Evaluation of Serum Autophagic Biomarkers in the Acute Response to Walking and Cycling in Healthy Male Individuals

Plain-language summary

Physical exercise (walking and cycling) is a potent physiological stimulus that simultaneously alters energy balance, mechanical loading, and metabolic demands in the organism. Autophagy is recognized as a fundamental mechanism in the regulation of acute cellular responses to such stimuli, playing a critical role in maintaining cellular homeostasis, removing damaged proteins and organelles, and ensuring metabolic adaptation \[1\]. Experimental and translational studies have demonstrated that particularly moderate-intensity and controlled mechanical loading can activate autophagic pathways, thereby supporting structural and functional adaptation in muscle, bone, and connective tissues \[2-4\]. In the current literature, the relationship between autophagy and exercise has largely been evaluated through experimental animal models and a limited number of human studies \[5\]. Although animal studies have clearly shown that physiological loading such as walking and running increases molecular signals associated with autophagy, the direct assessment of autophagy at the tissue level in humans is limited due to ethical and feasibility concerns, as it requires invasive methods (e.g., muscle biopsy) \[3\]. Therefore, recent human studies have increasingly focused on indirect evaluation of autophagy through peripheral blood mononuclear cells and circulating biomarkers \[6\]. Indeed, recent human studies have reported that proteins associated with autophagy may exhibit changes in peripheral blood cells or circulation in response to acute exercise, and that this response may vary depending on the type, intensity, and mechanical characteristics of the exercise \[6\]. These findings suggest that autophagy is not merely a tissue-specific process but can also be monitored at the systemic level as part of physiological adaptation \[7\]. However, there is a limited number of human studies that comparatively investigate the acute effects of different exercise modalities with distinct mechanical loading profiles (such as walking and cycling) on serum biomarkers related to autophagy. In this context, the present project aims to evaluate the acute effects of two common aerobic exercise modalities with different mechanical loading characteristics-walking and cycling-on serum biomarkers associated with autophagy in healthy male individuals. In this study, Beclin-1, LC3, and ATG3 levels will be considered not as direct indicators of autophagic flux in tissues, but as circulating biomarkers associated with the initiation and maintenance of autophagy. By examining changes in the serum levels of these proteins following acute exercise, it is aimed to obtain indirect yet biologically meaningful data regarding exercise-induced cellular adaptation mechanisms without the need for invasive procedures. In conclusion, this study aims to contribute to an important gap in the current literature by safely and ethically demonstrating the acute physiological responses related to autophagy in humans across exercise modalities with different mechanical characteristics, thereby enhancing our understanding of the exercise-autophagy relationship.

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