Identification, replication and characterization of epigenetic remodelling in the aging genome: A cross population analysis

摘要: Aging is a complex biological process regulated by multiple cellular pathways and molecular mechanisms including epigenetics. Using genome-wide DNA methylation data measured in large collection of Scottish old individuals, we performed discovery association analysis to identify age-methylated CpGs replicated them two independent Danish cohorts. The double-replicated were characterized distribution over gene regions location relation CpG islands. further involvement study their functional implications aging. We identified 67,604 age-associated sites reaching significance FWER <0.05, 86% demethylated with increasing age. Double-replication resulted 5,168 (39% 61% age-demethylated) which high concentration at 1stExon TSS200 dominant pattern age-demethylated other regions, overwhelming age-related islands demethylation shore/shelf open sea. differential patterns for methylated both relate reduced activity during Pathway showed that age-dependent methylations especially involved signalling activities while demethylations particularly linked functions the extracellular matrix, all implicated aging disease risk.