Control of skeletal muscle atrophy in response to disuse: clinical/preclinical contentions and fallacies of evidence

摘要: Muscle wasting resulting wholly or in part from disuse represents a serious medical complication that, when prolonged, can increase morbidity and mortality. Although much knowledge has been gained over the past half century, underlying etiology by which alters muscle proteostasis remains enigmatic. Multidisciplinary novel methodologies are needed to fill gaps overcome barriers improved patient care. The present review highlights seminal concepts symposium at Experimental Biology 2016. These proceedings focus on 1) role of insulin resistance mediating disuse-induced changes protein synthesis (MPS) breakdown (MPB), as well cross-talk between carbohydrate metabolism; 2) relative importance MPS/MPB involuntary loss humans animals; 3) interpretative limitations associated with "markers," e.g., MuRF1/MAFbx mRNA; finally, 4) how OMIC technologies be leveraged identify molecular pathways (e.g., ATF4, p53, p21) atrophy. This perspective deals primarily "simple atrophy" due unloading. Nonetheless, it is likely that pervasive contributor catabolic disease-related atrophy (i.e., sedentary behaviour disease burden). Key challenges identified stimulate discussion opportunities for translational research. Data animal human studies highlight both similarities differences. Integrated preclinical clinical research encouraged better understand metabolic underpinnings relevance,for approaches crucial clinically prevent reverse atrophy, thereby reestablishing homeostasis recovery.