AUTHOR=Shinozaki Gen , Braun Patricia R. , Hing Benjamin W. Q. , Ratanatharathorn Andrew , Klisares Mason J. , Duncan Gabrielle N. , Jellison Sydney S. , Heinzman Jonathan T. , Nagahama Yasunori , Close Liesl , Sabbagh Sayeh , Dlouhy Brian J. , Howard Matthew A. , Kawasaki Hiroto , Cho Hyunkeun R.
TITLE=Epigenetics of Delirium and Aging: Potential Role of DNA Methylation Change on Cytokine Genes in Glia and Blood Along With Aging
JOURNAL=Frontiers in Aging Neuroscience
VOLUME=10
YEAR=2018
URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2018.00311
DOI=10.3389/fnagi.2018.00311
ISSN=1663-4365
ABSTRACT=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.