Population Epigenomics and Aging

Abstract

The epigenome has memory functions, since it is able to preserve the results of cellular perturbations by environmental factors in form of changes in DNA methylation, histone modifications or 3D organization of chromatin. Such epigenetic drifts can be detected in epigenomic patterns, like in DNA methylation maps, that are heritable from parent to daughter cells and may in part even be transferred to the next generation. The concept of transgenerational epigenetic inheritance could explain how lifestyle factors of parents and grandparents, such as daily habits in eating and physical activity, can affect their offspring. Epigenome-wide association studies (EWASs) use genome-wide assays, in order to demonstrate that cis- and trans-regulatory mechanisms shape patterns of popu- lation epigenomic variations in detail and as a whole. Different types of human cohort studies, ideally composed of mono-zygotic twins and best having a longitu- dinal design, are well suited to identify population epigenomic variations that are associated with human traits, such as disease risk. Aging may be the most important of these phenotypes, as it is everyone’s inevi- table result of life. The progressive decline in the function of cells, tissues and organs being associated with aging is affected by both genetic and epigenetic fac- tors, i.e. there are characteristic epigenome-wide changes during aging. Common hallmarks of aging are associated with specific chromatin patterns and chromatin modifiers are able to modulate both life- and healthspan. Thus, epigenomic signatures can serve as biomarkers of aging and may be druggable targets, in order to delay or reverse age-related disease. In this chapter, we will discuss the molecular basis of epigenetic memory in somatic cells and the potential for transgenerational inheritance via the germ line. We will present different types of human cohort studies that are suited for the inves- tigation of population epigenomics via EWAS and related assays. Finally, we will study the epigenomic basis of the aging process and the use of respective epigenetic signatures as biomarkers and drug targets for improving human healthspan.