Molecular targets for the treatment of sarcopenia: a geroscience approach

Introduction Sarcopenia is increasingly recognized as a multisystem geroscience condition. The limited efficacy of first-generation anabolic therapies has challenged the paradigm that increasing muscle mass is sufficient to restore physical performance, highlighting the need for therapeutic strategies that address the biological complexity of muscle aging.Areas covered This review examines the evolution of molecular targets for sarcopenia, from anabolic pathways to emerging geroscience-based targets. We discuss mechanistic and clinical evidence supporting these approaches, emphasizing the distinction between molecular target engagement and functional efficacy, and examine how biological context, patient stratification, and multicomponent interventions influence therapeutic outcomes. The literature was identified through a comprehensive PubMed search, with emphasis on mechanistic studies, clinical trials, and recent advances in geroscience.Expert opinion The future of therapeutics against sarcopenia will likely depend less on identifying increasingly anabolic agents than on matching molecular targets to the dominant biological mechanisms limiting muscle function in individual patients. Biomarkers of target engagement, deep phenotyping, and mechanism-informed combination strategies integrating pharmacological, nutritional, and exercise interventions will be essential to improve patient stratification and translate molecular target modulation into meaningful functional benefit.