Accelerated Epigenetic Age and Cardiovascular Risk Factors

Epigenetic patterns determine the behavior of a cell, and change constantly in response to cell state and the surrounding tissue environment. Epigenetic state can be used to measure biological age, the epigenetic clock. When an epigenetic clock indicates an age older than chronological age, that is referred to as epigenetic age acceleration. While the clocks are not fully understood in detail, it is thought that the specific epigenetic changes measured are reflective of the burden of cell and tissue damage and dysfunction that causes aging. This acceleration has been shown to correlate with risk and status of a number of age-related conditions.

In today's open access paper, researchers compare epigenetic age acceleration with cardiovascular risk factors. Their point of view is that epigenetic aging, and specifically increased DNA methylation, is a cause rather than a consequence of dysfunction. The work on epigenetic reprogramming of the past few years is supportive of this view that epigenetic change produces significant downstream consequences in aging: reprogramming the epigenetics of old cells does appear to produce some degree of rejuvenation in cells, tissues, and animals. It may be quite close to the root causes of aging, if the work showing it to be a direct consequence of DNA double strand break repair continues to hold up. This is not supportive of the idea that increased DNA methylation is generally a bad thing, however, or that blanket reductions in DNA methylation will be a good basis for therapy.

Accelerated DNA methylation age plays a role in the impact of cardiovascular risk factors on the human heart

DNA methylation (DNAm) age acceleration (AgeAccel) and cardiac age by 12-lead advanced electrocardiography (A-ECG) are promising biomarkers of biological and cardiac aging, respectively. We aimed to explore the relationships between DNAm age and A-ECG heart age and to understand the extent to which DNAm AgeAccel relates to cardiovascular (CV) risk factors in a British birth cohort from 1946.

We studied four DNAm ages (AgeHannum, AgeHorvath, PhenoAge, and GrimAge) and their corresponding AgeAccel. Outcomes were the results from two publicly available ECG-based cardiac age scores: a Bayesian A-ECG-based heart age score and a deep neural network (DNN) ECG-based heart age score. DNAm AgeAccel was also studied relative to results from two logistic regression-based A-ECG disease scores, one for left ventricular (LV) systolic dysfunction (LVSD), and one for LV electrical remodeling (LVER). Generalized linear models were used to explore the extent to which any associations between biological cardiometabolic risk factors (body mass index, hypertension, diabetes, high cholesterol, previous cardiovascular disease [CVD], and any CV risk factor) and the ECG-based outcomes are mediated by DNAm AgeAccel.

By the age of 60, participants with accelerated DNA methylation appear to have older, weaker, and more electrically impaired hearts. We show that the harmful effects of CV risk factors on cardiac age and health, appear to be partially mediated by DNAm AgeAccelPheno and AgeAccelGrim. This highlights the need to further investigate the potential cardioprotective effects of selective DNA methyltransferases modulators.