Aging and Oxidative Stress Influence Salivary Gland Disease in Sjogren's Syndrome

干燥综合征(SS)是一种慢性、衰弱的全身性自身免疫性疾病，患有多发性 器官系统。自身免疫和泪腺靶向外分泌唾液和泪腺 炎症反应导致器官功能障碍，导致液体分泌减少，这表现为 进入口干和眼干的紊乱症状。尽管报告的年龄范围很大， 在诊断时，众所周知，大多数SS患者年龄较大。为什么表型性状更多 在老年患者中是否有突出表现尚不清楚。老化的器官表现出高度的氧化应激，这通常是 与器官功能衰退有关。虽然，..SS患者表现出氧化增加的证据 应激标志物；氧化应激升高是致病因素还是炎性反应的结果 对患者的反应尚不清楚，调查具有挑战性。因此，根据已出版的文献和 我们的初步数据，这项提议将检验总体假设，即 自身免疫和衰老相关的氧化应激导致唾液腺疾病和 SS的功能障碍。这项提案的目标1将具体解决与衰老相关的假设 氧化应激使唾液腺更容易受到免疫介导的损害。在目标2中， 通过使用一种新的小鼠模型系统，我们将检验唾液中的氧化应激本身 腺上皮细胞不足以引起SS。这项建议的主要目标是理解 SS患者关键临床观察背后的机制：一年中临床症状的突出 高龄和氧化应激升高在疾病过程中的可能作用。理解 将衰老与SS器官功能障碍联系起来的基本机制将是开发新的 治疗这种疾病的方式。

Sjögren’s Syndrome (SS) is a chronic and debilitating systemic autoimmune disorder afflicting multiple organ systems. The targeting of the exocrine salivary and lacrimal glands by an autoimmune and inflammatory response leads to organ dysfunction causing reduced fluid secretion, which manifests into the dry mouth and dry eye symptoms of the disorder. Although a wide age range is reported in patients at diagnosis, it is well known that most SS patients are older. Why phenotypic traits are more prominent in older patients is unknown. Aging organs show heightened oxidative stress, which is often associated with declining organ function. Although,. SS patients show evidence of increased oxidative stress markers; whether elevated oxidative stress is causative or the outcome of an inflammatory response is unclear and challenging to investigate in patients. Hence based on published literature and our preliminary data, this proposal will test the overall hypothesis that the combined effects of autoimmunity and aging-associated oxidative stress contribute to salivary gland disease and dysfunction in SS. Aim 1 of this proposal will specifically address the hypothesis that aging-associated oxidative stress makes salivary glands more susceptible to immune-mediated damage. And in aim 2, by using a novel mouse model system, we will test the hypothesis that oxidative stress per se in salivary gland epithelial cells is insufficient to cause SS. The primary goal of this proposal is to understand the mechanisms behind key clinical observations in SS patients: prominence of clinical symptoms at an older age and the possible role of elevated oxidative stress in the disease process. Understanding basic mechanisms linking aging with organ dysfunction in SS will be essential in developing novel modalities to treat the disease.