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Updated: May 8, 2026
A Suppressor Screen for the Characterization of Genetic Links Regulating Chronological Lifespan in Saccharomyces cerevisiae
Published on: September 17, 2020
SIRT1 but not its increased expression is essential for lifespan extension in caloric-restricted mice
Evi M Mercken1, Jia Hu, Susan Krzysik-Walker
1Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD, 21224, USA.
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.
Insights
Calorie restriction (CR) extends lifespan, but the role of SIRT1 deacetylase is unclear. This study shows SIRT1 is required for CR
Area of Science:
- Aging Research
- Genetics
- Molecular Biology
Background:
- Sirtuin 1 (SIRT1) deacetylase is a key molecule studied for calorie restriction's (CR) anti-aging effects.
- Its specific role in CR-mediated lifespan extension remains unproven.
- Previous work showed SIRT1 knockout mice had reduced lifespan on a normal diet.
Purpose of the Study:
- To investigate the necessity of SIRT1 for lifespan extension induced by calorie restriction (CR).
- To determine if SIRT1 is required for the beneficial effects of CR on longevity.
Main Methods:
- Studied calorie restriction (CR) in wild-type and SIRT1 heterozygous (+/-) mice.
- Compared median lifespan and pathology frequency between groups.
- Analyzed the impact of reduced SIRT1 levels on CR's lifespan-extending effects.
Main Results:
- SIRT1 heterozygous mice on CR showed identical median lifespan extension (51%) compared to wild-type mice on CR.
- However, SIRT1 heterozygous mice exhibited an increased incidence of specific pathologies.
- These findings suggest SIRT1 is essential for CR's lifespan benefits, but high expression isn't necessary.
Conclusions:
- SIRT1 is required for calorie restriction (CR) to extend lifespan.
- High SIRT1 expression is not essential for CR-induced longevity.
- Further research in diverse genetic backgrounds is recommended.
