DNA methylation age of blood predicts all-cause mortality in later life

By R. Marioni, Sonia H. Shah, A. McRae, Brian H. Chen, E. Colicino, S. Harris, J. Gibson, A. Henders, Paul Redmond, S. Cox and 21 more. Genome Biology, 2015

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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. 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. DNA methylation-derived measures of accelerated aging are heritable traits that predict mortality independently of health status, lifestyle factors, and known genetic factors.

Subfields: Genetics, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/5c69e7d2afa5881cb543c6ff19dcaa4bfbf8cd54

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Epigenetic clock analysis of diet, exercise, education, and lifestyle factors (2017, positive): “For instance, the epigenetic age of blood has been found to be predictive of all-cause mortality [40-43], frailty [44], lung cancer [45], and cognitive and physical functioning [46], while the blood of the offspring of Italian semi-supercentenarians (i.”
Measuring biological aging in humans: A quest (2019, background): “In some studies, older epigenetic age has been associated with biomarkers of inflammation, as well as physical and cognitive function (Degerman et al., 2017; Gale et al., 2018; Levine et al., 2018; Ligthart et al., 2016; Marioni et al., 2015; Quach et al., 2017; Spiegel, Sewal, & Rapp, 2014).”
DNA methylation and healthy human aging (2015, background): “…predict health outcomes for those in the epigenetically old or epigenetically young groups relative to those who display concordant epigenetic and chronological ages, supported by a very recent study which associated accelerated epigenetic age with increased mortality (Marioni et al., 2015) (Fig.”
An epigenetic clock analysis of race/ethnicity, sex, and coronary heart disease (2016, background): “[23] show that DNAm age adjusted for blood cell counts (i.”
DNA methylation-based measures of biological age: meta-analysis predicting time to death (2016, methodology): “We used an epigenetic biomarker of age based on 353 CpG markers as one measure of epigenetic age because: a) it is an accurate measurement of age across multiple tissues [3]; b) we previously showed that it is predictive of all-cause mortality [5]; c) it correlated with measures of cognitive/physica”
The Continuum of Aging and Age-Related Diseases: Common Mechanisms but Different Rates (2018, background): “In many different studies, Horvath’s clock has proven to grasp features of accelerated aging in many different age-related clinical conditions such as cancer (237, 238), neurodegeneration (239–241), progeroid genetic syndromes other than DS, such as Werner syndrome (242), and all-cause mortality (24”
DNA methylation aging clocks: challenges and recommendations (2019, background): “Age acceleration, defined as the difference between this epigenetically measured age and the actual chronological age, was associated with mortality [26] and other age-related phenotypes or diseases [32–39].”
An epigenetic biomarker of aging for lifespan and healthspan (2018, background): “2, the DNAm age based measures from Hannum and Horvath also related to all-cause mortality, consistent with what has been reported previously [15, 19, 23, 33, 34].”