Aging is a significant risk factor for the development of neurodegenerative disease like Alzheimer’s disease (AD) and Parkinson’s disease. Microglia, as important immune cells in the brain, play a crucial role in maintaining brain homeostasis, particularly related to iron storage and metabolism. Investigating the role of microglia in aging can provide insights into disease identification and potential therapies. Despite being long-lived immune cells, microglia have been understudied in the context of aging. Their heterogeneity and functions have not been fully explored, which is important given the emergence of therapies targeting microglia.The study aims to fill this knowledge gap by investigating the genetic profiles and functions of microglia from aged mice. This is done using RNA sequencing data to identify genes and pathways associated with aging and neurodegeneration. Functional characterization of microglia was performed by assessing activities like phagocytosis, cytokine production, oxidative stress response, and interactions with other brain cells.The study confirmed altered activities of microglial subpopulations, including senescent microglia. These cells showed deficits in phagocytosis, lipid metabolism, and immune responses. Histological examination also revealed an increase in hyperactivated as well as senescent microglia in both aged mice and AD mouse models.This suggests a potential link between microglial senescence and neurodegeneration in AD. This study has the potential to advance our understanding of the role of microglia in aging-related neurodegeneration and could contribute to the development of therapeutic strategies.