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Exercise-regulated bone-brain axis: A novel perspective on age-related cognitive decline
Yubo Zhao1,2,3, Shuyu Liu1,2,3, Zhenxiang Sun1,2,3
1Department of Human Anatomy, School of Basic Medicine, Shenyang Medical College, Shenyang, Liaoning Province, China.
Neural Regeneration Research
|May 27, 2026
Summary
Exercise benefits brain health by influencing the bone-brain axis, a network connecting bone and brain signals. This pathway offers new ways to protect against age-related cognitive decline and dementia.
Area of Science:
- Neuroscience
- Gerontology
- Endocrinology
Background:
- Aging is a primary risk factor for cognitive decline and dementia.
- Exercise is a non-pharmacological intervention that delays cognitive decline and reduces dementia risk.
- Exercise impacts key signaling pathways like brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF), promoting neurogenesis and synaptic plasticity while reducing neuroinflammation.
Purpose of the Study:
- To review research on the bone-brain axis and its role in aging and cognitive decline.
- To explore how exercise modulates the bone-brain axis for cognitive protection.
- To identify potential therapeutic strategies for preventing age-related cognitive decline.
Main Methods:
- Literature review summarizing current research on the bone-brain axis.
- Analysis of studies investigating exercise's effects on bone-derived factors and brain function.
- Exploration of the interplay between bone, brain, and other systems in aging.
Main Results:
- The bone-brain axis is a bidirectional network where bone-derived factors (e.g., osteocalcin, FGF23) influence brain function.
- Exercise enhances the release of bone-derived signals like osteocalcin and irisin.
- These signals improve cognitive and emotional states, offering physiological mechanisms for exercise's cognitive benefits.
Conclusions:
- The bone-brain axis provides novel physiological mechanisms underlying exercise's protective effects on cognition.
- Modulating the bone-brain axis through exercise presents potential therapeutic avenues for cognitive health in aging.
- Future research should focus on personalized exercise and combined strategies for optimal cognitive aging.
Keywords:
agingbone–brain axisbrain-derived neurotrophic factorcognitive declinedementiaexerciseneuroregenerationosteocalcinMore Related Videos
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