Resistance training as a modulator of autophagy in skeletal muscle: A systematic review of molecular mechanisms and adaptive responses

Autophagy is a tightly regulated intracellular degradation process essential for maintaining skeletal muscle homeostasis, particularly under metabolic stress, such as resistance exercise. This systematic review aimed to investigate the acute and chronic effects of resistance training on autophagy in skeletal muscle, emphasizing the modulation of key molecular pathways in animal and human models. The results indicate that resistance exercise induces autophagic responses with distinct temporal dynamics. Acute protocols have been shown to induce the activation of autophagy-associated genes and signaling pathways, including AMPK, ULK1, and FOXO3, resulting in transient increases in autophagic flux that facilitate cellular repair and restoration of homeostasis. In contrast, chronic resistance training elicited divergent responses across the studies analyzed. Some studies identified sustained autophagic activity parallel to activating anabolic pathways such as mTOR and AKT. Others reported reduced autophagic flux that favored protein accumulation and muscle hypertrophy. Modulation of autophagy has also been influenced by predominant muscle fiber type and biological sex, underscoring the complexity of its regulation. These findings collectively highlight resistance exercise as an effective autophagy modulator in skeletal muscle, contributing to cellular quality control and adaptive remodeling. Understanding the interplay between anabolic pathways and autophagic mechanisms may provide critical insights for optimizing exercise-based interventions to preserve muscle function, metabolic health, and tissue integrity over the long term.