Tu Junbiao
Physical Education College of Luoyang Normal University, Henan Province, Luoyang, 471934, China.
Mol Neurobiol. 2025 Jun 13. doi: 10.1007/s12035-025-05121-y.
Age-related central nervous system (CNS) disorders, including neurodegenerative diseases, represent a growing global health burden. Mitochondrial dysfunction is a recognized hallmark in the pathogenesis of these conditions, emphasizing the critical importance of maintaining neuronal energy homeostasis and cellular integrity. Mitochondrial biogenesis, the dynamic process of generating new, functional mitochondria, is paramount for neuronal health and resilience against age-related decline. This review investigates the therapeutic potential of physical activity and polyphenols in modulating mitochondrial biogenesis and offering neuroprotection within the context of age-related CNS disorders. We explore how regular exercise profoundly impacts the brain by enhancing synaptic plasticity, promoting neurogenesis via neurotrophic factors like BDNF, and stimulating mitochondrial biogenesis through pathways such as PGC-1alpha activation. These adaptations collectively improve cognitive function and bolster neuronal resistance to damage. Concurrently, polyphenols, known for their antioxidant and anti-inflammatory properties, demonstrate significant neuroprotective effects. They are capable of crossing the blood-brain barrier and influencing key neuronal signaling pathways, directly stimulating mitochondrial biogenesis, and mitigating oxidative stress, thereby supporting neuronal survival. By synthesizing current evidence, this review highlights the complementary and potentially synergistic roles of exercise and polyphenols in preserving mitochondrial health and function in the CNS. The combined impact of these interventions offers a promising non-pharmacological strategy to combat age-related neurodegeneration. Future research should focus on optimizing exercise protocols and polyphenol interventions in human trials to maximize their neurotherapeutic benefits for CNS disorders.
与年龄相关的中枢神经系统（CNS）疾病，包括神经退行性疾病，在全球范围内构成了日益沉重的健康负担。线粒体功能障碍是这些疾病发病机制中公认的一个标志，这凸显了维持神经元能量稳态和细胞完整性的至关重要性。线粒体生物合成，即产生新的、功能性线粒体的动态过程，对于神经元健康以及抵御与年龄相关的衰退至关重要。本综述研究了体育活动和多酚类物质在调节线粒体生物合成以及在与年龄相关的中枢神经系统疾病背景下提供神经保护方面的治疗潜力。我们探讨了定期锻炼如何通过增强突触可塑性、通过脑源性神经营养因子（BDNF）等神经营养因子促进神经发生以及通过诸如激活PGC-1α等途径刺激线粒体生物合成，从而对大脑产生深远影响。这些适应性变化共同改善认知功能并增强神经元对损伤的抵抗力。同时，以其抗氧化和抗炎特性而闻名的多酚类物质具有显著的神经保护作用。它们能够穿过血脑屏障并影响关键的神经元信号通路，直接刺激线粒体生物合成并减轻氧化应激，从而支持神经元存活。通过综合当前证据，本综述强调了运动和多酚类物质在维持中枢神经系统线粒体健康和功能方面的互补及潜在协同作用。这些干预措施的综合影响为对抗与年龄相关的神经退行性变提供了一种有前景的非药物策略。未来的研究应专注于在人体试验中优化运动方案和多酚类物质干预措施，以最大程度地发挥它们对中枢神经系统疾病的神经治疗益处。
