Journal Article Preprint Epublish
PubMed: 39896479 DOI: 10.1101/2025.01.22.634160
Metabolomics biomarkers of frailty: a longitudinal study of aging female and male mice.
bioRxiv
Authors: Dantong Zhu, Judy Z Wu, Patrick Griffin, Brady A Samuelson, David A Sinclair, Alice E Kane
Affiliations
- Institute for Systems Biology, Seattle, WA 98109, USA.
- Blavatnik Institute, Department of Genetics, Paul F. Glenn Center for Biology of Aging Research at Harvard Medical School, Boston, MA 02115, USA.
- Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA 98195, USA.
Abstract
Frailty is an age-related geriatric syndrome, for which the mechanisms remain largely unknown. 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 samples. We identify differentially abundant metabolites related to aging, determine frailty related metabolites via a machine learning approach, and generate a union set of frailty features, both in the whole cohort and in 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. In summary, our results identify sex-specific metabolite biomarkers of frailty in aging, and shed light on potential mechanisms involved in frailty.
MeSH
Longitudinal Studies, Vitamins, Ergothioneine, Aging, Biomarkers, Metabolomics, Sex Characteristics, Sex, Frailty, Sex Differences