Sharma, Sayan, Hodges, Lynette D, Peppercorn, Katie et al. · International journal of molecular sciences · 2025 · DOI
This study looked at how exercise affects the chemical switches on our genes (epigenetics) in ME/CFS patients, particularly during post-exertional malaise (PEM)—the exhaustion that worsens after physical activity. Researchers took blood samples from five ME/CFS patients before, immediately after, and 24-48 hours after an exercise test, and found distinct patterns of genetic changes that were specific to ME/CFS patients and not seen in healthy controls. These changes affected genes related to immune function, inflammation, and blood vessel health, suggesting the body's response to exercise in ME/CFS is fundamentally different at the molecular level.
Understanding the epigenetic basis of PEM is crucial because it could reveal why ME/CFS patients deteriorate after exertion—a hallmark of the disease that distinguishes it from other conditions. Identifying molecular signatures specific to ME/CFS could eventually enable objective diagnostic tests and point toward therapeutic targets. This study provides the first detailed molecular timeline of genetic changes during PEM, potentially opening new avenues for precision medicine approaches.
This study does not prove that these epigenetic changes cause PEM or ME/CFS; it shows they occur together. With only five patients and two controls, results cannot be generalized to the broader ME/CFS population or determine whether changes are primary disease mechanisms or secondary responses to exertion. The study also cannot establish whether reversing these methylation changes would improve symptoms.
About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →
Contribute
Private, reviewed by a human. Not a public comment thread.