Senescence-targeted engineered CAR-T immunotherapy: advances, challenges and perspectives for engineered senolytic immunotherapy

Cellular senescence acts as a core driver of chronic diseases and tissue degeneration. Conventional small-molecule senolytics face critical limitations including poor target specificity and off-target toxicity when eliminating heterogeneous senescent cell populations. This review systematically discusses senescence-targeted engineered chimeric antigen receptor (CAR)-T immunotherapy, which achieves targeted clearance of pathological senescent cells by recognising specific surface markers. It summarises target-antigen evaluation frameworks, analyzes aged immunosuppressive microenvironment barriers and corresponding engineering strategies, and outlines composite efficacy assessment systems and tiered biomarker-monitoring workflows. Key translational bottlenecks such as imperfect antigen specificity and immune escape are also addressed. Preclinical studies verify organ function restoration and healthspan extension, while clinical evidence remains limited. Future integration of CAR-T technology with smart nanocarriers, synthetic biology and artificial intelligence will promote its clinical translation for senescence-associated disorders.