Exercise orchestrates systemic metabolic and neuroimmune homeostasis via the brain-muscle-liver axis to slow down aging and neurodegeneration: a narrative review.
Level 5 - mechanism / opinion, no new human data
Narrative review synthesizing mechanistic pathways without primary empirical data or systematic search methodology.
PubMed 40506775 · doi:10.1186/s40001-025-02751-9
What was done
The authors synthesized literature examining the role of physical exercise in regulating systemic metabolism and neuroimmune interactions via the brain-muscle-liver axis to counteract aging and neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease.
What was found
No empirical data, sample sizes, or quantitative effect estimates are reported in the abstract. The review describes several mechanistic pathways modulated by exercise, including AMPK/PGC-1α signaling in skeletal muscle, hepatic SIRT1 activation, NF-κB inhibition in the brain, enhanced BDNF and IL-6 signaling, Nrf2-driven antioxidant responses, and increased autophagy-mediated clearance of amyloid-beta and alpha-synuclein.
Why it matters
This review conceptualizes exercise as a systemic multi-organ coordinator that simultaneously targets metabolic, immunologic, and cellular degradation pathways involved in brain aging.
Limits
As a narrative review, it lacks a systematic search protocol, quality appraisal of included studies, and quantitative data synthesis. The discussed mechanisms largely reflect preclinical models, and clinical translation regarding specific exercise regimens, dosing, and predictive biomarkers remains unestablished.
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