Ziel
Muscle loss occurs in many diseases including cancer, AIDS, diabetes, renal or cardiac failure and sepsis. The wasting of muscle mass is characterized by the activation of an atrophy program that coordinates the ubiquitin-proteasome and autophagy-lysosome systems. The simultaneous activation of these systems allows the breakdown of contractile proteins and the removal of organelles. Ageing sarcopenia and frailty are also characterised by progressive muscle loss. However, the mechanisms that are at the base of this weakness are obscure. Sarcopenia results in a progressive loss of mobility that decreases the quality of life and has major economic and social consequences. In fact the age-dependent muscle atrophy favour traumatic events, accident, fracture or illness which lead to aged person to become hospitalised and bed-ridden or housebound, thus -having a high mortality in the year following their accident. The signalling pathways, which regulate loss of proteins and organelles in muscle fibers, are just at the beginning to be understood. We have recently found that autophagy-lysosome system is critical to maintain muscle mass and that its alteration leads to muscle atrophy, weakness and to several features that are present in ageing sarcopenia. Thus, dissecting the regulation of autophagy system in skeletal muscle and its role in muscle homeostasis is crucial for developing new therapeutic tools to counteract sarcopenia. This project is an effort in this direction. We aim: i) to identify molecular mechanisms and pathways which are responsible for autophagy regulation in skeletal muscle and which may be targeted to combat age related muscle weakness, (ii) to dissect the cross-talk between muscle and nerve, (iii) to determine the cross-talk between autophagy-lysosome and ubiquitin-proteasome, iv) to translate the findings obtained in animal models to human skeletal muscles.
Wissenschaftliches Gebiet
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- medical and health sciencesclinical medicineendocrinologydiabetes
- medical and health scienceshealth sciencesinfectious diseasesRNA virusesHIV
- medical and health sciencesclinical medicineoncology
- medical and health sciencesbasic medicinephysiologyhomeostasis
Aufforderung zur Vorschlagseinreichung
ERC-2011-StG_20101109
Andere Projekte für diesen Aufruf anzeigen
Finanzierungsplan
ERC-SG - ERC Starting GrantGastgebende Einrichtung
35129 Padova
Italien