Division of Genetics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School , Boston, Massachusetts.
Antioxid Redox Signal. 2013 Oct 20;19(12):1362-72. doi: 10.1089/ars.2012.4891. Epub 2012 Sep 20.
Redox biology is a rapidly developing area of research due to the recent evidence for general importance of redox control for numerous cellular functions under both physiological and pathophysiological conditions. Understanding of redox homeostasis is particularly relevant to the understanding of the aging process. The link between reactive oxygen species (ROS) and accumulation of age-associated oxidative damage to macromolecules is well established, but remains controversial and applies only to a subset of experimental models. In addition, recent studies show that ROS may function as signaling molecules and that dysregulation of this process may also be linked to aging.
Many protein factors and pathways that control ROS production and scavenging, as well as those that regulate cellular redox homeostasis, have been identified. However, much less is known about the mechanisms by which redox signaling pathways influence longevity. In this review, we discuss recent advances in the understanding of the molecular basis for the role of redox signaling in aging.
Recent studies allowed identification of previously uncharacterized redox components and revealed complexity of redox signaling pathways. It would be important to identify functions of these components and elucidate how distinct redox pathways are integrated with each other to maintain homeostatic balance.
Further characterization of processes that coordinate redox signaling, redox homeostasis, and stress response pathways should allow researchers to dissect how their dysregulation contributes to aging and pathogenesis of various age-related diseases, such as diabetes, cancer and neurodegeneration.
由于近年来有证据表明，在生理和病理条件下，氧化还原控制对许多细胞功能都具有重要意义，因此氧化还原生物学是一个迅速发展的研究领域。对氧化还原平衡的理解对于理解衰老过程尤其重要。活性氧（ROS）与与年龄相关的大分子氧化损伤积累之间的联系已经得到充分证实，但仍然存在争议，并且仅适用于一部分实验模型。此外，最近的研究表明，ROS 可以作为信号分子发挥作用，并且该过程的失调也可能与衰老有关。
已经鉴定出许多控制 ROS 产生和清除以及调节细胞氧化还原平衡的蛋白质因子和途径。然而，对于氧化还原信号通路如何影响寿命的机制知之甚少。在这篇综述中，我们讨论了氧化还原信号在衰老中的作用的分子基础的最新研究进展。
最近的研究允许鉴定以前未表征的氧化还原成分，并揭示了氧化还原信号通路的复杂性。确定这些成分的功能以及阐明不同的氧化还原途径如何相互整合以维持动态平衡将是很重要的。
进一步描述协调氧化还原信号、氧化还原平衡和应激反应途径的过程，应该使研究人员能够剖析其失调如何导致各种与年龄相关的疾病（如糖尿病、癌症和神经退行性变）的衰老和发病机制。
