Unraveling Anabolic Resistance in Sarcopenia: A Narrative Synthesis of Age-Related Impairments in Muscle Protein Synthesis

OBJECTIVES Anabolic resistance, characterized by the diminished muscle protein synthesis (MPS) response to anabolic stimuli, represents the fundamental pathophysiological mechanism underlying age-related sarcopenia. This condition has a significant impact on clinical outcomes, including increased healthcare costs, disability, and mortality. To synthesize current clinical evidence on anabolic resistance mechanisms and evaluate evidence-based therapeutic interventions for its mitigation. METHODS This narrative synthesis was conducted by reviewing peer-reviewed clinical and translational studies published between January 2010 and March 2025. A structured search was performed in PubMed and Scopus using combinations of the keywords: “anabolic resistance”, “muscle protein synthesis”, “sarcopenia”, “resistance training”, “aging”, and “protein intake”. RESULTS Anabolic resistance manifests as an elevated protein threshold requirement (0.40 g/kg/day per meal vs. 0.24 g/kg/day in young adults) and reduced exercise-induced MPS stimulation. Physical inactivity amplifies this resistance through a feed-forward mechanism. Clinical evidence demonstrates that resistance training acts as the primary intervention to restore anabolic sensitivity, with effects lasting 24-48 hours post-exercise. Optimal protein distribution (1.2-1.6 g/kg/day divided into 0.4 g/kg/day per meal) is essential to overcome the elevated anabolic threshold. Creatine monohydrate supplementation provides additional benefits when combined with resistance training. CONCLUSIONS Anabolic resistance represents a modifiable clinical target. Evidence-based interventions combining resistance training with optimized protein nutrition can effectively restore anabolic sensitivity and prevent sarcopenia progression. Future research should focus on personalized approaches and long-term clinical outcomes.