Senescent microglia play a critical role in brain aging and neurodegenerative diseases. As microglia, the brain's resident immune cells, age, they become senescent, leading to chronic inflammation and impaired function. This process contributes to the progression of neurodegenerative diseases such as Alzheimer's, Parkinson's, and amyotrophic lateral sclerosis (ALS). Senescent microglia exhibit a senescence-associated secretory phenotype (SASP), releasing inflammatory molecules that promote further aging and disease. The accumulation of senescent microglia in the brain is linked to the threshold theory of senescent cell accumulation, where a critical number of senescent cells can trigger aging-related diseases. Senescent microglia are increasingly recognized as a promising therapeutic target for neurodegenerative diseases. They contribute to the pathogenesis of these conditions through their altered immune functions and interactions with other brain cells. Recent studies suggest that senescent microglia may be particularly vulnerable to aging and senescence-inducing factors such as DNA damage, oxidative stress, and protein aggregates. The unique origin and characteristics of yolk sac-derived microglia, which have a limited capacity for repopulation, suggest an intrinsic connection to their senescence and potential contribution to neurodegenerative diseases. The accumulation of senescent microglia, along with their altered immune functions, may play a critical role in the pathogenesis of neurodegenerative conditions. Recent findings indicate that microglia are a major contributor to brain aging, as determined by bulk-seq common aging score calculations. The threshold theory of senescent cell accumulation suggests that when the number of senescent cells in the body surpasses a threshold, the immune system and other organs become more prone to aging-related diseases. Senescent microglia can also contribute to the propagation of brain aging through paracrine signaling, leading to the aging of the entire brain. Senescent microglia are also associated with neuroinflammatory responses and the accumulation of pathological proteins such as tau and amyloid-beta. The TREM2-APOE pathway plays a crucial role in microglial function and phenotype in neurodegenerative diseases. The accumulation of lipid droplets and protein aggregates in senescent microglia can lead to impaired phagocytic function and metabolic dysfunction, contributing to the progression of neurodegenerative diseases. Recent studies have explored the potential of senolytics, compounds that target and eliminate senescent cells, as a therapeutic approach for neurodegenerative diseases. Senolytic treatment has shown promise in reducing senescent cells and attenuating inflammation in animal models of neurodegenerative diseases. Additionally, strategies such as metabolic reprogramming, autophagy restoration, and the use of recombinant TREM2-activating antibodies are being investigated as potential approaches for microglial rejuvenation. In conclusion, senescentSenescent microglia play a critical role in brain aging and neurodegenerative diseases. As microglia, the brain's resident immune cells, age, they become senescent, leading to chronic inflammation and impaired function. This process contributes to the progression of neurodegenerative diseases such as Alzheimer's, Parkinson's, and amyotrophic lateral sclerosis (ALS). Senescent microglia exhibit a senescence-associated secretory phenotype (SASP), releasing inflammatory molecules that promote further aging and disease. The accumulation of senescent microglia in the brain is linked to the threshold theory of senescent cell accumulation, where a critical number of senescent cells can trigger aging-related diseases. Senescent microglia are increasingly recognized as a promising therapeutic target for neurodegenerative diseases. They contribute to the pathogenesis of these conditions through their altered immune functions and interactions with other brain cells. Recent studies suggest that senescent microglia may be particularly vulnerable to aging and senescence-inducing factors such as DNA damage, oxidative stress, and protein aggregates. The unique origin and characteristics of yolk sac-derived microglia, which have a limited capacity for repopulation, suggest an intrinsic connection to their senescence and potential contribution to neurodegenerative diseases. The accumulation of senescent microglia, along with their altered immune functions, may play a critical role in the pathogenesis of neurodegenerative conditions. Recent findings indicate that microglia are a major contributor to brain aging, as determined by bulk-seq common aging score calculations. The threshold theory of senescent cell accumulation suggests that when the number of senescent cells in the body surpasses a threshold, the immune system and other organs become more prone to aging-related diseases. Senescent microglia can also contribute to the propagation of brain aging through paracrine signaling, leading to the aging of the entire brain. Senescent microglia are also associated with neuroinflammatory responses and the accumulation of pathological proteins such as tau and amyloid-beta. The TREM2-APOE pathway plays a crucial role in microglial function and phenotype in neurodegenerative diseases. The accumulation of lipid droplets and protein aggregates in senescent microglia can lead to impaired phagocytic function and metabolic dysfunction, contributing to the progression of neurodegenerative diseases. Recent studies have explored the potential of senolytics, compounds that target and eliminate senescent cells, as a therapeutic approach for neurodegenerative diseases. Senolytic treatment has shown promise in reducing senescent cells and attenuating inflammation in animal models of neurodegenerative diseases. Additionally, strategies such as metabolic reprogramming, autophagy restoration, and the use of recombinant TREM2-activating antibodies are being investigated as potential approaches for microglial rejuvenation. In conclusion, senescent