Microglia, as macrophages in the brain, exhibit dysfunction with aging, such as impaired phagocytic capability and elevated neuroinflammation. However, the mechanisms underlying microglial aging remain unclear. The heterogeneity of microglia further challenges this context. Disrupted-in-schizophrenia 1 (DISC1), a psychiatric disorder susceptibility gene disrupted by translocation, plays an essential role in regulating the development and function of neurons. We observe that DISC1 is also expressed in microglia, where it exhibits an aggregates-like pattern (Figure A). We called this population of microglia as DISC1 aggregates positive microglia. We observe that both the proportion of DISC1 aggregates-positive microglia among total microglia and the size of DISC1 aggregates in microglia increase in the brain of aged mice (Figures B-C). DISC1 aggregates-positive microglia express senescent markers, e.g., lipofuscin and p16INK4A, which is exaggerated by amyloid-beta accumulation (Figures D-E). DISC1 aggregates-positive microglia display aging-like microglia phenotypes, such as enlarged cell bodies, reduced morphological branches, and impaired phagocytotic capability concomitant with a lysosomal dysfunction (Figures F-H). These results suggest that DISC1 plays an essential role in microglial aging.