In the central nervous system (CNS), microglia are resident immune cells and play an important role in maintaining homeostasis via inflammatory regulation and engulfment of cell debris or beta-amyloid. Thus, functional abnormalities in microglia are involved in the onset and progression of various CNS diseases. Recently, it has been reported that cellular senescence in microglia progresses more remarkably with aging than in other cells in the brain. In addition, senescent cells present senescent-associated secretory phenotype (SASP) which secretes inflammatory cytokines and chemokines. Therefore, the progression of cellular senescence in microglia might be a key factor in the pathogenesis of age-related neurodegenerative diseases. However, in vitro systems, primary cultured microglia isolated from rodent embryos or neonates have generally been used, but the details of age-related changes in microglial function have not been adequately analyzed in these cell systems. In this symposium, I will introduce our recently established model system of cellular senescence microglia and discuss the possibility that microglial dysfunction by cellular senescence is a potential drug target for age-related neurodegenerative diseases.