{"doi":"10.1038/s41514-025-00237-w","title":"Metabolomics biomarkers of frailty: a longitudinal study of aging female and male mice","abstract":"Frailty is an age-related geriatric syndrome. We performed a longitudinal study of aging female (n = 40) and male (n = 47) C57BL/6NIA mice, measured frailty index and derived metabolomics data from plasma. We identify age-related differentially abundant metabolites, determine frailty-related metabolites, and generate frailty features, both in the whole cohort and sex-stratified subgroups. Using the features, we perform an association study and build a metabolomics-based frailty clock. We find that frailty-related metabolites are enriched for amino acid metabolism and metabolism of cofactors and vitamins, include ergothioneine, tryptophan and alpha-ketoglutarate, and present sex dimorphism. We identify B vitamin metabolism related flavin-adenine dinucleotide and pyridoxate as female-specific frailty biomarkers, and lipid metabolism related sphingomyelins, glycerophosphoethanolamine and glycerophosphocholine as male-specific frailty biomarkers. These associations are confirmed in a validation cohort, with ergothioneine and perfluorooctanesulfonate identified as robust frailty biomarkers. Our results identify sex-specific metabolite frailty biomarkers, and shed light on potential mechanisms.","journal":"npj Aging","year":2025,"id":525812,"datarank":0.20794415416798362,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"self_citation_contribution":0.20794415416798362,"citation_network_contribution":0.0,"self_endowment_contribution":0.20794415416798362,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":2,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.808,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":740903,"name":"Judy Wu","orcid":"0000-0001-7040-4420","position":1,"is_corresponding":false},{"id":806986,"name":"Patrick Griffin","orcid":"0000-0002-8241-7381","position":2,"is_corresponding":false},{"id":1229136,"name":"Brady Samuelson","orcid":null,"position":3,"is_corresponding":false},{"id":106661,"name":"David Sinclair","orcid":"0000-0002-9936-436X","position":4,"is_corresponding":false},{"id":218499,"name":"Alice E. Kane","orcid":"0000-0002-4303-0491","position":5,"is_corresponding":false},{"id":1400930,"name":"Dantong Zhu","orcid":"0000-0003-0875-0490","position":0,"is_corresponding":true}],"reference_count":70,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:50:25.860105Z","pmid":"40410187","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":[]}