TY - JOUR
T1 - Epigenetic and Metabolomic Biomarkers for Biological Age
T2 - A Comparative Analysis of Mortality and Frailty Risk
AU - Kuiper, Lieke M
AU - Polinder-Bos, Harmke A
AU - Bizzarri, Daniele
AU - Vojinovic, Dina
AU - Vallerga, Costanza L
AU - Beekman, Marian
AU - Dollé, E T
AU - Ghanbari, Mohsen
AU - Voortman, Trudy
AU - Reinders, Marcel J T
AU - Verschuren, W M Monique
AU - Slagboom, P Eline
AU - van den Akker, Erik B
AU - van Meurs, Joyce B J
N1 - Publisher Copyright:
© The Author(s) 2023. Published by Oxford University Press on behalf of The Gerontological Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (https:// creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited.
PY - 2023/10/9
Y1 - 2023/10/9
N2 - 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.
AB - 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.
KW - Aged
KW - Aging/genetics
KW - Biomarkers
KW - DNA Methylation
KW - Epigenesis, Genetic
KW - Frailty/genetics
KW - Humans
KW - Prospective Studies
UR - http://www.scopus.com/inward/record.url?scp=85173583279&partnerID=8YFLogxK
U2 - 10.1093/gerona/glad137
DO - 10.1093/gerona/glad137
M3 - Article
C2 - 37303208
SN - 1079-5006
VL - 78
SP - 1753
EP - 1762
JO - Journals of Gerontology Series A-Biological Sciences and Medical Sciences
JF - Journals of Gerontology Series A-Biological Sciences and Medical Sciences
IS - 10
ER -