tailieunhanh - Sarcopenia – Age-Related Muscle Wasting and Weakness - Part 2 ( end)

Tham khảo sách 'sarcopenia – age-related muscle wasting and weakness - part 2 ( end)', y tế - sức khoẻ, y học thường thức phục vụ nhu cầu học tập, nghiên cứu và làm việc hiệu quả | Role of Myostatin in Skeletal Muscle Growth and Development Implications for Sarcopenia Craig McFarlane Mridula Sharma and Ravi Kambadur Abstract Myostatin is a secreted growth and differentiating factor that belongs to TGF-b super-family. Myostatin is expressed in skeletal muscle predominantly. Low levels of myostatin expression are seen in heart adipose tissue and mammary gland. Naturally occurring mutations in bovine ovine canine and human myostatin gene or inactivation of the murine myostatin gene lead to an increase in muscle mass due to hyperplasia. Molecularly myostatin has been shown to regulate muscle growth not only by controlling myoblast proliferation and differentiation during fetal myogenesis but also by regulating satellite cell activation and self-renewal postnatally. Consistent with the molecular genetic studies injection of several myostatin blockers including Follistatin myostatin antibodies and the Prodomain of myostatin have all been independently shown to increase muscle regeneration and growth in muscular dystrophy mouse models of muscle wasting. Furthermore prolonged absence of myostatin in mice has also been shown to reduce sarcopenic muscle loss due to efficient satellite cell activation and regeneration of skeletal muscle in aged mice. Similarly treatment of aged mice with Mstn-ant 1 also increased satellite cell activation and enhanced the efficiency of muscles to regenerate. Given that antagonism of myostatin leads to significant increase in postnatal muscle growth we propose that myostatin antagonists have tremendous therapeutic value in alleviating sarcopenic muscle loss. Keywords Myostatin GDF-8 Skeletal muscle Smad Wnt Proliferation Differentiation Satellite cells Muscle wasting Atrophy Cachexia Sarcopenia R. Kambadur School of Biological Sciences Nanyang Technological University 60 Nanyang Drive Singapore e-mail Kravi@ C. McFarlane and R. Kambadur Singapore Institute for Clinical Sciences Singapore M. Sharma Department of