DNA methylation patterns in aging

Brain aging is a relative process characterized by a progressive decline in homeostasis, stress responses and cognitive functions. At cellular level, it is associated with molecular markers such as telomere length and DNA methylation clocks, which are believed to capture different aspects of relative aging. Additionally, changes in histone modifications and gene transcription also occur. However, a complete description of epigenetic changes in middle- to old-aged brains is still missing. Here, we provide a comprehensive characterization of age-associated DNA methylation changes in the healthy brain between 30 and 90 years of age. Human frontal cortex samples were obtained from the Spanish National Network of Biobanks, NeuN+ cells characterized by enzymatic methyl-seq (EM-seq) and RNA sequencing, and resulting data analyzed using an in-house developed R pipeline. Our results provide an unprecedented resolution of DNA methylation changes through age and remark potential interactions with other epigenetic layers that impact on specific pathways and genes. These findings may pave the way for the development of new therapies to counteract the undesired effects of brain aging.