The multifaceted impact of physical exercise on FoxO signaling pathways

The multifaceted impact of physical exercise on FoxO signaling pathways

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, inclu...

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Bibliographic Details
Main Authors: Wei Liu, Pengjun Meng, Zhi Li, Yifei Shen, Xin Meng, Shen Jin, Mengdi Hu
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-08-01
Series:Frontiers in Cell and Developmental Biology
Subjects:
FoxO signaling pathways
physical exercise
metabolic regulation
skeletal muscle
complex
left
Online Access:https://www.frontiersin.org/articles/10.3389/fcell.2025.1614732/full
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Summary: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.
ISSN:2296-634X

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