The Regulation of Inflammatory Gene Responses in Aging

描述（由申请人提供）：本申请中提出的研究将确定血小板和单核细胞功能的年龄相关变化，这些变化促进了促炎环境，并有助于老年患者的发病率和死亡率。完成这些研究的多学科研究团队将联合具有老年学研究专业知识的资深研究人员和具有成功转化研究记录的初级研究人员。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的注册表，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，在老年人和年轻人中。我们还将描述在衰老过程中发生的从经典（CD14+/CD16-）到非经典，促炎单核细胞群体（CD14+/CD16+）的转变。我们的研究将确定改变的血小板-单核细胞相互作用是通过p选择素依赖还是独立的机制介导的。从这些研究中产生的数据将直接导致老年研究的新调查方法，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的炎症性和血栓性疾病提供新的治疗靶点的基础。

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.