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

Abstract

BackgroundPrevious 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.ResultsDNA methylation age was estimated in a cohort of 1863 older people, and the difference between age predicted by DNA methylation and chronological age (Δage) was calculated. A case-cohort design and weighted proportional Cox hazard models were used to estimate associations of Δage with cancer, cardiovascular, and all-cause mortality. Hazard ratios for Δage (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 Δage calculated using the epigenetic clock developed by Hannum.ConclusionsThese 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13148-016-0228-z) contains supplementary material, which is available to authorized users.

Associations between long-term exposure to PM2.5 component species and blood DNA methylation age in the elderly: The VA normative aging study

“…For instance, both Horvath and Hannum DNAm-age appear to be useful in predicting mortality (Chen et al, 2016; Wolf et al, 2016). However, in a study of male and female veterans, Hannum DNAm-age was associated with post-traumatic stress disorder and neural integrity, but Horvath DNAm-age was not (Perna et al, 2016). The differences in these two DNAm-age measures may stem from the fact that they are derived from almost entirely different CpG sites or from the fact that Horvath DNAm-age was constructed using many datasets of multiple tissue types and the Hannum DNAm-age was based only on blood from one dataset (Horvath, 2013; Hannum et al, 2013).…”

Plasma proteomic signature of age in healthy humans

“…The “epigenetic clock,” a biomarker index that combines weighted information of a subset of DNA methylation sites raised great interest because it is both strongly associated with chronological age across multiple tissues and populations and independent of age, predicts multiple health outcomes, including cardiovascular disease, cancer, and mortality (Chen et al., 2016; Levine et al., 2015; Perna et al., 2016). These findings suggest that aging is associated with stereotyped and reproducible molecular changes that can potentially be used to identify individuals who are aging faster or slower than the average population.…”

Dynamics of epigenetic age following hematopoietic stem cell transplantation

“…The "epigenetic clock" is thought to capture aspects of biological age, supported by data demonstrating that older epigenetic age of blood is predictive of all-cause mortality. 13,14 A detailed review of the literature describing the utility of the "epigenetic clock" is listed in the Online Supplementary Appendix. It is not yet known whether the "epigenetic clock" method is useful in the context of allogeneic HSCT.…”