Exercise intensity matters: A review on evaluating the effects of aerobic exercise intensity on muscle‐derived neuroprotective myokines

Abstract Exercise as a medical intervention is effective to help prevent and manage many chronic and complex diseases, including dementia. There is evidence to suggest that regular aerobic exercise protects against age‐related brain atrophy and reduces the risk of cognitive decline. The mechanisms b...

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Main Authors: Navabeh Zare, David J. Bishop, Itamar Levinger, Mark A. Febbraio, James R. Broatch
Format: Article
Language:English
Published: Wiley 2025-01-01
Series:Alzheimer’s & Dementia: Translational Research & Clinical Interventions
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Online Access:https://doi.org/10.1002/trc2.70056
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Summary:Abstract Exercise as a medical intervention is effective to help prevent and manage many chronic and complex diseases, including dementia. There is evidence to suggest that regular aerobic exercise protects against age‐related brain atrophy and reduces the risk of cognitive decline. The mechanisms by which exercise infers a neuroprotective effect remain to be established but may be related to a maintenance of brain volume and neuronal survival, improved cerebrovascular density and function, and/or increased synaptic plasticity. In addition, there is growing evidence to suggest the beneficial effects of exercise on brain health and cognitive function are, at least in part, mediated by factors released by skeletal muscle during contraction. The fact that the brain responds to exercise suggests that muscle‐derived peripheral factors, or “myokines,” may play a key role in muscle–brain crosstalk and exercise neuroprotection. However, the most effective “dose” of aerobic exercise to promote beneficial changes in these myokine pathways is currently unknown. Specifically, most of the evidence to date is from studies that have used moderate‐intensity exercise, and research investigating the merit of high‐intensity exercise is scarce. Considering the well‐established role of high‐intensity interval training in protecting against numerous medical conditions, more research is needed to identify the most effective “dose” of exercise to improve the beneficial effects of these myokines. Highlights Neuroprotection through exercise: Regular aerobic exercise mitigates age‐related brain atrophy and cognitive decline via multiple mechanisms, including brain volume maintenance, improved cerebrovascular function, and synaptic plasticity. Myokines as mediators: Muscle‐derived factors (myokines) play a crucial role in muscle–brain crosstalk, significantly contributing to the neuroprotective effects of exercise. Intensity matters: The review underscores the necessity to define and study exercise intensity, revealing high‐intensity exercise may be as effective, if not more, in promoting neuroprotective myokine levels compared to moderate‐intensity exercise. Future research directions: This review emphasizes the need for well‐controlled studies to explore the optimal exercise dose for enhancing myokine pathways and their implications for neurodegenerative disease prevention.
ISSN:2352-8737