Targeting muscle–vasculature crosstalk in aging through the integrative roles of L-citrulline, leucine, and exercise: focus on muscle metabolism, vascular function, and sarcopenia prevention

Aging is characterized by a gradual deterioration in skeletal muscle mass, strength, and vascular functionality, which ultimately leads to the development of sarcopenia and the subsequent loss of physical autonomy. Nutritional and exercise-based interventions that specifically address this interplay may offer viable, non-pharmacological approaches to maintaining both muscular and vascular integrity. L-citrulline (CIT), recognized as a precursor to nitric oxide (NO), has been demonstrated to enhance endothelial functionality, improve oxygen transport, and increase muscle perfusion, while leucine has been shown to stimulate muscle protein synthesis. Furthermore, exercise serves to modulate both NO availability and anabolic signaling pathways, thereby amplifying the effects of these amino acids. Recent clinical and experimental research indicates that the concurrent administration of CIT and leucine supplementation, in conjunction with structured exercise regimens, yields superior enhancements in muscle mass, vascular reactivity, and physical performance compared to isolated interventions alone. The aforementioned synergistic effects are facilitated through a comprehensive regulation of mitochondrial biogenesis, alongside a reduction in inflammation and oxidative stress. This review consolidates existing empirical evidence regarding the collective contributions of CIT, leucine, and physical exercise in fostering healthy aging, while also delineating prospective research avenues for the formulation of personalized nutritional and physical strategies aimed at enhancing both muscular and vascular well-being in the elderly population.