Project Summary The goal of this proposal is to understand how aging and senescent cells impact resident memory T cell differentiation, longevity, and functional interactions with individual tissue cell types, including parenchymal, stromal, innate and adaptive immune cells. Single cell assays will address gaps in understanding of resident memory T cell dialogue with resident hematopoietic and non-hematopoietic cells in both mouse and humans. The impact of the age of the organism, the age of the T cell, or targeted elimination of senescent cell populations will be tested as isolated variables. This study will inform mechanisms of immune disfunction in the elderly and therapeutic opportunities for rejuvenating tissue immunity.