The study investigates the role of senescent cells in tau-dependent neurodegenerative diseases, specifically in a mouse model of tauopathy (MAPT P301S PS19). Senescent cells, characterized by irreversible cell-cycle arrest and a secretory phenotype, are known to contribute to tissue deterioration and aging-related diseases. The researchers found that senescent astrocytes and microglia accumulate in the brains of PS19 mice, leading to gliosis, hyperphosphorylation of tau protein, and neurodegeneration. Cleaving these senescent cells using the INK-ATTAC transgenic mice prevented these pathological changes and preserved cognitive function. Additionally, pharmacological intervention with a senolytic agent, ABT263, also reduced tau phosphorylation and improved cognitive performance. These findings suggest that targeting senescent cells may be a therapeutic approach to treat tau-mediated diseases.The study investigates the role of senescent cells in tau-dependent neurodegenerative diseases, specifically in a mouse model of tauopathy (MAPT P301S PS19). Senescent cells, characterized by irreversible cell-cycle arrest and a secretory phenotype, are known to contribute to tissue deterioration and aging-related diseases. The researchers found that senescent astrocytes and microglia accumulate in the brains of PS19 mice, leading to gliosis, hyperphosphorylation of tau protein, and neurodegeneration. Cleaving these senescent cells using the INK-ATTAC transgenic mice prevented these pathological changes and preserved cognitive function. Additionally, pharmacological intervention with a senolytic agent, ABT263, also reduced tau phosphorylation and improved cognitive performance. These findings suggest that targeting senescent cells may be a therapeutic approach to treat tau-mediated diseases.