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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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2025-08-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2025.1614732/full |
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| author | Wei Liu Pengjun Meng Zhi Li Yifei Shen Xin Meng Shen Jin Mengdi Hu |
| author_facet | Wei Liu Pengjun Meng Zhi Li Yifei Shen Xin Meng Shen Jin Mengdi Hu |
| author_sort | Wei Liu |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-b0276c6ae0b840b1adc94bd16a0aa0ea |
| institution | Kabale University |
| issn | 2296-634X |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj-art-b0276c6ae0b840b1adc94bd16a0aa0ea2025-08-20T03:59:35ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2025-08-011310.3389/fcell.2025.16147321614732The multifaceted impact of physical exercise on FoxO signaling pathwaysWei Liu0Pengjun Meng1Zhi Li2Yifei Shen3Xin Meng4Shen Jin5Mengdi Hu6Department of Physical Education, Xidian University, Xi’an, Shaanxi, ChinaDepartment of Physical Education, Xidian University, Xi’an, Shaanxi, ChinaDepartment of Physical Education, Xidian University, Xi’an, Shaanxi, ChinaDepartment of Physical Education, Xidian University, Xi’an, Shaanxi, ChinaDepartment of Physical Education, Xidian University, Xi’an, Shaanxi, ChinaOffice of Scientific Research, Ersha Sports Training Center of Guangdong Province, Guangzhou, Guangdong, ChinaGynecology Department, Shaanxi Provincial Hospital of Chinese Medicine, Xi’an, Shaanxi, ChinaThis 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.https://www.frontiersin.org/articles/10.3389/fcell.2025.1614732/fullFoxO signaling pathwaysphysical exercisemetabolic regulationskeletal musclecomplexleft |
| spellingShingle | Wei Liu Pengjun Meng Zhi Li Yifei Shen Xin Meng Shen Jin Mengdi Hu The multifaceted impact of physical exercise on FoxO signaling pathways Frontiers in Cell and Developmental Biology FoxO signaling pathways physical exercise metabolic regulation skeletal muscle complex left |
| title | The multifaceted impact of physical exercise on FoxO signaling pathways |
| title_full | The multifaceted impact of physical exercise on FoxO signaling pathways |
| title_fullStr | The multifaceted impact of physical exercise on FoxO signaling pathways |
| title_full_unstemmed | The multifaceted impact of physical exercise on FoxO signaling pathways |
| title_short | The multifaceted impact of physical exercise on FoxO signaling pathways |
| title_sort | multifaceted impact of physical exercise on foxo signaling pathways |
| topic | FoxO signaling pathways physical exercise metabolic regulation skeletal muscle complex left |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2025.1614732/full |
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