DNA methylation age is associated with mortality in a longitudinal Danish twin study

Lene Christiansen, Adam Lenart, Qihua Tan, James W. Vaupel, Abraham Aviv, Matt Mcgue, Kaare Christensen

Research output: Contribution to journalArticle

126 Scopus citations

Abstract

An epigenetic profile defining the DNA methylation age (DNAm age) of an individual has been suggested to be a biomarker of aging, and thus possibly providing a tool for assessment of health and mortality. In this study, we estimated the DNAm age of 378 Danish twins, age 30-82 years, and furthermore included a 10-year longitudinal study of the 86 oldest-old twins (mean age of 86.1 at follow-up), which subsequently were followed for mortality for 8 years. We found that the DNAm age is highly correlated with chronological age across all age groups (r = 0.97), but that the rate of change of DNAm age decreases with age. The results may in part be explained by selective mortality of those with a high DNAm age. This hypothesis was supported by a classical survival analysis showing a 35% (4-77%) increased mortality risk for each 5-year increase in the DNAm age vs. chronological age. Furthermore, the intrapair twin analysis revealed a more-than-double mortality risk for the DNAm oldest twin compared to the co-twin and a 'dose-response pattern' with the odds of dying first increasing 3.2 (1.05-10.1) times per 5-year DNAm age difference within twin pairs, thus showing a stronger association of DNAm age with mortality in the oldest-old when controlling for familial factors. In conclusion, our results support that DNAm age qualifies as a biomarker of aging.

Original languageEnglish (US)
Pages (from-to)149-154
Number of pages6
JournalAging cell
Volume15
Issue number1
DOIs
StatePublished - Feb 1 2016

All Science Journal Classification (ASJC) codes

  • Aging
  • Cell Biology

Keywords

  • Biological age
  • Biomarker
  • DNA methylation
  • Epigenetic clock
  • Mortality
  • Twins

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  • Cite this

    Christiansen, L., Lenart, A., Tan, Q., Vaupel, J. W., Aviv, A., Mcgue, M., & Christensen, K. (2016). DNA methylation age is associated with mortality in a longitudinal Danish twin study. Aging cell, 15(1), 149-154. https://doi.org/10.1111/acel.12421