The Regulation of Inflammatory Gene Responses in Aging

衰老过程中炎症基因反应的调节

• 批准号: 8183844
• 负责人: Matthew Thomas Rondina
• 金额: $ 7.48万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-15 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8183844
• 关键词: Acute; Age; Aging; Aging-Related Process; Atherosclerosis; Binding; Blood Platelets; CD14 gene; Cells; Complex; Data; Development; Disease; Elderly; Enrollment; FCGR3B gene; Genes; Immune system; Inflammation Mediators; Inflammatory; Inflammatory Response; Institutional Review Boards; Interleukin-6; Interleukin-8; Investigation; Knowledge; Lead; Mediating; Monocyte Chemoattractant Protein-1; Morbidity - disease rate; P-Selectin; P-selectin ligand protein; Platelet Activation; Platelet Count measurement; Population; Prevention; Prevention approach; Production; Proteins; Registries; Regulation; Research; Research Personnel; Risk; Risk Factors; Sampling; Sepsis; Testing; Thromboembolism; Translational Research; age related; aging population; base; cytokine; information gathering; monocyte; mortality; new therapeutic target; novel therapeutic intervention; older patient; response

DESCRIPTION (provided by applicant): The research proposed in this application will identify age-related changes in platelet and monocyte functions that promote a pro-inflammatory milieu and contribute to morbidity and mortality in elderly patients. The multi-disciplinary research team that will complete these studies unites established senior investigators with expertise in gerontological studies with junior investigators who have a proven track record of successful translational research. In addition, we have already received IRB approval for these studies and have established a registry of eligible young and elderly subjects allowing us to quickly enroll subjects and perform the proposed studies. We will study changes in platelet-monocyte interactions and the regulation of gene product synthesis, including IL-6 and MCP-1, in elderly and young subjects. We will also characterize shifts from a classical (CD14+/CD16-) to a non-classical, pro-inflammatory monocyte population (CD14+/CD16+) that occur during the aging process. Our investigations will identify whether altered platelet-monocyte interactions are mediated through P-selectin dependent, or independent, mechanisms. The data generated from these studies will lead directly to new investigative approaches in geriatric research and will fill important knowledge gaps. Ultimately, this information will provide the basis for novel therapeutic targets for the prevention and treatment of inflammatory and thrombotic disorders in elderly patients. PUBLIC HEALTH RELEVANCE: Aging is associated with significant increases in the risk of inflammatory and thrombotic disorders. The research proposed in this application will identify how the functions of platelets and monocytes are altered in elderly subjects and how these changes lead to the synthesis of pro-inflammatory gene products. The information gathered from these studies will help us understand how inflammatory responses are regulated in elderly subjects and how to develop new treatments for an aging population.

描述（由申请人提供）：本申请中提出的研究将确定与年龄相关的血小板和单核细胞功能的变化，这些变化促进了促炎的环境，并有助于老年患者的发病率和死亡率。将完成这些研究的多学科研究团队将知名的高级研究人员与具有成功转化研究的良好记录的初级研究人员一起在老年学研究领域具有专业知识。此外，我们已经获得了IRB批准这些研究，并建立了合格的年轻和老年受试者的注册表，使我们能够快速入学受试者并进行拟议的研究。 我们将研究老年人和年轻受试者中血小板 - 单细胞相互作用的变化以及基因产物合成（包括IL-6和MCP-1）的调节。我们还将表征从经典的（CD14+/CD16-）转变为在老化过程中发生的非经典的，促炎性单核细胞种群（CD14+/CD16+）。我们的研究将确定是否通过依赖性或独立的机制来介导的血小板 - 单细胞相互作用改变是介导的。 这些研究产生的数据将直接导致老年研究中的新调查方法，并填补重要的知识差距。最终，这些信息将为老年患者预防和治疗炎症和血栓性疾病的新型治疗靶点提供基础。 公共卫生相关性：衰老与炎症和血栓性疾病的风险显着增加有关。本应用程序中提出的研究将确定老年受试者中血小板和单核细胞的功能如何改变，以及这些变化如何导致促炎基因产物的综合。从这些研究中收集的信息将有助于我们了解如何在老年受试者中调节炎症反应以及如何为老年人群开发新的治疗方法。