Therapeutic advances in sarcopenia management: From traditional interventions to personalized medicine

Sarcopenia, a progressive decline in skeletal muscle mass and function, has emerged as a critical geriatric syndrome affecting 10-40% of older adults, contributing to increased disability and mortality. This comprehensive review evaluates evidence-based strategies for sarcopenia management, from established interventions to emerging personalized approaches. Pathophysiological insights reveal multifactorial mechanisms involving anabolic resistance, chronic inflammation (elevated IL-6, TNF-α), hormonal imbalances (e.g., testosterone/IGF-1 decline), neuromuscular junction dysfunction, mitochondrial impairment, and novel mediators like GDF-15, which drive proteolysis and appetite suppression. Non-pharmacological interventions demonstrate robust efficacy: combined resistance-aerobic exercise regimens (2-3 sessions/week) improve muscle strength by 20-35%, while optimized protein intake (1.0-1.5 g/kg/day) with leucine or vitamin D supplementation enhances muscle synthesis and functional capacity. Pharmacological trials highlight selective androgen receptor modulators (SARMs) and myostatin inhibitors (e.g., bimagrumab) increasing lean mass by 3-5% in phase II studies, with GDF-15-neutralizing antibodies emerging as promising anti-catabolic agents. Advanced therapies, including stem cell transplantation and AAV-mediated gene editing targeting myostatin/IGF-1 pathways, show preclinical regenerative potential. However, clinical translation requires validation through large-scale trials. Personalized strategies integrating biomarkers, comorbidities, and digital monitoring tools optimize intervention efficacy, particularly in complex populations like diabetic or cachectic patients. This synthesis underscores the paradigm shift toward precision medicine but identifies critical knowledge gaps, including long-term safety of biologics and cost-effectiveness of regenerative approaches. Future research should prioritize multimodal therapies, validated biomarkers, and AI-driven algorithms to individualize sarcopenia management in aging populations.