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Mechanisms by Which Exercise Delays Brain Aging Through Regulation of the Mitochondrial Quality Control System
College of Physical Education, Yangzhou University, Yangzhou 225000, China
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Author to whom correspondence should be addressed.
Biology 2026, 15(11), 854; https://doi.org/10.3390/biology15110854 (registering DOI)
Submission received: 10 April 2026
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Revised: 12 May 2026
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Accepted: 27 May 2026
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Published: 29 May 2026
Simple Summary
Brain aging is a gradual process that leads to a decline in memory, learning ability, and overall cognitive function. A key factor underlying this process is the dysfunction of mitochondria, the structures responsible for producing energy inside brain cells. When mitochondrial function deteriorates, brain cells face energy shortages and increased damage, leading to faster neuronal loss and cognitive impairment, which accelerates neuronal degeneration and cognitive decline. Growing evidence shows that physical exercise is a powerful non-drug strategy to protect the aging brain. Regular exercise can improve mitochondrial health, enhance energy production, and support the brain’s ability to adapt to stress and aging-related changes. This review summarises current research showing how exercise helps maintain mitochondrial function, supports brain plasticity, and slows age-related cognitive decline. It also discusses how different types of exercise may have distinct benefits and highlights the potential of personalised exercise strategies for brain health. These findings provide a scientific basis for using exercise as an effective approach to promote healthy brain aging and to support the prevention and treatment of neurodegenerative diseases.
Abstract
Brain aging is a complex biological process characterised by progressive neuronal and synaptic decline, in which disruption of mitochondrial quality control plays a central role. This system encompasses multiple synergistic components, including mitochondrial biogenesis, dynamic equilibrium, autophagic clearance, and energy metabolism. Aging induces dysfunction across these processes, precipitating mitochondrial fragmentation, functional decline, and energy crises, ultimately driving cognitive deterioration. Exercise is a promising non-pharmacological intervention for preserving brain health during aging, and its benefits may be mediated, at least in part, through modulation of mitochondrial quality control. Specifically, exercise has been shown to activate key signaling pathways such as AMPK/SIRT1/PGC-1α, thereby promoting mitochondrial biogenesis and metabolic adaptation. It may also regulate mitochondrial dynamics and mitophagy via pathways including cAMP/PKA/Drp1 and AMPK/mTOR. In addition, emerging evidence indicates that exercise may influence brain mitochondrial function through activity-dependent regulation of mitochondrial gene expression and systemic signaling factors. Furthermore, this review discusses potential differences between exercise modalities and highlights future directions for personalised intervention strategies, providing a theoretical basis for the application of exercise in delaying brain aging and preventing neurodegenerative diseases.
