Steffan Davide, Pezzini Camilla, Esposito Martina, Franco-Romero Anais
Department of Biomedical Sciences, University of Padova, Via Ugo Bassi 58/B, 35131 Padova, Italy.
Veneto Institute of Molecular Medicine, Via Orus 2, 35129 Padova, Italy.
Biomolecules. 2025 Aug 29;15(9):1252. doi: 10.3390/biom15091252.
Mitochondrial aging plays a central role in the functional decline of the central nervous system (CNS), with profound consequences for neurological health. As the brain is one of the most energy-demanding organs, neurons are particularly susceptible to mitochondrial dysfunction that arises with aging. Key features of mitochondrial aging include impaired mitochondrial dynamics, reduced mitophagy, increased production of reactive oxygen species (ROS), and accumulation of mitochondrial DNA (mtDNA) mutations. These alterations dramatically compromise neuronal bioenergetics, disrupt synaptic integrity, and promote oxidative stress and neuroinflammation, paving the path for the development of neurodegenerative diseases. This review also examines the complex mechanisms driving mitochondrial aging in the central nervous system (CNS), including the disruption of mitochondrial-organelle communication, and explores how mitochondrial dysfunction contributes to neurodegenerative diseases, such as Alzheimer's, Parkinson's, Huntington's, and amyotrophic lateral sclerosis. By synthesizing current evidence and identifying key knowledge gaps, we emphasize the urgent need for targeted strategies to restore mitochondrial function, maintain cognitive health, and delay or prevent age-related neurodegeneration.
线粒体衰老在中枢神经系统（CNS）的功能衰退中起着核心作用，对神经健康产生深远影响。由于大脑是能量需求最高的器官之一，神经元特别容易受到衰老过程中出现的线粒体功能障碍的影响。线粒体衰老的关键特征包括线粒体动力学受损、线粒体自噬减少、活性氧（ROS）生成增加以及线粒体DNA（mtDNA）突变积累。这些改变极大地损害了神经元的生物能量学，破坏了突触完整性，并促进了氧化应激和神经炎症，为神经退行性疾病的发展铺平了道路。本综述还研究了驱动中枢神经系统（CNS）线粒体衰老的复杂机制，包括线粒体与细胞器通讯的破坏，并探讨了线粒体功能障碍如何导致神经退行性疾病，如阿尔茨海默病、帕金森病、亨廷顿病和肌萎缩侧索硬化症。通过综合当前证据并确定关键知识空白，我们强调迫切需要有针对性的策略来恢复线粒体功能、维持认知健康以及延缓或预防与年龄相关的神经退行性变。
