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

Kuiper, Lieke M, Polinder-Bos, Harmke A, Bizzarri, Daniele, Vojinovic, Dina, Vallerga, Costanza L, Beekman, Marian, Dollé, Martijn E T, Ghanbari, Mohsen, Voortman, Trudy, Reinders, Marcel J T, Verschuren, W M Monique, Slagboom, P Eline, van den Akker, Erik B, van Meurs, Joyce B J·2023·The Journals of Gerontology: Series A
DOI 10.1093/gerona/glad137PMC PMC10562890

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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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Metadata

Authors
Kuiper, L. M., Polinder-Bos, H. A., Bizzarri, D., Vojinovic, D., Vallerga, C. L., Beekman, M., Dollé, M. E. T., Ghanbari, M., Voortman, T., Reinders, M. J. T., Verschuren, W. M. M., Slagboom, P. E., van den Akker, E. B., & van Meurs, J. B. J.
Venue
The Journals of Gerontology: Series A
Publisher
Oxford University Press (OUP)
Published
2023-06-12
Volume
78
Issue
10
Pages
1753-1762
ISSN
  • 1079-5006
  • 1758-535X
DOI
10.1093/gerona/glad137
PMC
PMC10562890
Cited by
92
References
10
Language
en
Licence
creativecommons.org/licenses/by-nc-nd/4.0/ (vor)
Funders
  • Erasmus Medical Center
  • Erasmus University Rotterdam
  • Netherlands Organization for the Health Research and Development
  • Research Institute for Disease in the Elderly
  • Ministry of Education, Culture, and Science
  • Ministry of Health, Welfare, and Sports
  • European Commission
  • Municipality of Rotterdam
  • European Union (FP7/2007–2011, 259679)
  • Innovation-Oriented Research Program on Genomics (IGE05007)
  • Centre for Medical Systems Biology
  • Netherlands Consortium for Healthy Ageing (050-060-810)
  • Netherlands Organization for Scientific Research
  • BBMRI-NL (NWO 184.021.007, 184.033.111)
  • VOILA (ZonMW 457001001)
  • Medical Delta
  • Dutch Research Council (09150161810095)
  • Ministry of Health, Welfare, and Sport (S/010003)

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