Background and Aim: Given the decline in satellite cell activation during aging, understanding effective strategies for regulating muscle stem cell differentiation and proliferation is essential for developing treatment strategies for muscle disorders. Exercise has been identified as an effective intervention to reduce age-related muscle mass and function loss. In addition, ginseng supplementation may play a role in activating and restoring satellite cell pools, especially in conjunction with exercise. Therefore, the aim of this study was to investigate the interactive effect of ginseng-purified exosome with endurance exercise on motor performance, muscle expression of CDK1 and Pax7 genes, and Pax7 protein concentration in aged rats.

Materials and Methods: Twenty male Wistar rats aged 16-20 months were randomly divided into 4 equal groups including control, aged + solvent (distilled water), aged + ginseng, aged + exercise, and aged + ginseng + exercise. Endurance training consisted of 30 minutes of continuous running on a treadmill without incline at a speed of 5 to 20 meters per minute with overload for 6 weeks, 5 sessions per week. Supplementation with purified exosomes from ginseng extract, 10 ml/kg body weight, was performed by gavage one hour before activity. 72 hours before sacrificing the samples, the cylinder functional test was performed to evaluate sensory motor function and spontaneous physical activity. Finally, the expression of CDK1 and Pax7 genes was measured by Real-time PCR and the relative abundance of Pax7 protein was measured by Western blot in the soleus muscle. The obtained data were analyzed using two-way ANOVA test at the P≤0.05 level.

Results: Endurance training and supplementation with purified ginseng-derived exosomes, each independently, resulted in significant increases in CDK1 gene expression (P = 0.001 for training; P = 0.007 for supplementation), Pax7 gene expression (P = 0.001 for both interventions), Pax7 protein concentration (P = 0.001 for both interventions), and significantly improved motor function (P = 0.001 for both interventions). However, no significant interactive effects of endurance training combined with ginseng supplementation were observed on CDK1 expression (P = 0.144), Pax7 expression (P = 0.188), Pax7 protein concentration (P = 0.861), or motor function (P = 0.592).

Conclusion: It appears that endurance training and ginseng-derived exosomes, each independently, may serve as effective strategies for counteracting age-related muscle atrophy, likely through increasing the expression of Pax7 and CDK1 and enhancing motor function. However, given the non-significant interactive effects of the two interventions, adding ginseng supplementation to an already effective training program may not confer additional benefits in boosting satellite cell markers or muscle endurance. This lack of synergy may be attributed to shared cellular signaling pathways underlying both interventions.