Epigenetic age acceleration predicts cancer, cardiovascular, and all-cause mortality in a German case cohort

Background Previous studies have developed models predicting methylation age from DNA methylation in blood and other tissues (epigenetic clock) and suggested the difference between DNA methylation and chronological ages as a marker of healthy aging. The goal of this study was to confirm and expand s...

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Veröffentlicht in:Clinical epigenetics Jg. 8; H. 1; S. 64
Hauptverfasser: Perna, Laura, Zhang, Yan, Mons, Ute, Holleczek, Bernd, Saum, Kai-Uwe, Brenner, Hermann
Format: Journal Article
Sprache:Englisch
Veröffentlicht: London BioMed Central 03.06.2016
BioMed Central Ltd
Springer Nature B.V
Schlagworte:
Aged
Aging
Aging (Biology)
Aging - genetics
Biomedical and Life Sciences
Biomedicine
Biorhythms
Blood - metabolism
Cardiovascular Diseases - genetics
Cause of Death
Cohort Studies
development
Disease susceptibility
Epigenesis, Genetic
Epigenetic inheritance
Female
Gene Function
Genetic aspects
Health aspects
Human Genetics
Humans
imprinting and reproductive epigenetics
Leukocyte Count
Male
Middle Aged
Mortality
Neoplasms - genetics
Proportional Hazards Models
Risk Factors
Germany
Epigenetic clock
DNA methylation age
Mortality risk
Epigenetic age acceleration
ISSN:1868-7075, 1868-7083, 1868-7083, 1868-7075
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Zusammenfassung:Background Previous studies have developed models predicting methylation age from DNA methylation in blood and other tissues (epigenetic clock) and suggested the difference between DNA methylation and chronological ages as a marker of healthy aging. The goal of this study was to confirm and expand such observations by investigating whether different concepts of the epigenetic clocks in a population-based cohort are associated with cancer, cardiovascular, and all-cause mortality. Results DNA methylation age was estimated in a cohort of 1863 older people, and the difference between age predicted by DNA methylation and chronological age (Δ age ) was calculated. A case-cohort design and weighted proportional Cox hazard models were used to estimate associations of Δ age with cancer, cardiovascular, and all-cause mortality. Hazard ratios for Δ age (per 5 years) calculated using the epigenetic clock developed by Horvath were 1.23 (95 % CI 1.10–1.38) for all-cause mortality, 1.22 (95 % CI 1.03–1.45) for cancer mortality, and 1.19 (95 % CI 0.98–1.43) for cardiovascular mortality after adjustment for batch effects, age, sex, educational level, history of chronic diseases, hypertension, smoking status, body mass index, and leucocyte distribution. Associations were similar but weaker for Δ age calculated using the epigenetic clock developed by Hannum. Conclusions These results show that age acceleration in terms of the difference between age predicted by DNA methylation and chronological age is an independent predictor of all-cause and cause-specific mortality and may be useful as a general marker of healthy aging.
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ISSN:1868-7075
1868-7083
1868-7083
1868-7075
DOI:10.1186/s13148-016-0228-z