{"doi":"10.1093/genetics/iyaf185","title":"Mitochondrial sirtuins <i>sir-2.2</i> and <i>sir-2.3</i> regulate lifespan in <i>C. elegans</i>","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.","journal":"Genetics","year":2025,"id":546681,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9592,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":647318,"name":"Latisha Franklin","orcid":null,"position":1,"is_corresponding":false},{"id":1438776,"name":"Sampurna Sattar","orcid":"0000-0001-5244-1367","position":2,"is_corresponding":false},{"id":1119701,"name":"Corinna A. Moro","orcid":"0009-0008-8112-6620","position":3,"is_corresponding":false},{"id":1124895,"name":"Michael V. DeGennaro","orcid":null,"position":4,"is_corresponding":false},{"id":1439187,"name":"Nicole G LaGanke","orcid":null,"position":5,"is_corresponding":false},{"id":646636,"name":"Wendy Hanna‐Rose","orcid":"0000-0002-5566-4758","position":6,"is_corresponding":false},{"id":1438775,"name":"Sarah M Chang","orcid":"0000-0002-0036-1071","position":0,"is_corresponding":true}],"reference_count":46,"raw_metadata":null,"created_at":"2026-07-19T02:53:36.567932Z","pmid":"40908783","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}