Epigenetics of Delirium and Aging: Potential Role of DNA Methylation Change on Cytokine Genes in Glia and Blood Along With Aging

Frontiers in Aging Neuroscience

Hyunkeun R. Cho¹  Andrew Ratanatharathorn²  Brian J. Dlouhy³  Yasunori Nagahama³  Liesl Close³  Hiroto Kawasaki³  Matthew A. Howard³  Patricia R. Braun⁴  Jonathan T. Heinzman⁵  Gen Shinozaki⁵  Sayeh Sabbagh⁵  Sydney S. Jellison⁵  Gabrielle N. Duncan⁵  Benjamin W. Q. Hing⁵  Mason J. Klisares⁵ 

[1] Department of Biostatistics, College of Public Health, University of Iowa, Iowa City, IA, United States;Department of Epidemiology, School of Public Health, Columbia University Medical Center, Columbia University, New York, NY, United States;Department of Neurosurgery, University of Iowa, Carver College of Medicine, Iowa City, IA, United States;Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, United States;Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, IA, United States;

关键词: delirium;    epigenetics;    DNA methylation;    cytokine;    tNF-alpha;    aging;   

DOI  :  10.3389/fnagi.2018.00311

来源: DOAJ

【 摘 要 】

Background: Delirium in elderly patients is common and dangerous. Major risk factors include aging and exogenous insults, such as infection or surgery. In animal models, aging enhances pro-inflammatory cytokine release from microglia in response to exogenous insults. The epigenetic mechanism DNA methylation (DNAm) regulates gene expression and changes with age. Older individuals may have methylation changes that influence the increased cytokine upon insult, but the degree to which aging affects DNAm of cytokine genes is not fully understood.Methods: The relationship between DNAm and aging of pro-inflammatory cytokine genes (TNF-alpha, IL1-beta, IL-6) was investigated using methylation array data in two cohorts. Brain and blood samples were collected from a neurosurgery cohort (NSG) of 21 subjects who underwent brain resection. A second cohort, the Grady Trauma Project (GTP), included blood samples from 265 subjects.Results: In the NSG cohort, a significant negative correlation between age and DNAm in brain was found at a CpG in IL-6. With the GTP dataset, significant negative correlations between age and DNAm were seen at most of the CpGs in TNF-alpha. Also, TNF-Alpha expression increases with age. These GTP DNAm correlations were also nominally significant in NSG blood samples. In neuronal negative NSG brain tissue, a similar negative trend was observed.Conclusions: With aging, a decrease in DNAm of cytokines gene CpGs in glia and blood was seen. As this can affect their expression, additional research is needed to fully elucidate the role of DNAm in aging and how it may influence the pathogenesis of delirium.

【 授权许可】

Unknown