# The brain-gut-muscle axis: a mechanism for exercise-mediated protection in brain aging

**Authors:** Wenyu Sun, WanHong Wang, Yu Zhang, Huifen Liu, Linlin Li, Yang Zhang, Bin Liu

PMC · DOI: 10.3389/fnagi.2026.1761832 · Frontiers in Aging Neuroscience · 2026-03-04

## TL;DR

Exercise helps protect the aging brain by connecting muscles, gut bacteria, and the brain through a complex system.

## Contribution

This review provides a synthesized understanding of how exercise delays brain aging via the brain-gut-muscle axis.

## Key findings

- Exercise modulates gut microbiota composition and diversity.
- Myokines from muscles have neuroprotective effects.
- The brain-gut-muscle axis plays a key role in cognitive health.

## 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.

## Full-text entities

- **Diseases:** inflammatory (MESH:D007249), cognitive decline (MESH:D003072)

## Full text

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## Figures

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## References

92 references — full list in the complete paper: https://tomesphere.com/paper/PMC12995645/full.md

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Source: https://tomesphere.com/paper/PMC12995645