Immune and metabolic dysfunction during aging in human cohorts

老年与代谢改变的高患病率有关，如2型糖尿病(DM)和前OM(直接称为血糖异常)，以及与较高的发展和死亡风险相关的免疫力下降 由于肺部感染，如肺结核(PTB)。这些免疫代谢的改变伴随着 由于其他器官系统(肺、脑、骨骼肌)衰竭，导致发病率和死亡率增加。 了解这些相互作用并及早发现它们对于延迟、预防或恢复 个人器官系统的健康。免疫代谢改变的潜在机制尚不清楚，但 我们对感染和不感染结核分枝杆菌(M.tb)的人和小鼠的联合研究提供了 支持氧化应激和相关炎症作为驱动因素的作用。因此，在我们的西班牙裔中 在人类队列中，我们发现系统性氧化应激在结核病或糖尿病患者中更高，并加剧了年龄效应。 我们假设，导致器官衰竭的与衰老相关的免疫代谢变化主要源于 线粒体驱动的氧化应激途径受损。我们将测试这些假设，进行快照 以及对人体的纵向研究。我们将确定这些变化开始的年龄和受影响最大的年龄 途径，侧重于从相对非侵入性标本中获得的单核细胞。也就是说，血。这些研究将 利用德克萨斯州-墨西哥边境定义明确的西班牙裔临床队列和我们成熟的团队 实地调查人员。在目标1中，我们将确定：i)何时改变线粒体诱导的氧化措施 在衰老过程中，首先在血液和单核细胞中检测到应激和免疫功能障碍，以确定 干预措施最有效的年龄。在目标2中，我们将确定宿主生物扰动的影响 (血糖异常和肺结核)对这些结果的影响。我们将进一步评估肺结核是否可以作为一种新的模式 加速衰老，因为它与炎症和氧化应激有关。总体而言，结果将提供 为未来临床测试选定的体内干预措施和监测个体化反应奠定基础 通过简单的生物标记物测试，促进延长细胞健康和器官系统健康跨度。

Old age is associated with a high prevalence of metabolic alterations like type 2 diabetes mellitus (DM) and preOM 0ointly 'dysglycemia'), and with an immunologic decline associated with higher risk of developing and dying from lung infections like pulmonary tuberculosis (PTB). These immune-metabolic alterations are accompanied by failure in other organ systems (lung, brain, skeletal muscle), leading to increased morbidity and mortality. Understanding these interactions and detecting them early is critical for delaying, preventing or restoring an individual's organ system health. The underlying mechanisms for immunometabolic alterations are unknown, but our joint studies in humans and mice with and without Mycobacterium tuberculosis (M.tb) infection provide support for the role of oxidative stress and associated inflammation as a driver. Accordingly, in our Hispanic human cohort, we find that systemic oxidative stress is higher in TB or DM patients, and exacerbates age effects. We hypothesize that aging-related immunometabolic changes that drive organ failure are largely originated from impaired mitochondria-driven oxidative stress pathways. We will test these hypotheses, conducting snap-shot and longitudinal studies in humans. We will identify the age at which these changes initiate and the most affected pathway, focusing on monocytes attained from relatively non-invasive specimens. i.e., blood. These studies will take advantage of a well-defined Hispanic clinical cohort at the Texas-Mexico border and our established team of field investigators. In Aim 1, we will determine: i) when altered measures of mitochondria-induced oxidative stress and immune dysfunction are first detected in blood and monocytes during the process of aging, to identify the most effective age for interventions. In Aim 2, we will determine the impact of host biological perturbations (dysglycemia and PTB) on these outcomes. We will further evaluate if PTB may serve as a new model of accelerated aging, given its association with inflammation and oxidative stress. Overall, results will provide the foundation for future clinical testing selected interventions in-vivo and monitoring individualized responsiveness with simple biomarker testing, to promote extended cellular health and organ system healthspan.