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

Overview

Journal J Gerontol A Biol Sci Med Sci

Specialty Geriatrics

Date 2023 Jun 12

PMID 37303208

Authors

Lieke M Kuiper

Harmke A Polinder-Bos

Daniele Bizzarri

Dina Vojinovic

Costanza L Vallerga

Marian Beekman

E T Dolle

Mohsen Ghanbari

Trudy Voortman

Marcel J T Reinders

W M Monique Verschuren

P Eline Slagboom

Erik B van den Akker

Joyce B J van Meurs

Affiliations

Soon will be listed here.

Abstract

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.

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