Regulation of muscle mass

Skeletal muscle is essential to life as it provides the mechanical power for locomotion. Loss of muscle mass – atrophy - occurs during inactivity (for instance during plaster cast or immobilization) or denervation (in patients with spinal cord injury or in neurodegenerative disease like amyotrophic lateral sclerosis).  In our aging population, muscle atrophy due to long-term inactivity is a major cause of morbidity and mortality. Moreover, it is a critical component of many diseases such as chronic obstructive pulmonary disorder, diabetes, cardiac failure and sepsis. In this respect, recent studies have also shown that muscle atrophy in cancer patients (termed cancer cachexia) is likely to be the major causes of death in those patients. Thus, the development of treatments to prevent muscle atrophy is of major importance for many clinical conditions.

The loss of muscle mass following denervation or inactivity primarily results from excessive protein breakdown, often accompanied by reduced protein synthesis. The transcriptional program controlling muscle atrophy seems to be quite similar amongst various inactivation/denervation conditions, as numerous studies have shown the activation of a specific set of genes, the so-called atrogenes, during muscle wasting. In particular, there is an increase in the expression of two muscle-specific ubiquitin ligases, atrogin-1/MAFbx and MuRF-1, whose induction occurs before the onset of muscle weight loss and which are necessary for rapid atrophy since they catalyze the degradation of the proteins comprising the muscle in a specific order. Nevertheless, the upstream metabolic signals that result into active protein breakdown are poorly described.

Using in vivo and in vitro models, the Laboratory for Exercise and Health will try to elucidate the metabolic regulation of muscle mass.