Considering the importance of 5hmC in neurodevelopment, researchers have investigated the role of 5hmC in aging and neurodegenerative diseases. The two studies conducted on aging (from 6 weeks to 2 years) have found that global 5hmC levels increase in the hippocampus as aging occurs (Chen, Dzitoyeva, & Manev, 2012; Chouliaras et al.,

  • 2012) . Given this finding, more research is warranted to determine whether 5hmC also increases in other brain regions, as well as the specific loci with 5hmC enrichment across aging. Although there are not an expansive number of studies on neurodegeneration, several correlations have been found with 5hmC for both Huntington’s disease (HD) and Alzheimer’s disease (AD). In a mouse model of HD, a genome-wide decrease in 5hmC levels was found, correlating with decreases in gene expression (Wang et al.,
  • 2013) . The differentially hydroxymethylated regions contained genes involved in neuronal development and survival, which could have an important effect on the neurodegeneration seen in this disease (Wang et al., 2013). Additionally, studies in AD patients have seen a decrease in 5hmC in the hippocampus, and 5hmC levels were negatively correlated with amyloid plaque load, a common marker of AD pathogenesis (Chouliaras et al., 2013; Condliffe et al., 2014). However, another study looking at preclinical stages of AD saw an increase in 5hmC in hippocampal regions of the brain (Coppieters et al., 2014; Sun, Zang, Shu, & Li, 2014). Although preliminary, these studies point to a potential role of 5hmC in neurodegeneration through deregulation of gene expression. Additionally, 5hmC may act as a biomarker for diagnosing and determining the stage of the disease. Further research is required to understand the role 5hmC plays in neurodegeneration.
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