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

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          Summary

          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.

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          Author and article information

          Journal
          Aging Cell
          Aging Cell
          10.1111/(ISSN)1474-9726
          ACEL
          Aging Cell
          John Wiley and Sons Inc. (Hoboken )
          1474-9718
          1474-9726
          17 November 2015
          February 2016
          : 15
          : 1 ( doiID: 10.1111/acel.2016.15.issue-1 )
          : 149-154
          Affiliations
          [ 1 ] The Danish Aging Research Center, and The Danish twin Registry Institute of Public HealthUniversity of Southern Denmark OdenseDenmark
          [ 2 ] Max Planck Odense Center on the Biodemography of Aging Institute of Public HealthUniversity of Southern Denmark OdenseDenmark
          [ 3 ] Department of Clinical GeneticsOdense University Hospital OdenseDenmark
          [ 4 ]Max Planck Institute for Demographic Research RostockGermany
          [ 5 ] The Center for Human Development and Aging New Jersey Medical SchoolUniversity of Medicine and Dentistry of New Jersey Newark NJUSA
          [ 6 ] Department of PsychologyUniversity of Minnesota Minneapolis MNUSA
          [ 7 ] Department of Clinical Biochemistry and PharmacologyOdense University Hospital OdenseDenmark
          Author notes
          [*] [* ] Correspondence

          Lene Christiansen, Epidemiology, Biostatistics and Biodemography, The Danish Aging Research Center, and The Danish Twin Registry, Department of Public Health, University of Southern Denmark, J.B. Winsloews Vej 9B, 5000 Odense C, Denmark. Tel.: +45 65503378; e‐mail : lchristiansen@ 123456health.sdu.dk

          Article
          ACEL12421
          10.1111/acel.12421
          4717264
          26594032
          aee27889-8fed-4e11-a2dd-1c343ac3813e
          © 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

          This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

          History
          : 11 October 2015
          Page count
          Pages: 6
          Funding
          Funded by: European Union's Seventh Framework Programme
          Award ID: FP7/2007‐2011
          Award ID: 259679
          Funded by: The Danish National Program for Research Infrastructure 2007
          Award ID: 09‐063256
          Categories
          Original Article
          Original Articles
          Custom metadata
          2.0
          acel12421
          February 2016
          Converter:WILEY_ML3GV2_TO_NLMPMC version:4.7.5 mode:remove_FC converted:19.01.2016

          Cell biology
          biological age,biomarker,dna methylation,epigenetic clock,mortality,twins
          Cell biology
          biological age, biomarker, dna methylation, epigenetic clock, mortality, twins

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