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）：本申请中拟定的研究将确定血小板和单核细胞功能的年龄相关变化，这些变化促进促炎环境并导致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具有老年学研究专业知识的资深研究人员与具有成功转化研究记录的初级研究人员联合起来。此外，我们已经获得了IRB对这些研究的批准，并建立了符合条件的年轻和老年受试者登记，使我们能够快速招募受试者并进行拟议的研究。 我们将研究老年和年轻受试者血小板-单核细胞相互作用的变化和基因产物合成的调节，包括IL-6和MCP-1。我们还将描述在衰老过程中发生的从经典（CD 14 +/CD 16-）到非经典促炎单核细胞群（CD 14 +/CD 16+）的变化。我们的研究将确定血小板-单核细胞相互作用的改变是否是通过P-选择素依赖性或独立机制介导的。 这些研究产生的数据将直接导致老年医学研究的新的调查方法，并将填补重要的知识空白。最终，这些信息将为预防和治疗老年患者炎症和血栓性疾病的新治疗靶点提供基础。 公共卫生相关性：衰老与炎症和血栓性疾病风险的显著增加相关。本申请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合成。从这些研究中收集的信息将帮助我们了解老年受试者的炎症反应是如何调节的，以及如何为老龄化人群开发新的治疗方法。