Abstract
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.
Highlights
The discovery that sirtuins influence yeast replicative lifespan more than 10 years ago sparked wide interest about their biological role in aging, age-related diseases, and calorie restriction (CR)-mediated lifespan extension
The contribution of SIRT1 in both longevity and CR-mediated lifespan extension in lower organisms is a subject of debate (Kaeberlein et al, 2004; Fabrizio et al, 2005), there is evidence that SIRT1 plays an important role in delaying or ameliorating the onset of some age-associated diseases (Herranz et al, 2010)
SIRT1À/À mice on CR displayed a short lifespan (Fig. 1A) (Boily et al, 2008; Li et al, 2008), whereas CR extended the lifespan of both SIRT1+/À and SIRT1+/+ mice by 51% (Fig. 1A and Table S1–S2)
Summary
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 wildtype mice on an ad libitum diet. 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. 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.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
