{"doi":"10.3390/cells13201727","title":"Hymecromone Promotes Longevity and Insulin Sensitivity in Mice","abstract":"Given that the extracellular matrix polymer hyaluronan (HA) has been implicated in longevity, we asked whether 4-methylumbelliferone (4-MU), an inhibitor of HA synthesis, impacts lifespan in mice. We designed a prospective study of long-term administration of 4-MU with conventional C57BL/6J mice. We find that 4-MU extends median survival from 122 weeks (control) to 154 weeks (4-MU), an increase of 32 weeks (p < 0.0001 by Log-rank Mantel Cox test). The maximum lifespan of 4-MU treated mice increased from 159 to 194 weeks. In tandem with these effects, 4-MU enhances insulin sensitivity, a metabolic parameter known to regulate lifespan, as measured by insulin tolerance testing (ITT) as well as frequent sampling intra venous glucose tolerance tests (FSIVGTTs). We further observed that 4-MU treated mice weigh less while consuming the same amount of food, indicating that 4-MU treatment alters energy expenditure. However, we do not observe changes in tissue HA content in this model. We conclude that 4-MU promotes insulin sensitivity and longevity but that the underlying mechanism, and the contribution of HA is unclear. 4-MU, already approved in various countries for hepatobiliary conditions, is currently under investigation and clinical development as a therapy for several chronic inflammatory conditions. These data suggest that the beneficial effects of 4-MU on tissue metabolism may include effects on longevity.","journal":"Cells","year":2024,"id":449417,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9578,"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":304459,"name":"Kathryn S. Czepiel","orcid":"0000-0002-6928-0122","position":1,"is_corresponding":false},{"id":381353,"name":"Gernot Kaber","orcid":"0000-0002-6184-5192","position":2,"is_corresponding":false},{"id":341656,"name":"Darko Stefanovski","orcid":"0000-0002-4654-0569","position":3,"is_corresponding":false},{"id":382285,"name":"Aviv Hargil","orcid":null,"position":4,"is_corresponding":false},{"id":989435,"name":"Nina Pennetzdorfer","orcid":"0000-0002-5468-8715","position":5,"is_corresponding":false},{"id":1269172,"name":"Robert W. Targ","orcid":null,"position":6,"is_corresponding":false},{"id":911168,"name":"Saranya Chidambaranathan Reghupaty","orcid":"0000-0001-6660-1296","position":7,"is_corresponding":false},{"id":237278,"name":"Thomas N. Wight","orcid":"0000-0002-2794-4197","position":8,"is_corresponding":false},{"id":382286,"name":"Robert B. Vernon","orcid":null,"position":9,"is_corresponding":false},{"id":7358,"name":"Rebecca L. Hull-Meichle","orcid":null,"position":10,"is_corresponding":false},{"id":381351,"name":"Payton L. Marshall","orcid":"0000-0002-0921-3016","position":11,"is_corresponding":false},{"id":1171356,"name":"Carlos Medina","orcid":"0000-0002-8324-7994","position":12,"is_corresponding":false},{"id":381358,"name":"Hunter A. Martinez","orcid":"0000-0003-1129-3382","position":13,"is_corresponding":false},{"id":1268743,"name":"Anissa Kalinowski","orcid":"0000-0003-3298-5580","position":14,"is_corresponding":false},{"id":939615,"name":"Rudolph D. Paladini","orcid":null,"position":15,"is_corresponding":false},{"id":266862,"name":"Stavros Garantziotis","orcid":"0000-0003-4007-375X","position":16,"is_corresponding":false},{"id":7140,"name":"Joshua W. Knowles","orcid":"0000-0003-1922-7240","position":17,"is_corresponding":false},{"id":239766,"name":"Paul L. Bollyky","orcid":"0000-0003-2499-9448","position":18,"is_corresponding":false},{"id":381352,"name":"Nadine Nagy","orcid":"0000-0002-2638-2436","position":0,"is_corresponding":true}],"reference_count":79,"raw_metadata":null,"created_at":"2026-07-19T02:02:16.291892Z","pmid":"39451245","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":[]}