DNA Methylation Biomarkers in Aging and Age-Related Diseases

Abstract

Recent research efforts provided compelling evidence of genome-wide DNA methylation alterations in aging and age-related disease. It is currently well established that DNA methylation biomarkers can determine biological age of any tissue across the entire human lifespan, even during development. There is growing evidence suggesting epigenetic age acceleration to be strongly linked to common diseases or occurring in response to various environmental factors. DNA methylation based clocks are proposed as biomarkers of early disease risk as well as predictors of life expectancy and mortality. In this review, we will summarize key advances in epigenetic clocks and their potential application in precision health. We will also provide an overview of progresses in epigenetic biomarker discovery in Alzheimer's, type 2 diabetes, and cardiovascular disease. Furthermore, we will highlight the importance of prospective study designs to identify and confirm epigenetic biomarkers of disease.

Keywords: Alzheimer’s disease; DNA methylation; aging; biomarkers; cardiovascular diseases; diabetes; epigenetic clocks.

FIGURE 1

The growing number of epigenetic age clocks developed for both humans and mice, including the number of CpG sites comprising the age-prediction model, as well as the tissues in which age can be estimated.

FIGURE 2

Diseases and conditions associated with DNAm age acceleration in blood DNA where epigenetic clocks can be used as biomarkers of disease. We only display diseases/conditions where epigenetic age acceleration is observed in blood or other non-invasive tissues. We do not show correlations with glucose, insulin, HDL, and triglyceride levels as well as with blood pressure since these factors are biomarkers on their own.