What does this research mean for the field?

High-Intensity Interval Training combined with resveratrol supplementation significantly increases GDF-11 expression levels in the cardiac tissue of aged Wistar rats. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.SUPPORTS_CONSENSUS.

What question did this study set out to answer?

To investigate the combined effects of high-intensity interval training and resveratrol on key molecular markers in cardiac tissue of aged rats.

February 8, 2026Disease and Diagnosis0 citationsOpen Access

Synergistic Effects of High-Intensity Interval Training and Resveratrol Supplementation on AKT, GDF-11, and HIF-1α Molecular Pathways in the Cardiac Tissue of Aged Wistar Rats

RRRaheleh RazieeIslamic Azad University, Tehran LMLida MoradiYale University BABahram AbediIslamic Azad University, Tehran

Key Result

Combined HIIT and resveratrol significantly upregulated cardiac GDF-11, AKT, and HIF-1α pathways in aged rats, with P<0.001 and exercise as the dominant factor.

Key Points

To investigate the combined effects of high-intensity interval training and resveratrol on key molecular markers in cardiac tissue of aged rats.
Divided 24 aged Wistar rats into four groups: control, HIIT only, resveratrol only, and HIIT+resveratrol.
Administered HIIT protocol over eight weeks with treadmill running and resveratrol supplementation.
Analyzed cardiac tissue for protein expression levels using Western blotting after intervention.
HIIT and resveratrol significantly affected expressions of GDF-11, AKT, and HIF-1α.
GDF-11 had the highest increase in the combined HIIT+resveratrol group (P<0.001).
AKT levels were significantly elevated by exercise, with additional increases when paired with resveratrol (P<0.001).
HIF-1α expression increased across all groups, peaking in the HIIT+resveratrol group.

Structured PICO

Does combined high-intensity interval training and resveratrol supplementation increase the expression of cardioprotective molecular markers (GDF-11, AKT, HIF-1α) in the cardiac tissue of aged Wistar rats?

Population

24 male Wistar rats, aged approximately 15 months, weighing between 280 g and 320 g.

Intervention

High-intensity interval training (HIIT) via progressive treadmill running (6 times per week) combined with oral resveratrol (15 mg/kg/day) for 8 weeks.

Comparator

Sedentary control receiving an equivalent volume of vehicle only (distilled water containing 0.5% carboxymethyl cellulose).

Outcome

Protein expression levels of GDF-11, AKT, and HIF-1α in cardiac tissue measured via Western blotting 24 hours after the 8-week intervention.surrogate

Combined high-intensity interval training and resveratrol supplementation synergistically enhances cardioprotective molecular pathways linked to angiogenesis and mitochondrial function in aged rat hearts.

Main Result

Absolute Event Rate: 0% vs 0%

Abstract

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-11, AKT, and HIF-1α, in the cardiac tissue of aged Wistar rats. Materials and Methods: Twenty-four 15-month-old male rats were randomly divided into sedentary control, HIIT only, resveratrol only, and HIIT+resveratrol groups (n=6 per group). The HIIT protocol involved eight weeks of progressive treadmill running, while resveratrol (15 mg/kg/day) was orally administered during the same period. Cardiac tissue was harvested 24 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-11 expression demonstrated the highest upregulation in the HIIT+resveratrol group (P<0.001), while resveratrol alone had no significant effect. AKT levels were considerably elevated by exercise (F=2102.463, η²=0.991) and further enhanced by resveratrol in exercised animals (P<0.001). Similarly, HIF-1α 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.

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