Muscle epigenetics and long-term physical outcome after critical illness

Critically ill patients require vital organ support to avoid imminent death. Among other complications, they are at high risk of developing muscle weakness, associated with delayed weaning from mechanical ventilation, prolonged or incomplete rehabilitation and even death. Survival improved with advances in intensive care. However, a substantial proportion of the patients continue to experience adverse consequences long after hospital discharge. Persistent functional physical sequelae with muscle wasting and weakness may be most prominent and compromise quality of life. The molecular mechanisms underlying these long-term functional impairments currently remain to be unravelled. This project will address the hypothesis that the development of epigenetic changes in muscle may contribute to the long-term persistence of weakness in ICU survivors, which in turn may provide a new target for therapeutic intervention.