Influence of Epigenetic Modifications on Post-Exertional Malaise in People with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex and disabling condition characterized by chronic fatigue, widespread pain and hyperalgesia, and other cognitive symptoms such as difficulties to concentrate and memory impairment. According to recent diagnostic criteria, the most characteristic and disabling symptom of the disease is arguably the presence of post-exertional malaise. Its pathophysiology is poorly understood, and unravelling the exact underlying ME/CFS biology is urgently needed for developing new and more effective treatments. In recent years, an increasing amount of research has focused on understanding the pathophysiology of ME/CFS and post-exertional malaise. Research has highlighted the role of oxidative stress, immune system and neuroimmune cells activation, and central nervous system alterations – including increased sensitivity of the central nervous system to sensory input (i.e. central sensitization). Several factors potentially involved in the mechanisms underlying these processes, such as brain derived neurotrophic factor, Catechol-O-methyltransferase, histone de-acetylases and serotonin, might be able to explain patients’ symptoms and post-exertional malaise, especially because some of these factors are altered in response to exercise. Epigenetic mechanisms, including DNA methylation and histone acetylation, have been found to be involved in the regulation of factors that are potentially key players in ME/CFS and more specifically post exertional malaise. Therefore, epigenetics holds promise to unravel mechanisms underlying post-exertional malaise in ME/CFS. Only a few studies explored DNA methylation in patients with ME/CFS. Initial results showing altered methylation in genes related to immune responses, kinase activity, and neural plasticity are promising but come from cross-sectional studies. To the best of our knowledge no study assessed the effect of exercise on epigenetic changes, nor the relation between DNA methylation and post-exertional malaise in patients with ME/CFS. This is an important research gap. Understanding post-exertional malaise in relation to epigenetic processes such as DNA methylation would likely provide new targetable core mechanisms for developing new strategies and treatments. Therefore, this doctoral trajectory will be focused on investigating the role of epigenetic mechanisms in post-exertional malaise in ME/CFS.