Epigenetics of aging

The best-known phenomenon exemplifying epigenetic drift (the alteration of epigenetic patterns during aging) is the gradual decrease of global DNA methylation. Aging cells, different tissue types, as well as a variety of human diseases possess their own distinct DNA methylation profiles, although the functional impact of these is not always clear. DNA methylation appears to be a dynamic tool of transcriptional regulation, with an extra layer of complexity due to the recent discovery of the conversion of 5-methylcytosine into 5-hydroxymethylcytosine. This age-related DNA demethylation is associated with changes in histone modification patterns and, furthermore, we now know that ncRNAs have evolved in eukaryotes as epigenetic regulators of gene expression. In this review, we will discuss current knowledge on how all these epigenetic phenomena are implicated in human aging, and their links with external, internal and stochastic factors which can affect human age-related diseases onset.MFF and AFF are financially supported by Plan Nacional de I+D+I 2008-2011/2013-2016/FEDER (PI12/01080 to M.F.F.; and PI11/01728 to AF.F.), Fundación Ramón Areces (to M.F.F) and ISCIII-Subdirección General de Evaluación y Fomento de la Investigación (CP11/00131 to AFF). The IUOPA is supported by the Obra Social Cajastur, Spain.Peer Reviewe