The loss of skeletal muscle mass is strongly related to mortality and morbidity in hospitalized patients. In these patients, physical inactivity together with systemic inflammation are associated with mitochondrial dysfunction, insulin resistance and anabolic resistance. However, how these factors interact on a cellular and molecular level is currently unknown. In this translational PhD project, funded by AMS, we aim to study this using a variety of models and novel techniques.

Hospitalized patients mainly suffer from physical inactivity in combination with (low-grade) systemic inflammation. Both physical inactivity and systemic inflammation are often associated with muscle atrophy and exercise intolerance, even months after discharge. It is therefore likely that the effects of physical inactivity are exacerbated by low-grade inflammation.

In this PhD project, funded by the Amsterdam Movement Sciences, we aim to study the metabolic consequences of physical inactivity and systemic inflammation using a variety of models and techniques.

One aspect of this work focuses on cellular inflammation and mitochondrial function in skeletal muscle cells. We highlight the role of mitochondrial dysfunction in inflammation-induced muscle atrophy using cultured cells, using state-of-the-art microscopic imaging, various molecular techniques and functional assays.

In other parts of this translational project we will systematically study the time course of metabolic adaptations in skeletal muscle during inactivity in combination with systemic inflammation in preclinical models, and in human hospitalized patients.

Together with ESA and NASA, we are involved in large human bedrest studies, and even plan to test zero-gravity-induced muscle adaptations in astronauts. Nutritional and exercise interventions are planned in rodent studies and in hospital patients.

Together, these studies will provide novel fundamental and translational information on the molecular mechanisms of inactivity-induced muscle dysfunction, and provide new avenues for immediately applicable nutritional intervention therapies for bedridden patients.
PhD candidate M. Eggelbusch at work in the lab
PhD candidate M. Eggelbusch at work in the lab

Researchers involved in this project

  • Dr. Michael Tieland;