Epigenetic modifications induced by critical illness with the muscle as paradigm

Survival of critically ill patients with a life-threatening condition has improved, but many survivors show longterm disabilities. One contributor to this is a specific form of muscle weakness, which frequently develops during acute illness. Our research team has extensively focused on many aspects of this problem, for which treatment options are still limited. Our data suggest that during acute illness damage is inadequately removed in the muscle, a cellular process resembling aging. This could contribute to long-term dysfunction. We thus hypothesize that critical illness leads to specific changes in the properties of the DNA within the cell -so-called epigenetic changes- closely mimicking those described in aging muscle, and causing an accelerated aging process that contributes to the ‘legacy’ of critical illness. We aim to demonstrate those epigenetic changes during critical illness, to examine how they are affected by metabolic factors, to study their long-term persistence and their relation with functional status. Understanding the underlying molecular events will provide new opportunities for treatment and reduce the burden of critical illness. In this project, we will use datasets and biopsy materials from 3 groups of intensive care patients. This project exemplifies a translational research approach starting from a clinical question, bringing clinical observations towards laboratory experiments to finally integrate these data and contribute to better patient care.

Keywords:Epigenetic, modifications, critical illness, muscle, paradigm

Disciplines:Anaesthesiology, Intensive care and emergency medicine