論文 - 詳細
| RRC ID | 88162 |
|---|---|
| 著者 | Chang SM, Franklin LP, Sattar S, Moro CA, DeGennaro MV, LaGanke NG, Hanna-Rose W. |
| タイトル | Mitochondrial sirtuins sir-2.2 and sir-2.3 regulate lifespan in C. elegans. |
| ジャーナル | Genetics |
| Abstract |
Mitochondrial sirtuins regulate metabolism and are emerging drug targets for metabolic and age-related diseases such as cancer, diabetes, and neurodegeneration. Yet, the extent of their functions remains unclear. Here, we uncover a physiological role for the Caenorhabditis elegans mitochondrial sirtuins, sir-2.2 and sir-2.3, in lifespan regulation. Using genetic alleles with deletions that destroy catalytic activity, we demonstrate that sir-2.2 and sir-2.3 mutants live an average of 25% longer than controls when fed the normal lab diet of live E. coli OP50. While decreased consumption of food is a known mechanism for lifespan extension, we did not find evidence of reduced pharyngeal pumping. Interestingly, lifespan extension effected by loss of sir-2.2 or sir-2.3 is sensitive to the diet. The lifespan extension of the sir-2.2 mutants is eliminated and that of sir-2.3 mutants is attenuated when the animals are fed the E. coli strain HT115, which is typically used for RNAi experiments. We used growth ability of the food source and a virulent pathogenic strain to ask if differences in pathogenicity are related to the mechanisms for lifespan extension. sir-2.3 deletion results in lifespan extension in all conditions. However, removing the ability of the food source to grow eliminated the sir-2-mediated effect. We also examine the response of the mutants to oxidative stress, and our results suggest that a hormetic response contributes to lifespan extension in both mutants. Our data suggest that sir-2.2 and sir-2.3 use overlapping yet distinct mechanisms for regulating lifespan. |
| 巻・号 | 231(3) |
| 公開日 | 2025-11-12 |
| DOI | 10.1093/genetics/iyaf185 |
| PII | 8248209 |
| PMID | 40908783 |
| PMC | PMC12428508 |
| MeSH | Animals Caenorhabditis elegans* / genetics Caenorhabditis elegans* / physiology Caenorhabditis elegans Proteins* / genetics Caenorhabditis elegans Proteins* / metabolism Escherichia coli / pathogenicity Longevity* / genetics Mitochondria* / genetics Mitochondria* / metabolism Mutation Sirtuin 2* / genetics Sirtuin 2* / metabolism Sirtuins* / genetics Sirtuins* / metabolism |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Bluesky |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 線虫 | tm2673 |