genetic backgrounds are needed, these results provide strong initial evidence for the requirement of SIRT 1 for the lifespan extension effects of CR , but suggest that its high expression is not required for CR ‐induced lifespan extension.