Journal
GENOME BIOLOGY
Volume 16, Issue -, Pages -Publisher
BIOMED CENTRAL LTD
DOI: 10.1186/s13059-015-0584-6
Keywords
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Funding
- UK's Biotechnology and Biological Sciences Research Council (BBSRC)
- Royal Society
- Chief Scientist Office of the Scottish Government
- Age UK (The Disconnected Mind project)
- Centre for Cognitive Ageing and Cognitive Epidemiology (Pilot Fund award)
- Age UK
- Wellcome Trust Institutional Strategic Support Fund
- University of Edinburgh
- University of Queensland
- BBSRC
- Medical Research Council (MRC)
- University of Edinburgh as part of the cross-council Lifelong Health and Wellbeing initiative [MR/K026992/1]
- National Health and Medical Research Council (NHMRC) [613608, APP496667, APP1010374, APP1046880]
- NHMRC Fellowships [613602]
- Australia Research Council (ARC) Future Fellowship [FT0991360]
- National Institutes of Health [N01-HC-25195]
- Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health
- Division of Intramural Research, National Heart, Lung, and Blood Institute
- Center for Information Technology, National Institutes of Health, Bethesda, MD, USA
- U.S. National Institute of Environmental Health Sciences (NIEHS) [R01ES015172, R01ES021733]
- Cooperative Studies Program/ERIC, US Department of Veterans Affairs
- US Department of Agriculture, Agricultural Research Service [53-K06-510]
- [R01AG029451]
- BBSRC [BB/F019394/1] Funding Source: UKRI
- MRC [G0700704] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/F019394/1] Funding Source: researchfish
- Chief Scientist Office [ETM/55, CZB/4/505] Funding Source: researchfish
- Medical Research Council [MR/K026992/1, G0700704] Funding Source: researchfish
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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 (Delta(age)) 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 Delta(age) and mortality. A 5-year higher Delta(age) 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 Delta(age). A pedigree-based heritability analysis of Delta(age) was conducted in a separate cohort. The heritability of Delta(age) 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.
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