Document Type : Original Article

Authors

• Marzieh Papisad ¹
• Abdollhamid Habibi ²
• Saeid Shakerian ²
• Mohammad Rami ³

¹ PhD Student in Exercise Physiology, Faculty of Sport Sciences, Shahid Chamran University of Ahvaz, Ahvaz, Iran.

² Professor at Department of Exercise Physiology, Faculty of Sport Sciences, Shahid Chamran University of Ahvaz, Ahvaz, Iran.

³ Assistant Professor at Department of Exercise Physiology, Faculty of Sport Sciences, Shahid Chamran University of Ahvaz, Ahvaz, Iran.

Abstract

Extended Abstract
Background and Aim: Sarcopenia is a prevalent age-related condition characterized by the progressive loss of skeletal muscle mass, strength, and function. This deterioration leads to significant health consequences, including impaired mobility, loss of independence, increased risk of falls, fractures, and even mortality (3). From a pathophysiological standpoint, sarcopenia is associated with multiple interrelated mechanisms, such as reduced satellite cell activity, chronic inflammation, oxidative stress, diminished muscle protein synthesis, and impaired  neuromuscular signaling (1, 4). Several key proteins have been identified as crucial molecular indicators in the progression or reversal of sarcopenia. For instance, Paired Box 7 (PAX7) is essential for satellite cell activation and muscle regeneration, and its reduction signals impaired muscle repair associated with aging (5). Nuclear factor kappa B (NF-κB), a central regulator of chronic inflammation, contributes to muscle atrophy and exhibits elevated activity in aged muscle tissue (7). Forkhead box O (FOXO3) is another essential factor involved in regulating apoptosis, autophagy, and protein turnover (10, 11). Additionally, Nicotinic acetylcholine receptor (nAChRs) play a critical role at the neuromuscular junction, facilitating nerve-to-muscle signaling; their reduction compromises muscle contraction and strength (14). While pharmacological interventions have shown limited efficacy in managing sarcopenia, exercise—particularly resistance and endurance training—has emerged as a safe and effective strategy. Resistance training primarily enhances muscular strength, whereas endurance training exerts anti-inflammatory effects and improves metabolic function (13, 17). Given these distinct but complementary mechanisms, the present study aimed to investigate and compare the effects of six weeks of resistance versus endurance training on the levels of four key proteins in the gastrocnemius muscle of female rats modeled with sarcopenia.
Materials and Methods: This experimental laboratory study was conducted on 20 adult female Wistar rats (aged 12 ± 1 weeks, weight 200–250 g). All animals were housed under standard environmental conditions (controlled temperature, humidity, and lighting) with ad libitum access to food and water. The rats were randomly assigned to four equal groups: (1) healthy control, (2) sarcopenic control, (3) sarcopenia + resistance training, and (4) sarcopenia + endurance training. Sarcopenia was induced by intraperitoneal injection of dexamethasone (0.1 mg/kg) for 10 consecutive days. Resistance training consisted of ladder climbing at an 80° incline with a 110 cm height, while carrying a load equivalent to 60% of body weight attached to the tail. This was performed three times weekly for six weeks. Endurance training involved treadmill running at moderate intensity (60–70% of maximum speed capacity), with gradual increases over the six-week period. At the end of the intervention period, animals were anesthetized using appropriate agents and euthanized. The gastrocnemius muscle of the hind limbs was dissected for protein analysis. Western blotting was used to quantify PAX7, NF-κB, FOXO3, and nAChR protein levels. For statistical analysis, data normality was assessed using the Shapiro–Wilk test, and homogeneity of variances was confirmed using Levene’s test. Group differences were analyzed using one-way ANOVA, followed by Tukey’s post hoc test for pairwise comparisons. Statistical significance was accepted at p<0.05.
Findings: Dexamethasone administration effectively induced sarcopenia in the model, as evidenced by significant reductions in body weight and decreased levels of PAX7 and nAChR, alongside marked increases in NF-κB and FOXO3. These alterations reflect activation of inflammatory and catabolic pathways, as well as impaired muscle regenerative capacity. Both resistance and endurance training significantly reversed these changes. PAX7 levels increased in both intervention groups, with endurance training producing a significantly greater enhancement, indicating more effective stimulation of satellite cells and muscle regeneration. NF-κB levels significantly decreased following endurance training, highlighting its potent anti-inflammatory effect. Conversely, FOXO3, which is associated with muscle degradation and cell death, was reduced in both exercise groups, with a greater reduction observed in the resistance training group, suggesting superior efficacy in inhibiting muscle catabolism. nAChR expression improved significantly in both training groups compared to the sarcopenic control, although no significant difference was found between resistance and endurance protocols. 
Conclusion: Overall, the results demonstrate that both resistance and endurance training confer beneficial effects on sarcopenia-related molecular pathways. Endurance training was more effective in stimulating muscle regeneration and attenuating inflammatory responses, whereas resistance training more strongly inhibited catabolic processes and supported neuromuscular stability. These differential adaptations highlight the potential for targeted exercise prescriptions to address specific pathophysiological aspects of sarcopenia.
This study demonstrates that both resistance and endurance training exert significant, beneficial effects on molecular markers associated with sarcopenia. Endurance training enhances muscle regeneration and reduces inflammation through increased PAX7 and decreased NF-κB, whereas resistance training more effectively suppresses muscle degradation via reduction of FOXO3. These distinctions highlight the potential for either modality to be used independently or in combination, depending on therapeutic objectives. The findings underscore the value of targeted physical exercise as a non-pharmacological, cost-effective, and safe strategy for managing sarcopenia. Future studies with larger sample sizes, prolonged intervention periods, and comprehensive molecular analyses are warranted to further clarify the mechanisms underlying exercise-induced muscle adaptations and optimize individualized treatment protocols for sarcopenia.
Ethical Considerations: All ethical principles in this research were meticulously adhered to by the researchers.
Funding: The authors of this article declare that they have not received any financial support from any organization.
Conflicts of interest: The authors report no conflicts of interest in relation to this manuscript.

Keywords

• Resistance training
• Aerobic endurance training
• Female rat
• Sarcopenia