Structural MR correlates of epigenetic age acceleration

Late-life neuropsychiatric disorders are among the leading causes of morbidity and mortality, and methods to predict such risk are seeked. One new peripheral biomarker of aging-related changes is the methylation status of DNA Cytosine-phosphate-Guanosine sites (CpGs). A promising epigenome-wide biomarker is a recently reported predictor comprised of 353 age-susceptible CpGs (DNA methylation age predictor or “epigenetic clock”) that showed strong correlations with chronological age across multiple tissues, including several brain regions, in humans (Horvath 2013). The difference between DNA methylation-predicted age and chronological age, denoted as epigenetic age acceleration, has been proposed as a measure of accelerated biological aging (Horvath 2013) and was shown to predict allcause mortality and worse physical and cognitive performance. Furthermore, Zannas et al. found and replicated that epigenetic age acceleration is associated with cumulative exposure to lifetime stressors and depressive symptomatology. At the brain level, recurrent MDD – a condition similarly associated with chronic psychosocial stress – is associated with hippocampal structural deficits and an increased risk to develop dementia. In this epigenetic/MRI study on N = 627 (MDD, controls) we aim at linking an whole genome epigenetic marker of aging and brain structure, focussing on hippocampal structure, and hypothesizing that epigenetic age acceleration is associated with loss of hippocampal integrity.