title: Muscle wasting in disease: molecular mechanisms and promising therapies.
abstract: Atrophy occurs in specific muscles with inactivity (for example, during plaster cast immobilization) or denervation (for example, in patients with spinal cord injuries). Muscle wasting occurs systemically in older people (a condition known as sarcopenia); as a physiological response to fasting or malnutrition; and in many diseases, including chronic obstructive pulmonary disorder, cancer-associated cachexia, diabetes, renal failure, cardiac failure, Cushing syndrome, sepsis, burns and trauma. The rapid loss of muscle mass and strength primarily results from excessive protein breakdown, which is often accompanied by reduced protein synthesis. This loss of muscle function can lead to reduced quality of life, increased morbidity and mortality. Exercise is the only accepted approach to prevent or slow atrophy. However, several promising therapeutic agents are in development, and major advances in our understanding of the cellular mechanisms that regulate the protein balance in muscle include the identification of several cytokines, particularly myostatin, and a common transcriptional programme that promotes muscle wasting. Here, we discuss these new insights and the rationally designed therapies that are emerging to combat muscle wasting.
authors.affiliation: Faculty of Biology, Technion Institute of Technology, Haifa, 32000, Israel.
authors.forename: Shenhav
authors.initials: S
authors.lastname: Cohen
authors.affiliation: Cambridge Institute for Medical Research, Department of Medicine, University of Cambridge, Cambridge, CB2 0XY, UK.
authors.forename: James A
authors.initials: JA
authors.lastname: Nathan
authors.affiliation: Department of Cell Biology, 240 Longwood Ave., Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Alfred L
authors.initials: AL
authors.lastname: Goldberg
mesh_terms: D000818:Animals; D006801:Humans; D009133:Muscular Atrophy / Q000175:diagnosis* / Q000188:drug therapy* / Q000453:epidemiology; D009210:Myofibrils / Q000187:drug effects / Q000473:pathology; D055435:Myostatin / Q000494:pharmacology / Q000627:therapeutic use; D011788:Quality of Life; D018805:Sepsis / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D019282:Wasting Syndrome / Q000175:diagnosis / Q000188:drug therapy / Q000453:epidemiology
chemical_list: C525911:MSTN protein, human; D055435:Myostatin