Nutritional Strategies for Musculoskeletal Aging: Targeting Mitochondrial Dysfunction, Inflammaging, and Cellular Senescence

Musculoskeletal aging is characterized by progressive deterioration of skeletal muscle, bone, and connective tissues, resulting in reduced physical function, increased risk of falls and fractures, and loss of independence. Mitochondrial dysfunction, chronic low-grade inflammation (inflammaging), and cellular senescence are recognized contributors to this process, although their relative importance varies among tissues and clinical phenotypes. This critical narrative review evaluates nutritional strategies that may influence these pathways and their relevance to age-related musculoskeletal decline. Evidence is synthesized for protein and amino acids, micronutrients, polyphenols, omega-3 fatty acids, gut-muscle-bone signaling, exercise-related myokines, and overall dietary patterns. Particular attention is given to their potential effects on mitochondrial homeostasis, inflammatory signaling, cellular senescence, muscle protein metabolism, and bone-muscle crosstalk. Findings from mechanistic studies, preclinical models, observational research, and clinical trials are critically appraised, with emphasis on differentiating biological plausibility from demonstrated clinical benefit. Although experimental evidence supports multiple mechanisms through which nutrition may modulate musculoskeletal aging, clinical outcomes remain heterogeneous and are influenced by nutritional status, age, health condition, intervention design, and physical activity. Improvements in molecular biomarkers do not necessarily translate into meaningful gains in strength, physical performance, or bone health. Nutritional interventions should therefore be considered components of multimodal healthy-aging strategies.