The process of aging represents the gradual deterioration of function with time, which affects almost all tissues and organs. In humans, it is the most prevailing risk factor for the morbidity and mortality attributable to numerous acute and chronic diseases. However, the cellular and molecular bases for these phenomena remain largely unknown. Our preliminary work has uncovered a striking build-up of tissue macrophages that carry numerous markers of senescence in multiple organs of aged mice, implicating loss or alteration of macrophage function as a potential driver of aging phenotype including inflammaging. In this project, we will uncover the mechanisms underlying age- and inflammation-induced senescence/senescence-like state of tissue macrophages, we will determine how this shapes tissue inflammation and immune response during aging, and we will explore how modulation of macrophage senescence could be used to impact the aging process.