Unraveling the Role of Epigenetics in Aging and Chronic Disease.

Abstract

Healthy aging is defined as aging in the absence of chronic diseases that limit physical function and mobility. With the increasingly high prevalence of chronic diseases and their risk factors in the United States, it is important to better understand the contributors and predictors of health and longevity. Molecular markers of the epigenome provide one novel set of biomarkers to investigate the intersection of the effects of genetic variation and environmental variation in the initiation and progression of chronic disease. This dissertation focuses on (1) investigating associations between 26,428 DNA methylation markers and chronological age, (2) elucidating the environmental and genetic components of the variation of 26,428 DNA methylation markers, and, finally, (3) predicting aging with DNA methylation markers sites in an African-American population of sibships from the Jackson, MS field center of the Genetic Epidemiology Network of Arteriopathy (GENOA) study. We found that 27% of the genome-wide DNA methylation sites are significantly associated with age. The majority of DNA methylation sites (88%) have significant heritabilities, and there is evidence of an age-related genetic component to this heritability. Finally, when predicting aging, inflammatory biomarkers and DNA methylation markers, together, were found to explain 14% of the variation in aging. This dissertation illustrates that DNA methylation patterns measured in epidemiological studies may be able to provide new insights into the molecular processes underlying aging and chronic disease development.