Oxidative Stress & Inflammation in Aging: Insights from Sickle Cell Disease

描述(申请人提供)：血管炎症和氧化应激正在迅速成为衰老科学的关键组成部分。然而，在目前的研究中，这两个实体之间的相互作用往往没有得到解决。为了解决这些问题，需要对导致血管闭塞的氧化应激和血管炎症的病理生理学有一个基本的了解。缩小这一知识差距将是这项提案的重点。我们将以镰状细胞病为模型，研究衰老过程中溶血、氧化应激、血管炎症和血管闭塞之间的联系。我们将学习大自然对过量血红素负担的保护性反应，HO-1的诱导。我们将通过调节HO-1来降低氧化应激和血管炎症，防止血管闭塞。这些研究将产生可以减少氧化应激和血管炎症的新疗法。预防血管闭塞将保护器官功能，提高生活质量，降低发病率和死亡率。该提案支持NIA的使命，将重点放在开发和评估与预防和治疗氧化应激和血管炎症相关的创新疗法的研究上。这项建议将通过提供对溶血、血管炎症、氧化应激和血管闭塞之间的联系的清楚了解来推动该领域的发展。

DESCRIPTION (provided by applicant): Vascular inflammation and oxidative stress are fast becoming key components of aging science. However, the interaction been these two entities is often not addressed in current research. To address these issues, a basic understanding of the pathophysiology of oxidative stress and vascular inflammation that results in vaso-occlusion is required. Closing this gap in knowledge will be the focus of this proposal. We will examine the link between hemolysis, oxidative stress, vascular inflammation and vaso-occlusion during aging using sickle cell disease as a model. We will learn from nature's protective response to excessive heme burden, the induction of HO-1. We will modulate HO-1 to decrease oxidative stress and vascular inflammation and prevent vaso-occlusion. New therapies which can decrease oxidative stress and vascular inflammation will result from these studies. Preventing vaso-occlusion will protect organ function, improve quality of life, and reduce morbidity and mortality. This proposal supports the mission of NIA by its focus on research that will develop and evaluate innovative treatments related to the prevention and treatment of oxidative stress and vascular inflammation. This proposal will advance the field by providing a clear understanding of the link between hemolysis, vascular inflammation, oxidative stress, and vaso-occlusion.