This study investigates the efficacy of NKG2D chimeric antigen receptor (CAR) engineered T cells in targeting and eliminating stress-induced senescent cells in vitro. Cellular senescence contributes to age-related tissue decline and is characterized by permanent cell cycle arrest and the senescence-associated secretory phenotype (SASP). Immunotherapy, particularly CAR-T cell therapy, emerges as a promising approach to selectively eliminate senescent cells. The focus is on the NKG2D receptor, which binds to ligands (NKG2DLs) upregulated in senescent cells, offering a target for CAR-T cells. Using mouse embryonic fibroblasts (MEFs) and astrocytes (AST) as senescence models, the study demonstrates elevated expression of NKG2DLs in response to genotoxic and oxidative stress. NKG2D-CAR T cells displayed potent cytotoxicity against these senescent cells, with minimal effects on non-senescent cells, suggesting their potential as targeted senolytics. The findings indicate that NKG2D-CAR T cells can target senescent brain cells, offering a novel approach to manage senescence-associated diseases. The study presents the first evidence of NKG2D-CAR T cells' ability to target senescent brain cells, suggesting their potential for future therapeutic applications in naturally aged organisms and models of aging-associated brain diseases. The study also highlights the potential of NKG2D-CAR T cells in targeting senescent cells induced by DNA damage and oxidative stress, with significant cytotoxic effects against these cells. The results suggest that NKG2D-CAR T cells could serve as potent senolytics for aging and age-related diseases. The study provides preliminary preclinical evidence of the efficacy of NKG2D-CAR T cells in eliminating stress-induced senescent cells in vitro. The findings suggest a broad clinical therapeutic potential of senolytic CAR-T cells. The study also highlights the importance of NKG2D ligands in the targeting of senescent cells and their potential as therapeutic targets. The study demonstrates the effectiveness of NKG2D-CAR T cells in targeting and eliminating senescent cells, with minimal off-target effects. The results suggest that NKG2D-CAR T cells could be a promising approach for the treatment of age-related diseases. The study also highlights the potential of NKG2D-CAR T cells in targeting senescent cells in the brain, indicating their targetability for senolytic therapy. The study provides a comprehensive understanding of the mechanisms and potential applications of NKG2D-CAR T cells in targeting senescent cells. The findings suggest that NKG2D-CAR T cells could be a promising approach for the treatment of age-related diseases. The study also highlights the importance of NKG2D ligands in the targeting of senescent cells and their potential as therapeutic targets. The studyThis study investigates the efficacy of NKG2D chimeric antigen receptor (CAR) engineered T cells in targeting and eliminating stress-induced senescent cells in vitro. Cellular senescence contributes to age-related tissue decline and is characterized by permanent cell cycle arrest and the senescence-associated secretory phenotype (SASP). Immunotherapy, particularly CAR-T cell therapy, emerges as a promising approach to selectively eliminate senescent cells. The focus is on the NKG2D receptor, which binds to ligands (NKG2DLs) upregulated in senescent cells, offering a target for CAR-T cells. Using mouse embryonic fibroblasts (MEFs) and astrocytes (AST) as senescence models, the study demonstrates elevated expression of NKG2DLs in response to genotoxic and oxidative stress. NKG2D-CAR T cells displayed potent cytotoxicity against these senescent cells, with minimal effects on non-senescent cells, suggesting their potential as targeted senolytics. The findings indicate that NKG2D-CAR T cells can target senescent brain cells, offering a novel approach to manage senescence-associated diseases. The study presents the first evidence of NKG2D-CAR T cells' ability to target senescent brain cells, suggesting their potential for future therapeutic applications in naturally aged organisms and models of aging-associated brain diseases. The study also highlights the potential of NKG2D-CAR T cells in targeting senescent cells induced by DNA damage and oxidative stress, with significant cytotoxic effects against these cells. The results suggest that NKG2D-CAR T cells could serve as potent senolytics for aging and age-related diseases. The study provides preliminary preclinical evidence of the efficacy of NKG2D-CAR T cells in eliminating stress-induced senescent cells in vitro. The findings suggest a broad clinical therapeutic potential of senolytic CAR-T cells. The study also highlights the importance of NKG2D ligands in the targeting of senescent cells and their potential as therapeutic targets. The study demonstrates the effectiveness of NKG2D-CAR T cells in targeting and eliminating senescent cells, with minimal off-target effects. The results suggest that NKG2D-CAR T cells could be a promising approach for the treatment of age-related diseases. The study also highlights the potential of NKG2D-CAR T cells in targeting senescent cells in the brain, indicating their targetability for senolytic therapy. The study provides a comprehensive understanding of the mechanisms and potential applications of NKG2D-CAR T cells in targeting senescent cells. The findings suggest that NKG2D-CAR T cells could be a promising approach for the treatment of age-related diseases. The study also highlights the importance of NKG2D ligands in the targeting of senescent cells and their potential as therapeutic targets. The study