title: DNA methylation age is associated with mortality in a longitudinal Danish twin study.
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.
authors.affiliation: The Danish Aging Research Center, and The Danish twin Registry, Institute of Public Health, University of Southern Denmark, Odense, Denmark.
authors.forename: Lene
authors.initials: L
authors.lastname: Christiansen
authors.affiliation: Max Planck Odense Center on the Biodemography of Aging, Institute of Public Health, University of Southern Denmark, Odense, Denmark.
authors.forename: Adam
authors.initials: A
authors.lastname: Lenart
authors.affiliation: The Danish Aging Research Center, and The Danish twin Registry, Institute of Public Health, University of Southern Denmark, Odense, Denmark.|Department of Clinical Genetics, Odense University Hospital, Odense, Denmark.
authors.forename: Qihua
authors.initials: Q
authors.lastname: Tan
authors.affiliation: Max Planck Odense Center on the Biodemography of Aging, Institute of Public Health, University of Southern Denmark, Odense, Denmark.|Max Planck Institute for Demographic Research, Rostock, Germany.
authors.forename: James W
authors.initials: JW
authors.lastname: Vaupel
authors.affiliation: The Center for Human Development and Aging, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, NJ, USA.
authors.forename: Abraham
authors.initials: A
authors.lastname: Aviv
authors.affiliation: The Danish Aging Research Center, and The Danish twin Registry, Institute of Public Health, University of Southern Denmark, Odense, Denmark.|Department of Psychology, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Matt
authors.initials: M
authors.lastname: McGue
authors.affiliation: The Danish Aging Research Center, and The Danish twin Registry, Institute of Public Health, University of Southern Denmark, Odense, Denmark.|Department of Clinical Genetics, Odense University Hospital, Odense, Denmark.|Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense, Denmark.
authors.forename: Kaare
authors.initials: K
authors.lastname: Christensen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics*; D003718:Denmark; D044127:Epigenesis, Genetic / Q000235:genetics*; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009026:Mortality
keywords: DNA methylation; biological age; biomarker; epigenetic clock; mortality; twins