{"doi":"10.1101/2024.03.12.584678","title":"Protection against <i>APOE4</i> -associated aging phenotypes with the longevity-promoting intervention 17α-estradiol in male mice","abstract":"Summary The apolipoprotein ε4 allele ( APOE4 ) is associated with decreased longevity, increased vulnerability to age-related declines, and disorders across multiple systems. Interventions that promote healthspan and lifespan represent a promising strategy to attenuate the development of APOE4 -associated aging phenotypes. Here we studied the ability of the longevity-promoting intervention 17α-estradiol (17αE2) to protect against age-related impairments in APOE4 versus the predominant APOE3 genotype using early middle-aged mice with knock-in of human APOE alleles. Beginning at age 10 months, male APOE3 or APOE4 mice were treated for 20 weeks with 17αE2 or vehicle then compared for indices of aging phenotypes body-wide. Across peripheral and neural measures, APOE4 was associated with poorer outcomes. Notably, 17αE2 treatment improved outcomes in a genotype-dependent manner favoring APOE4 mice. These data demonstrate a positive APOE4 bias in 17αE2-mediated healthspan actions, suggesting that longevity-promoting interventions may be useful in mitigating deleterious age-related risks associated with APOE4 genotype.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":490311,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"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":0.9632,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":493892,"name":"Amy Christensen","orcid":"0000-0002-3357-0523","position":1,"is_corresponding":false},{"id":1284261,"name":"Wenjie Qian","orcid":"0000-0002-7219-5850","position":2,"is_corresponding":false},{"id":876542,"name":"Max A. Thorwald","orcid":"0000-0003-0095-5344","position":3,"is_corresponding":false},{"id":1335686,"name":"Jose Godoy Lugo","orcid":null,"position":4,"is_corresponding":false},{"id":1335687,"name":"Sara Namvari","orcid":null,"position":5,"is_corresponding":false},{"id":1335688,"name":"Olivia S. White","orcid":null,"position":6,"is_corresponding":false},{"id":458324,"name":"Caleb E. Finch","orcid":"0000-0002-7617-3958","position":7,"is_corresponding":false},{"id":260354,"name":"Bérénice A. Benayoun","orcid":"0000-0002-7401-4777","position":8,"is_corresponding":false},{"id":423784,"name":"Christian J. Pike","orcid":"0000-0003-4577-7668","position":9,"is_corresponding":false},{"id":564989,"name":"Cassandra McGill","orcid":"0000-0002-0524-5061","position":0,"is_corresponding":true}],"reference_count":93,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:08:32.775003Z","pmid":"38559059","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":[]}