MYOSTATIN (GDF-8) AS A CENTRAL REGULATOR OF SKELETAL MUSCLE GROWTH AND METABOLISM: MECHANISMS, CLINICAL EVIDENCE AND THERAPEUTIC POTENTIAL

ABSTRACT Myostatin (GDF-8) is a member of the transforming growth factor-β family and a key negative regulator of skeletal muscle growth. It inhibits satellite-cell activity and muscle protein synthesis and also modulates whole-body metabolism, adipose-tissue function, bone remodelling, and endocrine signalling. Excessive myostatin activity has been linked to sarcopenia, muscular dystrophies, cachexia, obesity, insulin resistance, and cardiometabolic disorders. These broad actions make selective myostatin inhibition an attractive therapeutic strategy in conditions characterised by muscle wasting and impaired metabolic health. The aim of this narrative review is to summarise current knowledge on myostatin molecular structure, activation, and signalling pathways; to describe its roles in skeletal muscle, metabolism, and other organ systems; and to analyse preclinical and clinical evidence supporting pharmacological, gene-based, nutritional, and exercise-based approaches to myostatin inhibition. A structured search of major scientific databases was performed to identify experimental, translational, and clinical studies on myostatin biology and therapeutic targeting. Available evidence indicates that blocking myostatin can increase lean mass, improve insulin sensitivity, and reduce adiposity. However, gains in muscle strength and function are variable, emphasising the importance of combining pharmacological inhibition with resistance training and optimised nutritional support. New agents that selectively target pro-myostatin or activin receptors appear safer and more effective than earlier broad-spectrum inhibitors. In conclusion, myostatin is a central regulator of muscle and metabolic homeostasis and a promising therapeutic target. Integrated strategies combining selective myostatin inhibition with exercise, nutrition, and personalised biomarker profiling are likely to provide the greatest clinical benefits.