Study summary · research use only
The multifaceted impact of physical exercise on FoxO signaling pathways
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
This review discusses literature on how physical exercise affects FoxO signaling pathways (FoxO1, FoxO3, FoxO4, FoxO6), described by the authors as central to cellular homeostasis, stress response, metabolism, and longevity, through mechanisms including phosphorylation, acetylation, and ubiquitination. The article discusses reported associations between exercise-driven FoxO modulation, via pathways such as PI3K/AKT, AMPK, SIRT1, and IGF-1, and insulin sensitivity, muscle hypertrophy, cardiovascular health, and neuroprotection, and reviews exercise's role in FoxO-related processes during muscle atrophy from pharmacological interventions, aging, disease, and diet. The authors describe understanding of exercise-FoxO interactions as offering insight relevant to developing future therapeutic strategies for disease progression.
Abstract
This review explores the multifaceted impact of physical exercise on FoxO signaling pathways, which play a central role in cellular homeostasis, stress response, metabolism, and longevity. Exercise influences FoxO proteins-particularly FoxO1, FoxO3, FoxO4, and FoxO6-through diverse mechanisms, including phosphorylation, acetylation, and ubiquitination, determining their localization, transcriptional activity, and stability. Regular exercise modulates FoxO signaling by activating pathways like PI3K/AKT, AMPK, SIRT1, and IGF-1, promoting cellular resilience against oxidative stress, apoptosis, and metabolic dysfunction. The review highlights how exercise-induced modulation of FoxO pathways contributes to improved insulin sensitivity, muscle hypertrophy, cardiovascular health, neuroprotection, and reduced risks of chronic diseases, including metabolic syndrome, neurodegeneration, cardiovascular disease, and cancer. Additionally, it addresses the role of exercise in preventing muscle atrophy under various conditions, such as pharmacological interventions, aging, disease, and dietary factors. By enhancing FoxO signaling, exercise promotes anabolic processes, mitochondrial function, autophagy, and antioxidant defenses. Understanding the intricate relationship between exercise and FoxO pathways offers insights into developing therapeutic strategies to mitigate disease progression.
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