The Regulation of Inflammatory Gene Responses in Aging

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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.