PURPOSE OF REVIEW: To describe the most relevant recent observations concerning the molecular mechanisms behind myostatin-induced muscle wasting. RECENT FINDINGS: The main theme of this review is to summarize the biology and function of myostatin. Myostatin is a secreted growth factor that negatively regulates muscle growth. While inactivation of myostatin leads to muscle growth in vivo, excess levels of myostatin induces cachectic-like muscle wasting. Molecular analyses reveal that excess levels of myostatin induce Atrogin-1 expression by reducing Akt phosphorylation and thereby increasing FoxO1 activity. Recent findings have further speculated that myostatin may also play a role in cardiac cachexia. SUMMARY: As myostatin is a potent inducer of muscle wasting, antagonists to myostatin have been speculated to have great therapeutic value in alleviating muscle wasting. Indeed, myostatin peptide antagonists and antibodies have shown great promise in containing muscle loss in animal models of muscle wasting. Given the beneficial effects of myostatin antagonists in animal models, clinical trials are underway with myostatin antibodies, peptibodies and soluble receptor. Therefore, this review article on the role of myostatin in muscle wasting is highly relevant to current themes in muscle biology.
PURPOSE OF REVIEW: To describe the most relevant recent observations concerning the molecular mechanisms behind myostatin-induced muscle wasting. RECENT FINDINGS: The main theme of this review is to summarize the biology and function of myostatin. Myostatin is a secreted growth factor that negatively regulates muscle growth. While inactivation of myostatin leads to muscle growth in vivo, excess levels of myostatin induces cachectic-like muscle wasting. Molecular analyses reveal that excess levels of myostatin induce Atrogin-1 expression by reducing Akt phosphorylation and thereby increasing FoxO1 activity. Recent findings have further speculated that myostatin may also play a role in cardiac cachexia. SUMMARY: As myostatin is a potent inducer of muscle wasting, antagonists to myostatin have been speculated to have great therapeutic value in alleviating muscle wasting. Indeed, myostatin peptide antagonists and antibodies have shown great promise in containing muscle loss in animal models of muscle wasting. Given the beneficial effects of myostatin antagonists in animal models, clinical trials are underway with myostatin antibodies, peptibodies and soluble receptor. Therefore, this review article on the role of myostatin in muscle wasting is highly relevant to current themes in muscle biology.