Regulation of kidney function and blood pressure in aging

Project Summary The incidence of kidney dysfunction and hypertension increases with age. The prevalence of chronic kidney disease (CKD) and hypertension is higher in the aged than in the young population. Salt sensitivity is more prevalent in the elderly population. The aging-associated salt sensitivity is an important factor that contributes to the increased prevalence of hypertension in the elderly population. However, the underlying mechanism of aging-associated salt-sensitive hypertension is poorly understood. Exosomes are small bi-lipid membrane-bound vesicles that are produced in the endosomal compartment and released to extracellular spaces as intercellular messengers which regulate cell functions via a paracrine manner. The objective of the proposed research is to determine whether renal stem cell-derived exosomes (RSC-exosomes) play a role in the maintenance of normal kidney function and blood pressure and whether RSC-exosomes is involved in the pathogenesis of aging-associated kidney dysfunction, salt sensitivity and hypertension. This objective will be achieved by pursuing two interrelated specific aims using a combination of several novel technical approaches. The specific aims are: (1) Determine whether RSC-exosomes play a role in the regulation of renal function and blood pressure. (2) Investigate whether downregulation of RSC-exosomes contributes to aging-associated kidney dysfunction, salt sensitivity and hypertension. These studies will demonstrate, for the first time, an important role of RSC-exosomes in the regulation of kidney function and blood pressure and the pathogenesis of hypertension. The results will reveal novel mechanisms that RSC-exosomes may protect the kidney. Completion of the project may offer new insights into therapeutic strategies for aging-associated kidney dysfunction and hypertension and related cardiovascular disorder.