The role of DNA methylation in ageing and cancer

Proc Nutr Soc. 2018 Nov;77(4):412-422. doi: 10.1017/S0029665118000150. Epub 2018 Apr 30.

Abstract

The aim of the present review paper is to survey the literature related to DNA methylation, and its association with cancer and ageing. The review will outline the key factors, including diet, which modulate DNA methylation. Our rationale for conducting this review is that ageing and diseases, including cancer, are often accompanied by aberrant DNA methylation, a key epigenetic process, which is crucial to the regulation of gene expression. Significantly, it has been observed that with age and certain disease states, DNA methylation status can become disrupted. For instance, a broad array of cancers are associated with promoter-specific hypermethylation and concomitant gene silencing. This review highlights that hypermethylation, and gene silencing, of the EN1 gene promoter, a crucial homeobox gene, has been detected in various forms of cancer. This has led to this region being proposed as a potential biomarker for diseases such as cancer. We conclude the review by describing a recently developed novel electrochemical method that can be used to quantify the level of methylation within the EN1 promoter and emphasise the growing trend in the use of electrochemical techniques for the detection of aberrant DNA methylation.

Keywords: CGI CpG islands; CH3 methyl; CR caloric restriction; DNMT DNA methyltransferases; MDS myelodysplastic syndromes; TET ten–eleven translocation; Ageing; Cancer; DNA methylation; Electrochemistry.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aging / genetics
  • Aging / metabolism*
  • DNA / metabolism
  • DNA Methylation*
  • Diet*
  • Epigenesis, Genetic*
  • Gene Silencing
  • Genes, Homeobox*
  • Homeodomain Proteins / genetics
  • Humans
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • Promoter Regions, Genetic*

Substances

  • EN1 protein, human
  • Homeodomain Proteins
  • DNA