Author Insight: DNA Methylation-based Measures of Biological Age



January 4, 2022

Aging-US published "DNA methylation-based measures of biological age: meta-analysis predicting time to death" in 2016, which reported that estimates of biological age based on DNA methylation patterns, often referred to as "epigenetic age", "DNAm age", have been shown to be robust biomarkers of age in humans. These authors previously demonstrated that independent of chronological age, epigenetic age assessed in blood predicted all-cause mortality in four human cohorts. Here, they expanded their original observation to 13 different cohorts for a total sample size of 13,089 individuals, including three racial/ethnic groups. In addition, they examined whether incorporating information on blood cell composition into the epigenetic age metrics improves their predictive power for mortality. All considered measures of epigenetic age acceleration were predictive of mortality, independent of chronological age, even after adjusting for additional risk factors. The authors said, "DNA methylation-based biomarkers, often referred to as ‘epigenetic age’ or ‘epigenetic clock’, are robust estimators of chronological age of an individual." This estimate is consistent across most types of biological specimens, including whole blood, brain, breast, kidney, liver, lung, and saliva and cell types, including CD4 T cells, monocytes, B cells, glial cells, and neurons. It is well known that blood cell composition changes with age and some of these changes might be independent predictors of mortality. Thus, it is of interest to understand whether considering information on blood cell composition in measures of epigenetic age improves their predictive power for mortality. Here, the authors evaluated the ability to predict time to death for blood-based epigenetic age measures, both published and novel measures that incorporate information on blood cell composition. Due to the well documented age-related changes in blood cell composition, they were able to distinguish epigenetic measures of age that were independent of changes in blood cell composition, and measures that incorporated age-related changes in blood cell composition. The Research Team concluded in their Aging-US Research Output, "our results inform the ongoing debate about whether epigenetic biomarkers of age capture an aspect of biological age. While epigenetic processes are unlikely to be the only mediators of chronological age on mortality—in fact, multiple risk factors have stronger effects on mortality—our results suggest that at least one of the mediating processes relates to the epigenetic age of blood tissue and that this process is independent of age-dependent changes in blood cell composition. Future studies will be useful for gaining a mechanistic understanding of this intrinsic epigenetic aging process." Full Text - Correspondence to: Steve Horvath email: Keywords: all-cause mortality, lifespan, epigenetics, epigenetic clock, DNA+methylation, mortality About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at​​ or connect with us on: SoundCloud - Facebook - Twitter - Instagram - YouTube -​ LinkedIn - Pinterest - Aging-US is published by Impact Journals, LLC please visit​​ or connect with @ImpactJrnls Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

Cell ScienceGenomicsMolecular BiologyNeuroscience

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