The Trajectories of Neuromuscular Aging (TRAJECTOR-AGE Clinical Trial): Study Rationale and Methodological Protocol

Objectives: To examine the structural, metabolic, and functional trajectories of neuromuscular decline in aging and identify key mechanisms and early biomarkers to guide interventions preserving function and independence. Design: The TRAJECTOR-AGE project is a prospective, longitudinal cohort study conducted over 2 years across multiple centers in Italy. Setting and Participants: Community-dwelling, physically and cognitively healthy middle-aged (50–60 years) and older (> 70 years) adults are recruited. Individuals with significant comorbidities (e.g., diabetes, neurological disorders, severe heart failure) are excluded. Measurements: Participants undergo comprehensive clinical and physiological evaluations every 6 months, including assessments of geriatric status, body composition, cardiovascular function, and neuromuscular performance. Imaging includes periodic quadriceps ultrasound and annual multiparametric MRI to assess muscle volume and fat infiltration. Biological samples (blood, urine and Vastus lateralis muscle biopsy) are collected yearly to evaluate inflammatory, metabolic, and neuromuscular biomarkers. Expected Results: By integrating clinical, functional, and molecular data over time, the TRAJECTOR-AGE study aims to clarify the pathophysiological mechanisms underlying neuromuscular decline, capture inter-individual variability, and explore the influence of habitual physical activity on aging trajectories. Conclusions: This multidimensional approach may enable earlier identification of individuals at risk for functional decline and inform the development of targeted preventive or therapeutic interventions to promote independence and healthy aging.