{"doi":"10.1111/acel.14027","title":"<scp>SIRT2</scp> transgenic over‐expression does not impact lifespan in mice","abstract":"<jats:title>Abstract</jats:title><jats:p>The NAD<jats:sup>+</jats:sup>‐dependent deacylase family of sirtuin enzymes have been implicated in biological ageing, late‐life health and overall lifespan, though of these members, a role for sirtuin‐2 (SIRT2) is less clear. Transgenic overexpression of SIRT2 in the BubR1 hypomorph model of progeria can rescue many aspects of health and increase overall lifespan, due to a specific interaction between SIRT2 and BubR1 that improves the stability of this protein. It is less clear whether SIRT2 is relevant to biological ageing outside of a model where BubR1 is under‐expressed. Here, we sought to test whether SIRT2 over‐expression would impact the overall health and lifespan of mice on a nonprogeroid, wild‐type background. While we previously found that SIRT2 transgenic overexpression prolonged female fertility, here, we did not observe any additional impact on health or lifespan, which was measured in both male and female mice on standard chow diets, and in males challenged with a high‐fat diet. At the biochemical level, NMR studies revealed an increase in total levels of a number of metabolites in the brain of SIRT2‐Tg animals, pointing to a potential impact in cell composition; however, this did not translate into functional differences. Overall, we conclude that strategies to enhance SIRT2 protein levels may not lead to increased longevity.</jats:p>","journal":"Aging Cell","year":2023,"id":15084,"datarank":0.3051525839220931,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"self_citation_contribution":0.24141568686511508,"citation_network_contribution":0.06373689705697805,"self_endowment_contribution":0.24141568686511508,"citer_contribution":0.06373689705697805,"corpus_percentile":null,"corpus_rank":null,"citation_count":4,"citer_count":3,"citers_with_citation_signal":3,"citers_with_endowment":3,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":116484,"name":"Corrine E. Fiveash","orcid":null,"position":1,"is_corresponding":false},{"id":116485,"name":"Nicholas L. Bentley","orcid":null,"position":2,"is_corresponding":false},{"id":116486,"name":"Myung‐Jin Kang","orcid":null,"position":3,"is_corresponding":false},{"id":116487,"name":"Hemna Govindaraju","orcid":null,"position":4,"is_corresponding":false},{"id":116488,"name":"Jayne A. Barbour","orcid":"0000-0003-3587-7788","position":5,"is_corresponding":false},{"id":116489,"name":"Brendan P. Wilkins","orcid":null,"position":6,"is_corresponding":false},{"id":116490,"name":"Sarah E. Hancock","orcid":"0000-0001-7541-8901","position":7,"is_corresponding":false},{"id":116491,"name":"Romanthi Madawala","orcid":null,"position":8,"is_corresponding":false},{"id":116492,"name":"Abhijit Das","orcid":"0000-0003-3220-4975","position":9,"is_corresponding":false},{"id":116493,"name":"Hassina Massudi","orcid":null,"position":10,"is_corresponding":false},{"id":116494,"name":"Catherine Li","orcid":null,"position":11,"is_corresponding":false},{"id":116495,"name":"Lynn‐Jee Kim","orcid":null,"position":12,"is_corresponding":false},{"id":116496,"name":"Ashley S. A. Wong","orcid":null,"position":13,"is_corresponding":false},{"id":116497,"name":"Maria B. Marinova","orcid":null,"position":14,"is_corresponding":false},{"id":116498,"name":"Ghazal Sultani","orcid":null,"position":15,"is_corresponding":false},{"id":116499,"name":"Abhirup Das","orcid":null,"position":16,"is_corresponding":false},{"id":116500,"name":"Neil A. Youngson","orcid":"0000-0003-0690-4580","position":17,"is_corresponding":false},{"id":116501,"name":"David G. Le Couteur","orcid":"0000-0002-4227-5817","position":18,"is_corresponding":false},{"id":106661,"name":"David Sinclair","orcid":"0000-0002-9936-436X","position":19,"is_corresponding":false},{"id":116502,"name":"Nigel Turner","orcid":"0000-0002-0119-9328","position":20,"is_corresponding":false},{"id":116483,"name":"Lindsay E. Wu","orcid":"0000-0002-1599-7574","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":1.6094379124341003,"endowment":1.6094379124341003,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"38009412","pmcid":"PMC10726910","openalex_id":"https://openalex.org/W4389038136","authors":[],"funders":[{"funder_name":"American Federation for Aging Research","grant_id":"AFAR/Hevolution New Investigator Award","title":null},{"funder_name":"National Health and Medical Research Council","grant_id":"APP1066172","title":null},{"funder_name":"National Health and Medical Research Council","grant_id":"APP1127821","title":null},{"funder_name":"National Health and Medical Research Council (NHMRC)","grant_id":"1127821","title":"Preserving ovarian function during chemotherapy and old age"},{"funder_name":"National Health and Medical Research Council (NHMRC)","grant_id":"1066172","title":"NAD+ and SIRT2 regulation of mitotic lifespan, senescence and healthy ageing"}],"total_grants":5,"fwci":0.6643,"citation_percentile":0.68824055,"influential_citations":0,"citation_trend":[{"year":2023,"count":1},{"year":2024,"count":1},{"year":2025,"count":2}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/acel.14027","host_type":"journal"},{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/acel.14027","host_type":"GOLD"},{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/acel.14027","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1111/acel.14027","host_type":"publisher"},{"url":"https://doi.org/10.1111/acel.14027","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/38009412","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/10726910","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC10726910/pdf/ACEL-22-e14027.pdf","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC10726910","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC10726910?pdf=render","host_type":"Europe_PMC"},{"url":"http://dx.doi.org/10.1111/acel.14027","host_type":""}],"fields_of_study":["Sirtuins and Resveratrol in Medicine","Adipose Tissue and Metabolism","Mitochondrial Function and Pathology","Medicine","Biology","Animals","Female","Male","Mice","Aging","Animals, Genetically Modified","Brain","Longevity","Sirtuin 2"],"mesh_terms":["Aging","Animals","Brain","Female","Longevity","Male","Animals, Genetically Modified","Mice","Sirtuin 2"],"keywords":["SIRT2","Sirtuin","Longevity","Biology","Genetically modified mouse","Transgene","Sirtuin 1","Ageing","NAD+ kinase","Internal medicine","Endocrinology","Cell biology","Genetics","Enzyme","Gene","Medicine","Biochemistry","Downregulation and upregulation","Aging","Lifespan","Healthspan","Sirtuins","Aging Biology","Sirtuin 2 (Sirt2)","Male","Animals, Genetically Modified","Mice","Sirtuin 2","Animals","Brain","Female","Research Articles"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-01T16:19:50.308558Z","pmid":null,"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":[]}