Kalykaki Maria, Rubio-Tomás Teresa, Tavernarakis Nektarios
Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology - Hellas, Heraklion, Crete GR-70013, Greece.
Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology - Hellas, Heraklion, Crete GR-70013, Greece; Division of Basic Sciences, School of Medicine, University of Crete, Heraklion, Crete GR-71003, Greece.
Mech Ageing Dev. 2024 Dec;222:111993. doi: 10.1016/j.mad.2024.111993. Epub 2024 Sep 20.
Ageing is accompanied by a persistent, low-level inflammation, termed "inflammageing", which contributes to the pathogenesis of age-related diseases. Mitochondria fulfil multiple roles in host immune responses, while mitochondrial dysfunction, a hallmark of ageing, has been shown to promote chronic inflammatory states by regulating the production of cytokines and chemokines. In this review, we aim to disentangle the molecular mechanisms underlying this process. We describe the role of mitochondrial signalling components such as mitochondrial DNA, mitochondrial RNA, N-formylated peptides, ROS, cardiolipin, cytochrome c, mitochondrial metabolites, potassium efflux and mitochondrial calcium in the age-related immune system activation. Furthermore, we discuss the effect of age-related decline in mitochondrial quality control mechanisms, including mitochondrial biogenesis, dynamics, mitophagy and UPR, in inflammatory states upon ageing. In addition, we focus on the dynamic relationship between mitochondrial dysfunction and cellular senescence and its role in regulating the secretion of pro-inflammatory molecules by senescent cells. Finally, we review the existing literature regarding mitochondrial dysfunction and inflammation in specific age-related pathological conditions, including neurodegenerative diseases (Alzheimer's and Parkinson's disease, and amyotrophic lateral sclerosis), osteoarthritis and sarcopenia.
衰老伴随着一种持续的、低水平的炎症，称为“炎症衰老”，它促进了与年龄相关疾病的发病机制。线粒体在宿主免疫反应中发挥多种作用，而线粒体功能障碍作为衰老的一个标志，已被证明可通过调节细胞因子和趋化因子的产生来促进慢性炎症状态。在这篇综述中，我们旨在厘清这一过程背后的分子机制。我们描述了线粒体信号成分，如线粒体DNA、线粒体RNA、N-甲酰化肽、活性氧、心磷脂、细胞色素c、线粒体代谢物、钾外流和线粒体钙在与年龄相关的免疫系统激活中的作用。此外，我们讨论了线粒体质量控制机制（包括线粒体生物发生、动力学、线粒体自噬和未折叠蛋白反应）随年龄增长而下降对衰老炎症状态的影响。此外，我们关注线粒体功能障碍与细胞衰老之间的动态关系及其在调节衰老细胞分泌促炎分子中的作用。最后，我们综述了现有关于特定年龄相关病理状况（包括神经退行性疾病（阿尔茨海默病、帕金森病和肌萎缩侧索硬化症）、骨关节炎和肌肉减少症）中线粒体功能障碍与炎症的文献。
