Synergistic Effects of High-Intensity Interval Training and Resveratrol Supplementation on AKT, GDF-۱۱, and HIF-۱α Molecular Pathways in the Cardiac Tissue of Aged Wistar Rats

Background: Aging, as a major factor in endothelial dysfunction, seriously impairs microvascular perfusion. This study aimed to investigate the synergistic effects of high-intensity interval training (HIIT) and resveratrol supplementation on the expression of key molecular markers, GDF-۱۱, AKT, and HIF-۱α, in the cardiac tissue of aged Wistar rats. Materials and Methods: Twenty-four ۱۵-month-old male rats were randomly divided into sedentary control, HIIT only, resveratrol only, and HIIT+resveratrol groups (n=۶ per group). The HIIT protocol involved eight weeks of progressive treadmill running, while resveratrol (۱۵ mg/kg/day) was orally administered during the same period. Cardiac tissue was harvested ۲۴ hours after the intervention, and protein expression levels were analyzed using Western blotting. Results: Two-way ANOVA revealed that both exercise and resveratrol significantly influenced the expression of all three markers, with exercise emerging as the dominant factor. GDF-۱۱ expression demonstrated the highest upregulation in the HIIT+resveratrol group (P<۰.۰۰۱), while resveratrol alone had no significant effect. AKT levels were considerably elevated by exercise (F=۲۱۰۲.۴۶۳, η²=۰.۹۹۱) and further enhanced by resveratrol in exercised animals (P<۰.۰۰۱). Similarly, HIF-۱α expression noticeably increased across all intervention groups, with the highest expression in the combined group. Although resveratrol had an independent effect, its influence was markedly amplified when combined with HIIT. Conclusion: Our findings highlight the synergistic interaction between exercise and resveratrol in modulating cardioprotective pathways. The combined intervention can notably enhance molecular markers linked to angiogenesis, mitochondrial function, and oxidative stress resistance, offering promising therapeutic insights for mitigating age-related cardiac decline.