Year: 2025
Type: article
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.
Source: npj Aging
Authors: Dantong Zhu, Judy Z. Wu, Patrick T. Griffin, Brady A. Samuelson, David A. Sinclair, Alice E. Kane
Language: English
Topic: Frailty in Older Adults
Subfield: Geriatrics and Gerontology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,690
Awards: Role of epigenetic decay in cell senescence and aging, Tagmentation-based Indexing for Methylation Sequencing as a novel method of high-throughput methylation clock measurement, Development of a Predictive Frailty Clock & Longitudinal Investigation of its Epigenetic Determinants, A novel method to identify regulators of biological aging
based on high-throughput sequencing of epigenetic clocks.
OpenAlex ID: W4410621365