Ageing and epigenetics: linking neurodevelopmental and neurodegenerative disorders

Abstract

Epigenetics has classically been recognized as crucial to neurodevelopment and neurodevelopmental disorders. More recently its role in ageing processes, including neurodegenerative disorders has emerged, although far more research is required in this area, particularly in humans. Epigenetic processes that regulate gene expression comprise strata of DNA modification (e.g. methylation), histone modification (e.g. histone acetylation), and mRNA translation (e.g. by microRNAs). These strata are progressively more fluid whereby changes in DNA methylation may persist for many years whilst expression of microRNAs fluctuates over short periods. There is considerable ‘cross-talk’ between these epigenetic strata. Epigenetic mechanisms are open to parental imprinting and thus they are candidates for linking diseases, not just over the life course, but also intergenerationally. There is a genetic overlap between intellectual disability and cognitive ageing. Epigenetic pathways may strengthen the links between neurodevelopmental disorders and neurodegenerative diseases. What this paper adds: DNA methylation has relevance to both neurological development and neurodegeneration. Links between epigenetics, genotype and phenotype are emerging.