From Growth Trajectory to Functional Decline: Age-Contextualized Nutritional Strategies for Muscle Vulnerability. A...

Muscle vulnerability occurs at both extremes of the human lifespan, although its biological significance differs substantially between developmental growth and late-life decline. During childhood and adolescence, insufficient muscle accretion reflects disruption of physiological anabolic trajectories driven by inadequate energy availability, inflammatory burden, endocrine imbalance, or disease-associated catabolism. In older adults, muscle deterioration is characterized by anabolic resistance, neuromuscular remodeling, chronic low-grade inflammation, and hormonal decline, culminating in sarcopenia and loss of functional independence. The absence of harmonized diagnostic frameworks across age groups limits direct translational extrapolation. A lifespan-informed perspective distinguishing growth-supportive from function-preserving nutritional approaches is, therefore, required. This narrative review examines how major classes of nutritional bioactive interact with molecular pathways regulating skeletal muscle homeostasis in fragile populations across the lifespan. The analysis encompasses energy adequacy, protein quantity and quality, amino acid-dependent anabolic signaling, vitamin D status, lipid-derived mediators, redox-modulating phytochemicals, and micronutrients supporting mitochondrial bioenergetics. In pediatric contexts, nutritional interventions primarily aim to restore anabolic permissiveness within a structurally intact growth environment. In aging individuals, strategies focus on mitigating anabolic resistance through optimized protein intake, correction of micronutrient insufficiencies, and integration with resistance exercise to preserve functional capacity. This narrative review emphasizes the need to distinguish mechanistic rationale from clinically validated interventions, as improvements in molecular pathways do not consistently translate into meaningful functional outcomes.