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DNA methylation plays a critical role in gene expression regulation and has emerged as a robust biomarker of biological age. This modification will become heavier or site drift along with aging. Recently, it is termed epigenetic clocks-such as Horvath, Hannum, PhenoAge, and GrimAge-leverage specific methylation patterns to accurately predict age-related decline, disease risk, and mortality. These tools are now widely applied across diverse tissues, populations, and disease contexts. Beyond age-related loss of methylation control, accelerated DNA methylation age has been linked to environmental exposures, lifestyle factors, and chronic diseases, further reinforcing its value as a dynamic and clinically relevant marker of biological aging. DNA methylation is reshaping our understanding of aging and disease risk, with promising implications for preventive medicine and interventions aimed at promoting healthy longevity. However, it must be admitted that some challenges remain, including limited generalizability across populations, an unclear mechanism, and inconsistent longitudinal performance. In this review, we examine the biological foundations of DNA methylation, major advances in epigenetic clock development, and their expanding applications in aging research, disease prediction and health monitoring.
Chen et al. (Mon,) studied this question.