Epigenetic and Metabolomic Biomarkers for Biological Age: A Comparative Analysis of Mortality and Frailty Risk.
Level 3 - non-randomized controlled study
Prospective cohort study
PubMed 37303208 · doi:10.1093/gerona/glad137
What was done
The authors compared multiple biological age markers in two prospective cohorts totaling 3,222 participants. They evaluated epigenetic clocks (DNAm Horvath, DNAm Hannum, DNAm Lin, DNAm epiTOC, DNAm PhenoAge, DNAm DunedinPoAm, DNAm GrimAge, and DNAm Zhang) alongside metabolomic markers (MetaboAge and MetaboHealth) to assess how well they reflect five frailty measures and predict all-cause mortality.
What was found
The abstract reports no specific numerical effect sizes, hazard ratios, or confidence intervals. Qualitatively, biomarkers trained on mortality and biophysiological data outperformed markers trained solely on chronological age. DNAm GrimAge and MetaboHealth demonstrated the strongest associations with frailty and mortality; these associations were mutually independent and remained independent of clinical geriatric frailty scores.
Why it matters
These findings indicate that epigenetic and metabolomic clocks capture complementary, non-overlapping dimensions of biological aging. Combining mortality-trained molecular biomarkers with traditional clinical assessments could improve risk stratification for frailty and death.
Limits
The abstract does not report numerical effect sizes, follow-up durations, or demographic details of the two cohorts. Because this is an observational study, residual confounding cannot be ruled out, and clinical utility in routine practice remains to be established.
Cited by
- supports First-generation epigenetic clocks trained to predict chronological age are less predictive of mortality risk after adjusting for chronological age than second-generation clocks like GrimAge or PhenoAge.