<p>Sarcopenia is a prevalent and debilitating skeletal muscle disorder in the aging population, characterized by progressive loss of muscle mass, strength, and function. Despite its significant impact on mobility, independence, and healthcare systems worldwide, effective pharmacological treatments remain limited. Recent advances in the understanding of sarcopenia pathophysiology have identified myostatin—a potent negative regulator of muscle growth—as a promising therapeutic target. Myostatin inhibitors—comprising direct agents such as monoclonal antibodies and small molecules, as well as indirect modulators including follistatin-based strategies and other pathway regulators—have demonstrated encouraging results in preclinical and early clinical studies by increasing muscle mass and improving muscle function. This comprehensive review summarizes current knowledge of myostatin’s molecular mechanisms in muscle homeostasis, evaluates the efficacy and safety of various myostatin-targeted therapies in sarcopenia, and discusses the translational challenges and future directions for clinical application. The integration of myostatin inhibition into therapeutic regimens offers the potential to address a critical unmet need in sarcopenia management and improve the quality of life for elderly individuals.</p>

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Myostatin inhibitors in sarcopenia treatment: A comprehensive review of mechanisms, efficacy and future directions

  • Sahar Ahmad Samali,
  • Seyede Fatemeh Hosseini,
  • Yaser Mohammadi,
  • Farzad Sadri,
  • Zohreh Rezaei

摘要

Sarcopenia is a prevalent and debilitating skeletal muscle disorder in the aging population, characterized by progressive loss of muscle mass, strength, and function. Despite its significant impact on mobility, independence, and healthcare systems worldwide, effective pharmacological treatments remain limited. Recent advances in the understanding of sarcopenia pathophysiology have identified myostatin—a potent negative regulator of muscle growth—as a promising therapeutic target. Myostatin inhibitors—comprising direct agents such as monoclonal antibodies and small molecules, as well as indirect modulators including follistatin-based strategies and other pathway regulators—have demonstrated encouraging results in preclinical and early clinical studies by increasing muscle mass and improving muscle function. This comprehensive review summarizes current knowledge of myostatin’s molecular mechanisms in muscle homeostasis, evaluates the efficacy and safety of various myostatin-targeted therapies in sarcopenia, and discusses the translational challenges and future directions for clinical application. The integration of myostatin inhibition into therapeutic regimens offers the potential to address a critical unmet need in sarcopenia management and improve the quality of life for elderly individuals.