Department of Morphology Surgery and Experimental Medicine, Section of Pathology Oncology and Experimental Biology, Interdisciplinary Center for the Study of Inflammation (ICSI), Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, Ferrara, Italy.
Department of Biochemistry, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland.
Int Rev Cell Mol Biol. 2018;340:209-344. doi: 10.1016/bs.ircmb.2018.05.006. Epub 2018 Jun 22.
Aging has been linked to several degenerative processes that, through the accumulation of molecular and cellular damage, can progressively lead to cell dysfunction and organ failure. Human aging is linked with a higher risk for individuals to develop cancer, neurodegenerative, cardiovascular, and metabolic disorders. The understanding of the molecular basis of aging and associated diseases has been one major challenge of scientific research over the last decades. Mitochondria, the center of oxidative metabolism and principal site of reactive oxygen species (ROS) production, are crucial both in health and in pathogenesis of many diseases. Redox signaling is important for the modulation of cell functions and several studies indicate a dual role for ROS in cell physiology. In fact, high concentrations of ROS are pathogenic and can cause severe damage to cell and organelle membranes, DNA, and proteins. On the other hand, moderate amounts of ROS are essential for the maintenance of several biological processes, including gene expression. In this review, we provide an update regarding the key roles of ROS-mitochondria cross talk in different fundamental physiological or pathological situations accompanying aging and highlighting that mitochondrial ROS may be a decisive target in clinical practice.
衰老是与几种退化过程相关联的，这些过程通过分子和细胞损伤的积累，可能逐渐导致细胞功能障碍和器官衰竭。人类衰老与个体患癌症、神经退行性疾病、心血管疾病和代谢紊乱的风险增加有关。过去几十年来，理解衰老和相关疾病的分子基础一直是科学研究的主要挑战之一。线粒体是氧化代谢的中心和活性氧（ROS）产生的主要部位，在许多疾病的健康和发病机制中都至关重要。氧化还原信号对于细胞功能的调节很重要，并且有几项研究表明 ROS 在细胞生理学中具有双重作用。事实上，高浓度的 ROS 是致病的，并会对细胞和细胞器膜、DNA 和蛋白质造成严重损伤。另一方面，适量的 ROS 对于维持包括基因表达在内的多种生物过程是必需的。在这篇综述中，我们提供了关于 ROS-线粒体相互作用在衰老伴随的不同基本生理或病理情况下的关键作用的最新信息，并强调线粒体 ROS 可能是临床实践中的一个决定性目标。
