Role of myostatin in skeletal muscle growth and development: Implications for sarcopenia

Abstract

Myostatin is a secreted growth and differentiating factor that belongs to TGF-β 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.