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

Summary An epigenetic profile defining the DNA methylation age( DNAm age) of an individual has been suggested to be a biomarkerof aging, and thus possibly providing a tool for assessment of health and mortality. In this study, we estimated the DNAm ageof 378 Danish twins, age30–82 years, and furthermore included a 10-year longitudinal study of the 86 oldest-old twins (mean ageof 86.1 at follow-up), which subsequently were followed for mortality for 8 years. We found that the DNAm ageis highly correlated with chronological ageacross all agegroups (r = 0.97), but that the rate of change of DNAm agedecreases 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 agevs. chronological age. Furthermore, the intrapair twin analysis revealed a more-than-double mortality risk for the DNAmoldest 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 agedifference within twin pairs, thus showing a stronger association of DNAm agewith mortality in the oldest-old when controlling for familial factors. In conclusion, our results support that DNAm agequalifies as a biomarkerof aging.