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DNA methylation is an example of an epigenetic modification that can influence the expression of genes without changing the DNA sequence. As people age, changes in DNA methylation accumulate and the rate of these changes compared to chronological age (known as epigenetic age) can be used to predict health outcomes, such as cancer. Long-term, or ‘chronic’, inflammation is associated with a broad range of non-communicable diseases, including cardiovascular disease and cancer. In this paper, the research team investigated the relationship between inflammation and changes in DNA methylation.
The researchers focused on a type of immune cell called a monocyte, which is known to be important in the inflammatory response. They examined DNA methylation levels in monocytes, which were taken from 192 healthy adults, with and without exposure of the cells to inflammatory stimuli and mapped the changes caused by the inflammation. This revealed large-scale changes in DNA methylation in the immune cells. These changes were linked to genes that are often mutated in cancer, suggesting that changes in DNA methylation could form a link between inflammation and genetic mutations.
When mapping the DNA methylation, the research team observed that treatment with lipopolysaccharide led to the most significant changes. Additionally, they found that just 24 hours of stimulation with lipopolysaccharide increased the epigenetic age of the cells by approximately 6 months. This suggested a link between inflammation and age acceleration. Furthermore, they also observed that many of the changes in DNA methylation were controlled by genetic differences between individuals, including in genes associated with autoimmune disease.
First author Dr James Gilchrist, an NIHR Academic Clinical Lecturer in the Fairfax Group, said:
“Our work suggests a model whereby our lifetime burden of infection and inflammation in tandem with genetic variation adds to cumulative changes to our DNA methylation, and that these changes could contribute to the risk of cancer and other health outcomes in the long-term.”
Read the full paper here: https://doi.org/10.1016/j.xgen.2024.100541