Journal
NATURE REVIEWS DRUG DISCOVERY
Volume 14, Issue 1, Pages 58-74Publisher
NATURE PORTFOLIO
DOI: 10.1038/nrd4467
Keywords
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Funding
- US National Institutes of Health [ARO55255]
- Muscular Dystrophy Association
- Wellcome Trust
- International Sephardic Education Foundation (ISEF)
- MRC [G0802822] Funding Source: UKRI
- Medical Research Council [G0802822] Funding Source: researchfish
- Wellcome Trust [102770/Z/13/Z] Funding Source: researchfish
- Wellcome Trust [102770/Z/13/Z] Funding Source: Wellcome Trust
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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.
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