Molecular Mechanisms of Age-Related Sarcopenia and Their Modulation by Exercise: A Narrative Review

Background: Sarcopenia is the progressive loss of muscle mass and strength with ageing and is a major cause of disability, reduced quality of life, and increased mortality in older adults. While exercise is widely recommended as a treatment, the molecular mechanisms by which it protects muscle remain incompletely understood. This review examines the key molecular pathways involved in age-related muscle wasting and evaluates how exercise therapy can modify these pathways. Aim: To provide a narrative review of the molecular mechanisms underlying sarcopenia in the elderly and to assess the potential of exercise therapy to reverse these mechanisms and improve clinical outcomes. We focus on three interrelated pathways: (1) myostatin signaling, (2) TNF-α inflammation, and (3) oxidative stress and endothelial dysfunction, with particular attention to their convergence on the IGF-I–Akt–mTOR pathway that regulates muscle protein synthesis. Methods: A systematic search of PubMed/MEDLINE was conducted using MeSH terms and free-text keywords related to sarcopenia, ageing, molecular mechanisms, and exercise. Studies examining molecular alterations in skeletal muscle and cardiac tissue in elderly individuals with sarcopenia were analyzed, with emphasis on the direct and indirect roles of exercise in restoring molecular balance. Results: Exercise-based interventions, particularly resistance and aerobic training, modulate the key molecular pathways involved in muscle wasting. Resistance training reduces myostatin expression and TNF-α levels, while aerobic exercise improves redox balance and endothelial function. These molecular changes are associated with increased muscle mass, strength, and functional capacity. Exercise also enhances signaling through the IGF-I–Akt–mTOR pathway, promoting muscle protein synthesis and inhibiting degradation. Nutritional supplementation (e.g., leucine, creatine, protein) may complement these effects by further activating anabolic signaling. Conclusion: Sarcopenia results from the convergence of multiple molecular pathways, including myostatin, TNF-α, and oxidative stress, all of which impair muscle protein synthesis and promote degradation. Exercise therapy counteracts these mechanisms at the molecular level, improving muscle mass, strength, and function. While exercise is currently the cornerstone of sarcopenia management, personalized prescriptions and combined interventions hold promise for optimizing outcomes in older adults.