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

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.