Myostatin and Sarcopenia: Opportunities and Challenges - A Mini-Review

Thomas A. White, Nathan K. LeBrasseur
2014 Gerontology  
quences for skeletal muscle performance, physical function and metabolism in older persons, and thus, poses a major medical and economic threat to society. The biological mechanisms that underlie sarcopenia remain incompletely understood, but are influenced by multiple factors including age-associated changes in hormones, sex steroids, physical inactivity, and comorbid conditions such as heart failure, cancer, and diabetes. As a result, untangling the causal molecular pathways in attempt to
more » ... tify therapeutic targets to prevent, delay or reverse sarcopenia has proven challenging. In recent years there has been significant interest in growth and differentiation factor-8 (GDF-8), or myostatin, which functions as a powerful negative regulator of muscle growth [1] . The purpose of this review is to highlight the opportunities for myostatin inhibition as a strategy to counter sarcopenia, as well as discuss the challenges that have confronted its progression. Myostatin Signaling in Skeletal Muscle Myostatin is a highly conserved member of the transforming growth factor-β superfamily. It is abundant in skeletal muscle, but also expressed to a lesser extent in adipose tissue and cardiac muscle [1, 2] . Myostatin signals through the activin type IIB receptor (ActRIIB), which is expressed ubiquitously and forms a heterodimer with activin-like kinase 4 (ALK4) or ALK5. The intracel- Abstract The progressive loss of skeletal muscle mass, strength and/ or function with advancing age, termed sarcopenia , poses a major threat to independence and quality of life. Therefore, there is significant merit in better understanding the biology of sarcopenia and developing therapeutic interventions to prevent, slow or reverse its progression. Since the discovery of myostatin, a potent negative regulator of growth that is highly enriched in skeletal muscle, there has been great interest in it as a potential mediator of sarcopenia as well as a therapeutic target. The complex biology of myostatin, the promise of myostatin inhibition as an effective means to counter sarcopenia, and the challenges facing its clinical translation are reviewed herein.
doi:10.1159/000356740 pmid:24457615 fatcat:6g3nofvai5dxbiyzfz2uvyrj2i