DNA Methylation Clocks in Age-related Disease: The New Molecular and Medical Genetics

DNA methylation biomarkers of aging, termed “epigenetic clocks” enable an estimate of biological age across various tissues, and reflect an individuals’ aging trajectory. They also permit the identification of individuals with accelerated epigenetic aging compared to their chronological age. The first generation of epigenetic clocks, based on DNA methylation at a number of sites across the genome, include a blood-specific clock and a multi-tissue predictor. They were considered some of the strongest aging biomarkers and could predict longevity and mortality risk. The second generation clocks, developed more recently, incorporate estimates of specific proteomic measures, and were developed to have better predictive capacity for age-related diseases, including frailty, cancer, diabetes, cardiovascular diseases, and dementia. More recent clock iterations have also been developed specifically for certain diseases. Lifestyle and environmental factors have been shown to influence epigenetic age and given that they are modifiable, hold promise for their potential to alter the aging trajectory.