{"doi":"10.1111/acel.13100","title":"The lipid elongation enzyme ELOVL2 is a molecular regulator of aging in the retina","abstract":"Methylation of the regulatory region of the elongation of very-long-chain fatty acids-like 2 (ELOVL2) gene, an enzyme involved in elongation of long-chain polyunsaturated fatty acids, is one of the most robust biomarkers of human age, but the critical question of whether ELOVL2 plays a functional role in molecular aging has not been resolved. Here, we report that Elovl2 regulates age-associated functional and anatomical aging in vivo, focusing on mouse retina, with direct relevance to age-related eye diseases. We show that an age-related decrease in Elovl2 expression is associated with increased DNA methylation of its promoter. Reversal of Elovl2 promoter hypermethylation in vivo through intravitreal injection of 5-Aza-2'-deoxycytidine (5-Aza-dc) leads to increased Elovl2 expression and rescue of age-related decline in visual function. Mice carrying a point mutation C234W that disrupts Elovl2-specific enzymatic activity show electrophysiological characteristics of premature visual decline, as well as early appearance of autofluorescent deposits, well-established markers of aging in the mouse retina. Finally, we find deposits underneath the retinal pigment epithelium in Elovl2 mutant mice, containing components found in human drusen, a pathologic hallmark of age related macular degeneration. These findings indicate that ELOVL2 activity regulates aging in mouse retina, provide a molecular link between polyunsaturated fatty acids elongation and visual function, and suggest novel therapeutic strategies for the treatment of age-related eye diseases.","journal":"Aging Cell","year":2020,"id":53894,"datarank":0.7077748306942643,"base_score":4.718498871295094,"endowment":4.718498871295094,"self_citation_contribution":0.7077748306942643,"citation_network_contribution":0.0,"self_endowment_contribution":0.7077748306942643,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":111,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9535,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":275688,"name":"Daniel L. Chao","orcid":"0000-0001-9174-8118","position":1,"is_corresponding":false},{"id":276690,"name":"Lorena Rocha","orcid":null,"position":2,"is_corresponding":false},{"id":233750,"name":"Matthew J. Kolar","orcid":"0000-0001-8054-9121","position":3,"is_corresponding":false},{"id":275689,"name":"Viet Anh Nguyen Huu","orcid":"0000-0002-8909-0203","position":4,"is_corresponding":false},{"id":275690,"name":"Michał Krawczyk","orcid":"0000-0001-9646-3779","position":5,"is_corresponding":false},{"id":276691,"name":"Manish Dasyani","orcid":null,"position":6,"is_corresponding":false},{"id":275691,"name":"Tina Wang","orcid":"0000-0002-8035-3134","position":7,"is_corresponding":false},{"id":275692,"name":"Maryam Jafari","orcid":"0000-0001-5552-1127","position":8,"is_corresponding":false},{"id":276692,"name":"Mary Jabari","orcid":null,"position":9,"is_corresponding":false},{"id":275693,"name":"Kevin D. Ross","orcid":"0000-0003-1224-3950","position":10,"is_corresponding":false},{"id":17868,"name":"Alan Saghatelian","orcid":"0000-0002-0427-563X","position":11,"is_corresponding":false},{"id":275694,"name":"Bruce A. Hamilton","orcid":"0000-0001-5599-9139","position":12,"is_corresponding":false},{"id":2996,"name":"Kang Zhang","orcid":"0000-0002-4549-1697","position":13,"is_corresponding":false},{"id":275695,"name":"Dorota Skowronska‐Krawczyk","orcid":"0000-0002-5758-4225","position":14,"is_corresponding":false},{"id":275687,"name":"Daniel Chen","orcid":"0000-0002-4716-549X","position":0,"is_corresponding":true}],"reference_count":59,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T20:45:25.145885Z","pmid":"31943697","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":[]}