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Published on: September 17, 2020
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Sirtuins are Not Conserved Longevity Genes
1Department of Diabetes & Cancer Metabolism, Beckman Research Institute of City of Hope, Duarte, CA 91010 USA.
Life Metabolism
|April 10, 2023
Summary
Sirtuins, initially studied for yeast longevity, are not conserved in animal lifespan. Despite extensive research, evidence does not support sirtuins as key longevity genes or mediators of NAD repletion benefits.
Area of Science:
- Biology
- Genetics
- Aging Research
Background:
- Sequence conservation often implies functional conservation in biology.
- Animal longevity is a complex trait influenced by various factors.
- The yeast SIR2 gene was initially linked to extended replicative lifespan.
Purpose of the Study:
- To critically evaluate the role of sirtuins in animal longevity.
- To investigate the conserved function of SIR2 homologs across species.
- To reassess the connection between sirtuins, aging, and NAD repletion.
Main Methods:
- Review of existing literature on sirtuin function and longevity studies.
- Analysis of conserved targets and functions of SIR2 homologs.
- Examination of evidence for sirtuins in yeast and animal aging models.
Main Results:
- SIR2's role in yeast longevity is not a selected trait and its targets are not conserved.
- Sirtuin homologs overexpressed in invertebrates yielded artifactual positive results.
- SIR2 acts as a pro-aging gene in yeast chronological aging and in flies under amino acid deprivation.
Conclusions:
- The notion that sirtuins are specifically connected to animal lifespan lacks robust evidence.
- Sirtuins are unlikely to be primary mediators of NAD repletion's beneficial effects on longevity.
- Previous research on sirtuins and longevity may have been influenced by biases.
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