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. 2020 Oct:94:227-235.
doi: 10.1016/j.neurobiolaging.2020.06.003. Epub 2020 Jun 12.

The relationship between DNA methylation in neurotrophic genes and age as evidenced from three independent cohorts: differences by delirium status

Taku Saito  1 , Patricia R Braun  2 , Sophia Daniel  3 , Sydney S Jellison  3 , Mandy Hellman  3 , Eri Shinozaki  4 , Sangil Lee  5 , Hyunkeun R Cho  6 , Aihide Yoshino  7 , Hiroyuki Toda  7 , Gen Shinozaki  8
Affiliations

The relationship between DNA methylation in neurotrophic genes and age as evidenced from three independent cohorts: differences by delirium status

Taku Saito et al. Neurobiol Aging. 2020 Oct.

Abstract

We previously reported the association between DNA methylation (DNAm) of pro-inflammatory cytokine genes and age. In addition, neurotrophic factors are known to be associated with age and neurocognitive disorders. Therefore, we hypothesized that DNAm of neurotrophic genes change with age, especially in delirium patients. DNAm was analyzed using the Illumina HumanMethylation450 or 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. Both blood and brain samples showed that most of the DNAm of neurotrophic genes were positively correlated with age. Furthermore, DNAm of neurotrophic genes was more positively correlated with age in delirium cases than in non-delirium controls. These findings support our hypothesis that the neurotrophic genes may be epigenetically modulated with age, and this process may be contributing to the pathophysiology of delirium.

Keywords: Age; BDNF; Delirium; GDNF; Genome-wide DNA methylation; Neurotrophic factor.

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Conflict of interest statement

Disclosures

The other authors report no financial interests or potential conflicts of interest.

Figures

Figure 1
Figure 1
Correlation between age and DNA methylation level of the top two CpGs in the GTP cohort. Abbreviations: BDNF, Brain-derived neurotrophic factor; GDNF, glial cell-derived neurotrophic factor; GTP, Grady Trauma Project.
See this image and copyright information in PMC

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