title: DNA methylation age of blood predicts all-cause mortality in later life.
abstract: BACKGROUND
  DNA methylation levels change with age. Recent studies have identified biomarkers of chronological age based on DNA methylation levels. It is not yet known whether DNA methylation age captures aspects of biological age.
  
  
  RESULTS
  Here we test whether differences between people's chronological ages and estimated ages, DNA methylation age, predict all-cause mortality in later life. The difference between DNA methylation age and chronological age (Δage) was calculated in four longitudinal cohorts of older people. Meta-analysis of proportional hazards models from the four cohorts was used to determine the association between Δage and mortality. A 5-year higher Δage is associated with a 21% higher mortality risk, adjusting for age and sex. After further adjustments for childhood IQ, education, social class, hypertension, diabetes, cardiovascular disease, and APOE e4 status, there is a 16% increased mortality risk for those with a 5-year higher Δage. A pedigree-based heritability analysis of Δage was conducted in a separate cohort. The heritability of Δage was 0.43.
  
  
  CONCLUSIONS
  DNA methylation-derived measures of accelerated aging are heritable traits that predict mortality independently of health status, lifestyle factors, and known genetic factors.
authors: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, 7 George Square, Edinburgh, EH8 9JZ, UK. riccardo.marioni@ed.ac.uk.|Medical Genetics Section, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, UK. riccardo.marioni@ed.ac.uk.|Queensland Brain Institute, The University of Queensland, Brisbane, 4072, QLD, Australia. riccardo.marioni@ed.ac.uk.
authors: Riccardo E
authors: RE
authors: Marioni
authors: Queensland Brain Institute, The University of Queensland, Brisbane, 4072, QLD, Australia. s.shah1@uq.edu.au.|University of Queensland Diamantina Institute, Translational Research Institute, The University of Queensland, Brisbane, 4072, QLD, Australia. s.shah1@uq.edu.au.
authors: Sonia
authors: S
authors: Shah
authors: Queensland Brain Institute, The University of Queensland, Brisbane, 4072, QLD, Australia. a.mcrae@uq.edu.au.|University of Queensland Diamantina Institute, Translational Research Institute, The University of Queensland, Brisbane, 4072, QLD, Australia. a.mcrae@uq.edu.au.
authors: Allan F
authors: AF
authors: McRae
authors: The NHLBI's Framingham Heart Study, Framingham, MA, 01702, USA. brian.chen@nih.gov.|Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, MD, 01702, USA. brian.chen@nih.gov.
authors: Brian H
authors: BH
authors: Chen
authors: Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, 02115, USA. ecolicin@hsph.harvard.edu.
authors: Elena
authors: E
authors: Colicino
authors: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, 7 George Square, Edinburgh, EH8 9JZ, UK. Sarah.Harris@igmm.ed.ac.uk.|Medical Genetics Section, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, EH4 2XU, UK. Sarah.Harris@igmm.ed.ac.uk.
authors: Sarah E
authors: SE
authors: Harris
authors: Wellcome Trust Clinical Research Facility, University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh, EH4 2XU, UK. jgibson6@staffmail.ed.ac.uk.
authors: Jude
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authors: Queensland Institute of Medical Research Berghofer Medical Research Institute, Brisbane, 4029, QLD, Australia. Anjali.Henders@qimrberghofer.edu.au.
authors: Anjali K
authors: AK
authors: Henders
authors: Department of Psychology, University of Edinburgh, Edinburgh, EH8 9JZ, UK. paul.redmond@ed.ac.uk.
authors: Paul
authors: P
authors: Redmond
authors: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, 7 George Square, Edinburgh, EH8 9JZ, UK. simon.cox@ed.ac.uk.|Department of Psychology, University of Edinburgh, Edinburgh, EH8 9JZ, UK. simon.cox@ed.ac.uk.
authors: Simon R
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authors: Department of Psychology, University of Edinburgh, Edinburgh, EH8 9JZ, UK. Alison.Pattie@ed.ac.uk.
authors: Alison
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authors: Department of Psychology, University of Edinburgh, Edinburgh, EH8 9JZ, UK. janie.corley@ed.ac.uk.
authors: Janie
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authors: Wellcome Trust Clinical Research Facility, University of Edinburgh, Western General Hospital, Crewe Road, Edinburgh, EH4 2XU, UK. Lee.Murphy@ed.ac.uk.
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authors: Queensland Institute of Medical Research Berghofer Medical Research Institute, Brisbane, 4029, QLD, Australia. Nick.Martin@qimrberghofer.edu.au.
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authors: Queensland Institute of Medical Research Berghofer Medical Research Institute, Brisbane, 4029, QLD, Australia. Grant.Montgomery@qimrberghofer.edu.au.
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authors: Center for Epigenetics, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA. afeinberg@jhu.edu.|Departments of Medicine, Molecular Biology/Genetics, Oncology, and Biostatistics, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA. afeinberg@jhu.edu.
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authors: Center for Epigenetics, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA. dfallin@jhu.edu.|Department of Mental Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, 21205, USA. dfallin@jhu.edu.
authors: M Daniele
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authors: Center for Epigenetics, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA. mmulthaup@gmail.com.
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authors: Department of Mental Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, 21205, USA. andrew.jaffe@libd.org.|Lieber Institute for Brain Development, Baltimore, MD, 21205, USA. andrew.jaffe@libd.org.
authors: Andrew E
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authors: The NHLBI's Framingham Heart Study, Framingham, MA, 01702, USA. robyjoehanes@hsl.harvard.edu.|Harvard Medical School, Boston, MA, 02115, USA. robyjoehanes@hsl.harvard.edu.|Hebrew Senior Life, Boston, MA, 02131, USA. robyjoehanes@hsl.harvard.edu.
authors: Roby
authors: R
authors: Joehanes
authors: Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, 02115, USA. jschwrtz@hsph.harvard.edu.|Department of Epidemiology, Harvard T.H. Chan School of Public Health, 665 Huntington Ave, Boston, MA, 02115, USA. jschwrtz@hsph.harvard.edu.
authors: Joel
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authors: Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, 02115, USA. acjust@hsph.harvard.edu.
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authors: The NHLBI's Framingham Heart Study, Framingham, MA, 01702, USA. klunetta@bu.edu.|Department of Biostatistics, Boston University School of Public Health, Boston, MA, 02118, USA. klunetta@bu.edu.
authors: Kathryn L
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authors: Lunetta
authors: The NHLBI's Framingham Heart Study, Framingham, MA, 01702, USA. murabito@bu.edu.|Section of General Internal Medicine, Department of Medicine, Boston University School of Medicine, Boston, MA, 02118, USA. murabito@bu.edu.
authors: Joanne M
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authors: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, 7 George Square, Edinburgh, EH8 9JZ, UK. jstarr@staffmail.ed.ac.uk.|Alzheimer Scotland Dementia Research Centre, University of Edinburgh, Edinburgh, EH8 9JZ, UK. jstarr@staffmail.ed.ac.uk.
authors: John M
authors: JM
authors: Starr
authors: Human Genetics, Gonda Research Center, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, 90095-7088, USA. shorvath@mednet.ucla.edu.|Biostatistics, School of Public Health, University of California Los Angeles, Los Angeles, CA, 90095, USA. shorvath@mednet.ucla.edu.
authors: Steve
authors: S
authors: Horvath
authors: Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, 02115, USA. abaccare@hsph.harvard.edu.|Department of Epidemiology, Harvard T.H. Chan School of Public Health, 665 Huntington Ave, Boston, MA, 02115, USA. abaccare@hsph.harvard.edu.
authors: Andrea A
authors: AA
authors: Baccarelli
authors: The NHLBI's Framingham Heart Study, Framingham, MA, 01702, USA. levyd@nhlbi.nih.gov.|Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, MD, 01702, USA. levyd@nhlbi.nih.gov.
authors: Daniel
authors: D
authors: Levy
authors: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, 7 George Square, Edinburgh, EH8 9JZ, UK. peter.visscher@uq.edu.au.|Queensland Brain Institute, The University of Queensland, Brisbane, 4072, QLD, Australia. peter.visscher@uq.edu.au.|University of Queensland Diamantina Institute, Translational Research Institute, The University of Queensland, Brisbane, 4072, QLD, Australia. peter.visscher@uq.edu.au.
authors: Peter M
authors: PM
authors: Visscher
authors: Queensland Brain Institute, The University of Queensland, Brisbane, 4072, QLD, Australia. naomi.wray@uq.edu.au.
authors: Naomi R
authors: NR
authors: Wray
authors: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, 7 George Square, Edinburgh, EH8 9JZ, UK. i.deary@ed.ac.uk.|Department of Psychology, University of Edinburgh, Edinburgh, EH8 9JZ, UK. i.deary@ed.ac.uk.
authors: Ian J
authors: IJ
authors: Deary
mesh_terms: D000368:Aged; D000375:Aging / Q000235:genetics; D001769:Blood / Q000378:metabolism*; D002423:Cause of Death; D015331:Cohort Studies; D019175:DNA Methylation / Q000235:genetics*; D003710:Demography; D005260:Female; D006801:Humans; D040582:Inheritance Patterns / Q000235:genetics; D007958:Leukocyte Count; D008297:Male; D009026:Mortality; D012307:Risk Factors; D016019:Survival Analysis
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