Identification of lipid senolytics targeting senescent cells through ferroptosis induction

Through phenotypic drug screening, we identified a novel class of lipid senolytics that selectively eliminated a broad range of senescent cells, reduced tissue senescence, and extended healthspan in mice. Extensive mechanistic studies reveal that these lipids induce ferroptotic cell death by exploiting the iron-rich and ROS-prone characteristics of senescent cells, offering a new therapeutic strategy to target senescence in aging and age-related diseases. Overall design: Primary mouse embryonic fibroblasts (MEFs) cells were used. WT MEFs non-senescent (proliferative control) and WT MEFs induced to senescence by oxidative stress (H2O2) and genotoxic stress (etoposide). Cells were treated with a-ESA and its derivative a-ESA-me for 12 hours. 3 biological replicates per group.