Molecular Mechanisms of Skeletal Muscle AtrophyJakob Jespersen, master student of Human BiologyCopenhagen Muscle Research Centre Telephone: + 45 35 45 65 02 Description of ProjectSkeletal muscle constitutes the most abundant tissue of the human body, and is involved in different processes such as locomotion, breathing and metabolism. Loss of muscle mass (muscle atrophy) is a feature of physical inactivity, ageing and disease, and loss of muscle mass and stregth is associated with increased mortality. The contribution of skeletal muscle mass and strength to health is under-recognized, even though muscle atrophy because of physical inactivity and disease leads to premature physical frailty and decreased survival. Even a small degree of muscle atrophy (< 5 %) due to e.g. bed rest will worsen the prognosis and increase rehablitation demands and costs. The understanding of the molecular mechanisms of skeletal muscle atrophy has accelerated concurrently with the apperance and incorporation of molecular methods in muscle biology. One molecule that seems to play a very important role in muscle atrophy is the TGF-beta member myostatin. Myostatin is primarily expressed in striated skeletal and heart muscle, and is also present in fat cells, albeit to a lesser extent. What is more interesting is that repeated injections of myostatin-producing cells into mice induce severe muscle wasting (cachexia), and that myostatin is upregulated in patients with muscle loss. Furthermore, myostatin inhibition in mice, cattle and humans results in extraordinarily muscular phenotypes. Knowledge of the myostatin signal pathway including target cells and genes is limited. Additionally, there exist only a few studies regarding myostatin expression during human muscle hypertrophy and atrophy because of physical inactivity and disease, and most often they are limited to one or a few biopsies. Insight in the molecular mechanisms of skeletal muscle atrophy is of clinical relevans og could provide a basis for the development of both pharmacological and physical therapy against muscle wasting associated with physical inactivity, ageing and disease. Thus, the purpose of this master's thesis is to answer the following questions:
The supervisors of the project are Michael Kjaer, Institute of Sports Medicine, Peter Schjerling and Jesper L. Andersen, Copenhagen Muscle Research Centre. Presentation of Jakob JespersenJakob Jespersen, born 1978, holds a bachelor degree in Physical Education, Exercise & Sport Sciences from the Institute of Exercise & Sport Science, August Krogh Institute, University of Copenhagen. He will obtain his master degree in Human Biology from the Faculty of Health Sciences, University of Copenhagen in April 2006. He expects to continue as a PhD student with a project about the molecular mechanisms of skeletal muscle atrophy in critically ill intensive care patients. Publications
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