REVIEW article
Front. Aging Neurosci.
Sec. Neurocognitive Aging and Behavior
The Brain-Gut-Muscle Axis: A Mechanism for Exercise-Mediated Protection in Brain Aging
Wenyu Sun 1
WanHong Wang 2
Huifen Liu 1
Yu Zhang 1
Linlin Li 1
Bin Liu 1
1. Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
2. Shandong College of Traditional Chinese Medicine, Yantai, China
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Abstract
The global challenge of population aging underscores the critical need to delay brain aging and cognitive decline, a pressing public health issue. The brain-gut-muscle axis is a complex regulatory network connecting skeletal muscle, gut microbiota, and the brain. It has received considerable research attention for its crucial role in maintaining brain health and counteracting aging. As a safe and effective non-pharmacological intervention, exercise modulates gut microbiota composition and diversity and promotes the secretion of myokines from skeletal muscle. These actions, in turn, influence neural plasticity, inflammatory responses, and cognitive function. This review summarizes the mechanisms mediated by exercise within the brain-gut-muscle axis. We focus on: 1) how exercise dynamically regulates gut microbiota; 2) the interplay between myokines and gut microbiota; 3) the neuroprotective role of myokines; and 4) the potential mechanisms of the brain-muscle and gut-muscle pathways. Finally, we integrate these findings to present a synthesized view of how exercise delays brain aging through the brain-gut-muscle axis.
Summary
Keywords
Brain aging, Brain-gut-muscle axis, Exercise, Gut Microbiota, Myokines, Neuroinflammation, Oxidative Stress
Received
06 December 2025
Accepted
18 February 2026
Copyright
© 2026 Sun, Wang, Liu, Zhang, Li and Liu. 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: Bin Liu
Disclaimer
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.