{"doi":"10.1371/journal.pgen.1011704","title":"Age-associated decline of Coenzyme A leads to intestinal stem cells dysfunction via disturbing iron homeostasis","abstract":"<jats:p>The decline in adult stem cell performance is closely linked to tissue malfunction and the rising incidence of age-related diseases. To investigate the molecular basis of these impairments, our screening strategy identified reduced activity in the pantothenate/coenzyme A (CoA) pathway within aged ISCs. Furthermore, exogenous CoA supplementation restructured ISC metabolic pathways, reversing age-induced hyperproliferation and intestinal dysfunction, and thus extending <jats:italic>Drosophila</jats:italic> lifespan by curbing excessive iron accumulation in ISCs. These findings uncover a new mechanism of stem cell aging and propose that pantothenate and CoA could be potential therapeutic targets for treating age-related diseases and enhancing healthy aging in humans.</jats:p>","journal":"PLOS Genetics","year":2025,"id":607952,"datarank":0.16479184330021646,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.0,"self_endowment_contribution":0.16479184330021646,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"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":1072710,"name":"Gang Du","orcid":"0000-0003-0805-4778","position":1,"is_corresponding":false},{"id":258849,"name":"Yi Chen","orcid":"0000-0001-5329-4987","position":2,"is_corresponding":false},{"id":79905,"name":"Haiyang Chen","orcid":"0000-0002-2671-1199","position":3,"is_corresponding":false},{"id":1178728,"name":"Zhiming Liu","orcid":"0000-0002-4030-862X","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Age-associated decline of Coenzyme A leads to intestinal stem cells dysfunction via disturbing iron homeostasis","abstract":"<jats:p>The decline in adult stem cell performance is closely linked to tissue malfunction and the rising incidence of age-related diseases. To investigate the molecular basis of these impairments, our screening strategy identified reduced activity in the pantothenate/coenzyme A (CoA) pathway within aged ISCs. Furthermore, exogenous CoA supplementation restructured ISC metabolic pathways, reversing age-induced hyperproliferation and intestinal dysfunction, and thus extending <jats:italic>Drosophila</jats:italic> lifespan by curbing excessive iron accumulation in ISCs. These findings uncover a new mechanism of stem cell aging and propose that pantothenate and CoA could be potential therapeutic targets for treating age-related diseases and enhancing healthy aging in humans.</jats:p>","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"40446021","pmcid":"PMC12151469","openalex_id":null,"authors":[],"funders":[{"funder_name":"the National Key Basic Research Program of China","grant_id":"2020YFA0803602","title":null},{"funder_name":"the National Natural Science Foundation of China","grant_id":"32470879, 92157109","title":null},{"funder_name":"Sichuan University","grant_id":"ZYYC20024","title":null},{"funder_name":"Sichuan Science and Technology Program, Sichuan Provincial Natural Science Foundation","grant_id":"2025ZNSFSC0720","title":null},{"funder_name":"Natural Science Foundation of Sichuan Province","grant_id":"2023NSFSC0664","title":null},{"funder_name":"Noncommunicable Chronic Diseases-National Science and Technology Major Project","grant_id":"2023ZD0506800","title":null}],"total_grants":6,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://doi.org/10.1371/journal.pgen.1011704","host_type":"publisher"},{"url":"https://dx.plos.org/10.1371/journal.pgen.1011704","host_type":"publisher"},{"url":"https://doaj.org/article/8407f70e2b904aacbb197bd392d154ec","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/12151469","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC12151469","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC12151469?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":[],"mesh_terms":["Intestines","Stem Cells","Animals","Humans","Drosophila melanogaster","Iron","Coenzyme A","Pantothenic Acid","Cell Proliferation","Aging","Homeostasis","Cellular Senescence"],"keywords":[],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"geo"},{"name":"gen"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-30T07:16:01.682151Z","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":[]}