MRC London Institute of Medical Sciences, Du Cane Road, London W12 0NN, U.K.
Institute of Clinical Sciences, Imperial College London, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, U.K.
Biochem Soc Trans. 2020 Apr 29;48(2):367-377. doi: 10.1042/BST20190052.
Ageing and age-related diseases are major challenges for the social, economic and healthcare systems of our society. Amongst many theories, reactive oxygen species (ROS) have been implicated as a driver of the ageing process. As by-products of aerobic metabolism, ROS are able to randomly oxidise macromolecules, causing intracellular damage that accumulates over time and ultimately leads to dysfunction and cell death. However, the genetic overexpression of enzymes involved in the detoxification of ROS or treatment with antioxidants did not generally extend lifespan, prompting a re-evaluation of the causal role for ROS in ageing. More recently, ROS have emerged as key players in normal cellular signalling by oxidising redox-sensitive cysteine residues within proteins. Therefore, while high levels of ROS may be harmful and induce oxidative stress, low levels of ROS may actually be beneficial as mediators of redox signalling. In this context, enhancing ROS production in model organisms can extend lifespan, with biological effects dependent on the site, levels, and specific species of ROS. In this review, we examine the role of ROS in ageing, with a particular focus on the importance of the fruit fly Drosophila as a powerful model system to study redox processes in vivo.
衰老和与年龄相关的疾病是我们社会的社会、经济和医疗保健系统面临的主要挑战。在众多理论中，活性氧（ROS）被认为是衰老过程的驱动因素。ROS 作为需氧代谢的副产物，能够随机氧化大分子，导致细胞内损伤随时间积累，最终导致功能障碍和细胞死亡。然而，ROS 解毒酶的基因过表达或抗氧化剂治疗通常不能延长寿命，这促使人们重新评估 ROS 在衰老中的因果作用。最近，ROS 通过氧化蛋白质中氧化还原敏感的半胱氨酸残基，成为正常细胞信号转导的关键参与者。因此，虽然高水平的 ROS 可能是有害的，并诱导氧化应激，但低水平的 ROS 实际上可能作为氧化还原信号转导的介质是有益的。在这种情况下，增强模型生物中的 ROS 产生可以延长寿命，其生物学效应取决于 ROS 的位置、水平和特定种类。在这篇综述中，我们研究了 ROS 在衰老中的作用，特别关注果蝇作为研究体内氧化还原过程的强大模型系统的重要性。
