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Methylation is a modification in which DNA is given a ‘tag’ that can change the way a gene is expressed. Genetics and environmental factors can cause DNA methylation patterns to change over time, and researchers can measure the accumulation of such changes in order to estimate how quickly a person is ageing. This method, known as a methylation clock, is designed to predict age, but whether DNA methylation can also be used to predict risk of death is not clear.
In the largest study of its kind to date, researchers explored this possibility. They analysed results from multiple studies including 12 300 participants in total, and were able to identify nine specific methylation sites in blood DNA that predict mortality, independently of other risk factors. Of the nine sites identified, six were associated with reduced mortality when methylated while the remaining three increased mortality. This held true regardless of an individual’s chronological age, lifestyle habits or health conditions.
The researchers were also able to correlate the methylation state of certain sites to specific age-related diseases.
Of the nine sites, three were associated with lower incidence of heart disease risk and two with smoking and inflammation in prior CHARGE analyses. Methylation of [three sites] was associated with decreased expression of nearby genes linked to immune responses and cardiometabolic diseases.
It therefore seems that specific methylation sites can predict mortality, serving as markers for changes in gene expression that influence risk of chronic age-related diseases. This could prove useful clinically, allowing us to better predict an individual’s mortality risk and respond with appropriate preventative measures.
Blood DNA methylation sites predict death risk in a longitudinal study of 12, 300 individuals: https://doi.org/10.18632/aging.103408
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