Dynamic DNA Methylation During Aging: A "Prophet" of Age-Related Outcomes

The biological markers of aging used to predict physical health status in older people are of great interest. Telomere shortening, which occurs during the process of cell replication, was initially considered a promising biomarker for the prediction of age and age-related outcomes (e.g., diseases, longevity). However, the high instability in detection and low correlation with age-related outcomes limit the extension of telomere length to the field of prediction. Currently, a growing number of studies have shown that dynamic DNA methylation throughout human lifetime exhibits strong correlation with age and age-related outcomes. Indeed, many researchers have built age prediction models with high accuracy based on age-dependent methylation changes in certain CpG loci. For now, DNA methylation based on epigenetic clocks, namely epigenetic or DNA methylation age, serves as a new standard to track chronological age and predict biological age. Measures of age acceleration (Δage, DNA methylation age - chronological age) have been developed to assess the health status of a person. In addition, there is evidence that an accelerated epigenetic age exists in patients with certain age-related diseases (e.g., Alzheimer's disease, cardiovascular disease). In this review, we provide an overview of the dynamic signatures of DNA methylation during aging and emphasize its practical utility in the prediction of various age-related outcomes.