Departments of Surgery, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390, USA.
Aging Dis. 2014 Apr 1;5(2):137-49. doi: 10.14336/AD.2014.0500137. eCollection 2014 Apr.
The incidence of sepsis and its attendant mortality risk are significantly increased with aging. Thus, severe sepsis in the elderly is likely to become an emerging concern in critical care units. Cardiac dysfunction is an important component of multi-organ failure after sepsis. In our laboratory, utilizing a pneumonia-related sepsis animal model, our research has been focused on the mechanisms underlying sepsis-induced cardiac failure. In this review, based on findings from others and ours, we discussed age-dependent decay in mitochondria and the role of mitochondrial reactive oxygen species (mtROS) in sepsis-induced cardiac inflammation and autophagy. Our recent discovery of a potential signal transduction pathway that triggers myocardial mitochondrial damage is also discussed. Because of the significance of mitochondria damage in the aging process and in sepsis pathogenesis, we hypothesize that specific enhancing mitochondrial antioxidant defense by mitochondria-targeted antioxidants (MTAs) may provide important therapeutic potential in treating elder sepsis patients. In this review, we summarized the categories of currently published MTA molecules and the results of preclinical evaluation of MTAs in sepsis and aging models.
随着年龄的增长,脓毒症的发病率及其相关的死亡风险显著增加。因此,老年人严重脓毒症可能成为重症监护病房的一个新关注点。心功能障碍是脓毒症后多器官衰竭的一个重要组成部分。在我们的实验室中,利用肺炎相关性脓毒症动物模型,我们的研究集中在脓毒症诱导的心衰的机制上。在这篇综述中,基于他人和我们的研究结果,我们讨论了与年龄相关的线粒体功能下降以及线粒体活性氧(mtROS)在脓毒症诱导的心肌炎症和自噬中的作用。我们最近发现了一种潜在的信号转导途径,它可以触发心肌线粒体损伤,这也在讨论之中。由于线粒体损伤在衰老过程和脓毒症发病机制中的重要性,我们假设通过线粒体靶向抗氧化剂(MTAs)特异性增强线粒体抗氧化防御可能为治疗老年脓毒症患者提供重要的治疗潜力。在这篇综述中,我们总结了目前已发表的 MTA 分子的类别,以及 MTAs 在脓毒症和衰老模型中的临床前评估结果。