DNA methylation change in neurotrophic genes with aging and delirium evidenced from three independent cohorts

Abstract

INTRODUCTION:We previously reported the association between DNA methylation (DNAm) of pro-inflammatory cytokine genes and aging. Neurotrophic factors are also known to be associated with aging and neurocognitive disorders. Thus, we hypothesized that DNAm of neurotrophic genes change with aging, especially in delirium patients. METHODS:DNAm were analyzed using HumanMethylationEPIC BeadChip Kit in 3 independent cohorts; blood from 383 Grady Trauma Project subjects, brain from 21 neurosurgery patients, and blood from 87 inpatients with and without delirium. RESULTS: Both blood and brain samples showed that most of the DNAm of neurotrophic genes were positively correlated with aging. Furthermore, DNAm of neurotrophic genes were positively correlated with aging in delirium cases than in non-delirium controls.DISCUSSION: These findings support our hypothesis that the neurotrophic genes may be epigenetically modulated with aging, and this process may be contributing to the pathophysiology of delirium.