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DNA methylation age of blood predicts all-cause mortality in later life
Open accessAbstract
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 (Δ 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 Δ age and mortality. A 5-year higher Δ 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 Δ age . A pedigree-based heritability analysis of Δ age was conducted in a separate cohort. The heritability of Δ 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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A gain of novel bivalent domains is observed in ageing cells.
“A gain of novel bivalent domains is observed in ageing cells 65,66 (Figure 2),”
From The roles of DNA, RNA and histone methylation in ageing and cancer (2019) · cites this paper as [65]
In ageing cells, a gain of novel bivalent domains is observed, mostly due to gains of repressive H3K27me3 marks on regions that were marked by the active histone modification H3K4me3 in young cells.
“In ageing cells, a gain of novel bivalent domains is observed, mostly due to gains of repressive H3K27me3 marks on regions that were marked by the active histone modification H3K4me3 in young cells 65,66 .”
From The roles of DNA, RNA and histone methylation in ageing and cancer (2019) · cites this paper as [65]
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Metadata
- Authors
- Marioni, R. E., Shah, S., McRae, A. F., Chen, B. H., Colicino, E., Harris, S. E., Gibson, J., Henders, A. K., Redmond, P., Cox, S. R., Pattie, A., Corley, J., Murphy, L., Martin, N. G., Montgomery, G. W., Feinberg, A. P., Fallin, M. D., Multhaup, M. L., Jaffe, A. E., Joehanes, R., Schwartz, J., Just, A. C., Lunetta, K. L., Murabito, J. M., Starr, J. M., Horvath, S., Baccarelli, A. A., Levy, D., Visscher, P. M., Wray, N. R., & Deary, I. J.
- Affiliations
- The University of Queensland (AU)
- Translational Research Institute (AU)
- National Institutes of Health (US)
- Harvard University (US)
- Institute of Genetics and Cancer (GB)
- Western General Hospital (GB)
- QIMR Berghofer Medical Research Institute (AU)
- University of Edinburgh (GB)
- Johns Hopkins University (US)
- Boston University (US)
- Alzheimer Scotland (GB)
- University of California, Los Angeles (US)
- Corresponding author
- Wray, Naomi R
- Deary, Ian J
- ORCID
- Marioni, Riccardo E
- Shah, Sonia
- McRae, Allan F
- Chen, Brian H
- Colicino, Elena
- Harris, Sarah E
- Gibson, Jude
- Henders, Anjali K
- Redmond, Paul
- Corley, Janie
- Murphy, Lee
- Martin, Nicholas G
- Montgomery, Grant W
- Feinberg, Andrew P
- Fallin, M Daniele
- Jaffe, Andrew E
- Joehanes, Roby
- Schwartz, Joel
- Just, Allan C
- Lunetta, Kathryn L
- Murabito, Joanne M
- Starr, John M
- Horvath, Steve
- Baccarelli, Andrea A
- Levy, Daniel
- Visscher, Peter M
- Wray, Naomi R
- Deary, Ian J
- Venue
- Genome Biology
- Published
- 2015-01-30
- Volume
- 16
- Issue
- 1
- Pages
- 25-25
- ISSN
- 1465-6906 (ISSN-L)
- PMC
- PMC4350614
- OpenAlex
- W2159536887
- Cited by
- 1,261
- References
- 50
- Citations by year
- 2026: 63 · 2025: 118 · 2024: 117 · 2023: 116 · 2022: 121 · 2021: 131 · 2020: 128 · 2019: 110 · 2018: 126 · 2017: 113 · 2016: 79 · 2015: 37
- FWCI
- 51.41
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Genome biology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- UCL Discovery (University College London) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, cc-by)
- Funders
- U.S. Department of Agriculture (53‐K06‐5‐10)
- U.S. Department of Veterans Affairs
- Wellcome Trust
- Scottish Government
- Royal Society
- Age UK (MR/K026992/1)
- University of Edinburgh (MR/K026992/1)
- University of Queensland
- Centre for Cognitive Ageing and Cognitive Epidemiology (MR/K026992/1)
- National Institutes of Health (n01hc25195-41-0-1, N01-HC 25195)
- Directorate for Biological Sciences
- Agricultural Research Service (53-K06-510)
- Medical Research Council (MR/K026992/1)
- Biotechnology and Biological Sciences Research Council (MR/K026992/1, BB/F019394/1)
- Australian Research Council (FT0991360)
- National Health and Medical Research Council (496667, 1010374, 613602, 613608, 1046880)
- National Institute on Aging (R01AG029451, R01AG042187)
- National Heart, Lung, and Blood Institute (N01‐HC25195, N01-HC-025195)
- National Institute of General Medical Sciences (T32GM007445)
- National Institute of Environmental Health Sciences (R01ES021733, R01ES015172, R01ES020268)
- Center for Information Technology
- NHLBI Division of Intramural Research
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- DNA methylation age, epigenetic clocks, biological age, accelerated aging, all-cause mortality, older adults, heritability, chronological age, mortality prediction, APOE ε4
- MeSH terms
- Aged, Aging, Blood, Cause of Death, Demography, Female, Humans, Leukocyte Count, Male, Mortality, Risk Factors, Cohort Studies, Survival Analysis, DNA Methylation, Inheritance Patterns
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