Identification and caracterization of mechanisms involved in skeletal muscle mass control and regeneration

Abstract

This project contains a series of proposals aiming to deepen the knowledge on cellular and molecular mechanisms that control skeletal muscle mass and regeneration. This knowledge is key to the future development of therapeutic strategies that can improve skeletal muscle viability, consequently increasing quality of life. Noteworthy, there are a number of key clinical conditions involving significant loss of skeletal muscle such as peripheral nerve injury, long term limb immobilisation, ageing and diseases with severe metabolic stress as AIDS, sepsis and cancer. In addition, maintanance of skeletal muscle mass is essencial for basic homeostasis, including daily motor activities (posture and movement), thermogenesis, energetic balance and immune response. Regenerative capacity is also a key adaptive feature of skeletal muscle, not only to repair large injuries, but also to repair micro injuries that occur by the ordinary mechanical demand. Indeed the slow and progressive loss of skeletal muscle mass in ageing is, among other factors, caused by lack of proper regeneration. Therefore, in certain conditions, skeletal muscle mass loss and regeneration are complementary and inter related processes. Subprojects 1-3 are directly related to understanding of underlying mechanisms. Another strategy will be to use an anti-atrophic agent (leucine) and another atrophic (Thyroid hormone) as models to identify possible target molecules/pathways (sub projects 4, 5, 6, 7 and 8). (AU)