Department Physiology, School of Medicine and Dentistry, University of Valencia, Av. Blasco IbANez, 13. 46010 Valencia, Spain.
FIHCUV-INCLIVA, Valencia, Spain.
Curr Pharm Des. 2018;24(40):4755-4770. doi: 10.2174/1381612824666190114164117.
Cell senescence constitutes a critical process to respond to a variety of insults and adverse circumstances. Senescence involves the detention of DNA replication and cell proliferation, and hence, genetic programs associated with DNA damage response, chromosome stability, chromatin rearrangement, epigenetic reprogramming, and cell cycle are tightly linked to the senescent phenotype. Although senescence increases with age, the real implication of senescence regulation in the progress of aging in humans is largely discussed. In this context, reactive oxygen species (ROS) accumulation has also been postulated to play a critical role in cell homeostasis, aging processes, and control of proliferation.
The previous years have produced a high increase in data that refine our understanding of the role of ROS, and their relationship with epigenetic events, in determining cellular fate.
The accumulating evidence regarding the epigenetic regulation of ROS-mediated processes provides promising tools to deepen in our comprehension of the process of senescence, and to develop novel therapeutic strategies. In this review, we aim to provide an overview of the relationships between oxidative stress and cell senescence.
We provide information about the role of epigenetic regulation in senescence and aging, collecting recent data from some examples of progeroid syndromes in which cell senescence, oxidative stress and epigenetic mechanisms are severely impaired. Finally, a collection of data is presented regarding current pharmacological approaches that either target or use oxidative stress-related factors or epigenetic regulators as strategies for disease treatment.
细胞衰老构成了应对各种损伤和不利环境的关键过程。衰老涉及 DNA 复制和细胞增殖的阻滞，因此，与 DNA 损伤反应、染色体稳定性、染色质重排、表观遗传重编程和细胞周期相关的遗传程序与衰老表型紧密相关。尽管衰老会随着年龄的增长而增加，但衰老调节对人类衰老进程的真正意义在很大程度上仍存在争议。在这种情况下，活性氧（ROS）的积累也被认为在细胞内稳态、衰老过程和增殖控制中发挥着关键作用。
过去几年的数据大量增加，这些数据使我们对 ROS 的作用及其与表观遗传事件的关系有了更深入的了解，从而确定了细胞命运。
ROS 介导的过程的表观遗传调控方面的积累证据为深入了解衰老过程并开发新的治疗策略提供了有希望的工具。在这篇综述中，我们旨在概述氧化应激与细胞衰老之间的关系。
我们提供了关于表观遗传调控在衰老和衰老中的作用的信息，收集了一些早衰综合征的最新数据，这些综合征中细胞衰老、氧化应激和表观遗传机制严重受损。最后，还介绍了一些当前的药理学方法的数据，这些方法要么针对氧化应激相关因素，要么针对表观遗传调节剂，作为疾病治疗的策略。
