Epigenetic and Metabolomic Biomarkers for Biological Age: A Comparative Analysis of Mortality and Frailty Risk

Lieke M. Kuiper, Harmke A. Polinder-Bos, Daniele Bizzarri, Dina Vojinovic, Costanza L. Vallerga, Marcel J.T. Reinders, P. Eline Slagboom, Erik B. van den Akker, More Authors

Research output: Contribution to journalArticleScientificpeer-review

4 Citations (Scopus)
29 Downloads (Pure)


Biological age captures a person's age-related risk of unfavorable outcomes using biophysiological information. Multivariate biological age measures include frailty scores and molecular biomarkers. These measures are often studied in isolation, but here we present a large-scale study comparing them. In 2 prospective cohorts (n = 3 222), we compared epigenetic (DNAm Horvath, DNAm Hannum, DNAm Lin, DNAm epiTOC, DNAm PhenoAge, DNAm DunedinPoAm, DNAm GrimAge, and DNAm Zhang) and metabolomic-based (MetaboAge and MetaboHealth) biomarkers in reflection of biological age, as represented by 5 frailty measures and overall mortality. Biomarkers trained on outcomes with biophysiological and/or mortality information outperformed age-trained biomarkers in frailty reflection and mortality prediction. DNAm GrimAge and MetaboHealth, trained on mortality, showed the strongest association with these outcomes. The associations of DNAm GrimAge and MetaboHealth with frailty and mortality were independent of each other and of the frailty score mimicking clinical geriatric assessment. Epigenetic, metabolomic, and clinical biological age markers seem to capture different aspects of aging. These findings suggest that mortality-trained molecular markers may provide novel phenotype reflecting biological age and strengthen current clinical geriatric health and well-being assessment.

Original languageEnglish
Pages (from-to)1753-1762
Number of pages10
JournalThe journals of gerontology. Series A, Biological sciences and medical sciences
Issue number10
Publication statusPublished - 2023


  • DNA methylation
  • Frailty
  • Mortality


Dive into the research topics of 'Epigenetic and Metabolomic Biomarkers for Biological Age: A Comparative Analysis of Mortality and Frailty Risk'. Together they form a unique fingerprint.

Cite this