REVIEW article
Front. Cell Dev. Biol.
Sec. Signaling
Volume 13 - 2025 | doi: 10.3389/fcell.2025.1614732
The Multifaceted Impact of Physical Exercise on FoxO Signaling Pathways
Provisionally accepted
- 1Department of Physical Education, Xidian University, Xi’an 710126 , Shaanxi , China, Xi’an, China
- 2Ersha Sports Training Center of Guangdong Province, Guangzhou510100, Guangdong, China, Guangzhou, China
- 3Shaanxi Provincial Hospital of Chinese medicine, Xi'an 710003, Shaanxi , China, Xi'an, China
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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.
Keywords: FoxO Signaling Pathways, physical exercise, Metabolic Regulation, Skeletal Muscle Font: (Default) +Headings (Calibri), Complex Script Font: +Headings (Calibri) Normal, left
Received: 19 Apr 2025; Accepted: 02 Jul 2025.
Copyright: © 2025 Liu, Meng, Li, Shen, Meng, Jin and Hu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: MengDi Hu, Shaanxi Provincial Hospital of Chinese medicine, Xi'an 710003, Shaanxi , China, Xi'an, China
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