Abstract
There is a growing need for biomarkers which predict age-onset pathology. Although this is challenging, the methylome offers significant potential. Cancer is associated with the hypermethylation of many gene promoters, among which are developmental genes. Evolutionary theory suggests developmental genes arbitrate early-late life trade-offs, causing epimutations that increase disease vulnerability. Such genes could predict age-related disease. The aim of this work was to optimise an electrochemical procedure for the future investigation of a broad range of ageing-related pathologies. An electrochemical approach, which adopted three analytical techniques, was used to investigate DNA methylation in the engrailed-1 (EN1) gene promoter. Using synthetic single-stranded DNA, one technique was able to detect DNA at concentrations as low as 10 nM, with methylation status distinguishable at concentrations >25 nM. A negative correlation could be observed between % methylation of a heterogeneous solution and the key electrochemical parameter, charge transfer resistance (Rct; r = −0.982, P<0.01). The technique was applied to the breast cancer cell line Michigan Cancer Foundation-7 (MCF-7), where a similar correlation was observed (r = −0.965, P<0.01). These results suggest electrochemistry can effectively measure DNA methylation at low concentrations of DNA. This has implications for the future detection of age-related disease.
Highlights
Ageing is a complex biological phenomenon which is characterised by a decline in physical function [1]
We have demonstrated that this simple electrochemical procedure can detect DNA methylation in both homogeneous and heterogeneous samples of synthetic single stranded DNA (ssDNA) and breast cancer cell line Michigan Cancer Foundation-7 (MCF-7) DNA
Electrochemical techniques are a useful tool for detecting changes in DNA methylation patterns, which can be associated with disease such as cancer
Summary
Ageing is a complex biological phenomenon which is characterised by a decline in physical function [1] This physical deterioration results in an increased risk of a multitude of age-related diseases, such as cardiovascular disease (CVD), Alzheimer’s disease (AD) and cancer [2]. These diseases place a significant burden on the wellbeing of older people. From a global perspective, 60% of all cancer cases and 70% of cancer-related deaths occurs in older people (those ≥65 years) [4] Based on this evidence it is cogent that appropriate biomedical tools are developed to help diagnose and predict age-associated diseases so the healthspan of older people can be extended. Global hypomethylation is observed in conjunction with site-specific hypermethylation at the promoter region of a variety of genes, which have been ubiquitously associated
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