SIRT1 but not its increased expression is essential for lifespan extension in caloric-restricted mice

Aging Cell. 2014 Feb;13(1):193-6. doi: 10.1111/acel.12151. Epub 2013 Nov 19.


The SIRT1 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 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 certain pathologies. Although larger studies in additional genetic backgrounds are needed, these results provide strong initial evidence for the requirement of SIRT1 for the lifespan extension effects of CR, but suggest that its high expression is not required for CR-induced lifespan extension.

Keywords: SIRT1; anti-aging; caloric restriction; lifespan.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Caloric Restriction*
  • Gene Expression Regulation*
  • Longevity* / genetics
  • Mice
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Sirtuin 1 / biosynthesis
  • Sirtuin 1 / genetics*
  • Sirtuin 1 / metabolism*


  • RNA, Messenger
  • Sirtuin 1

Associated data

  • GEO/GSE46895