Yang, Jn-Simon, He et al. report that the dual BCL-xL/BCL-2 PROTAC 753b is a potent and liver-tropic senolytic, which (unlike other inhibitors of BCL-xL) does not cause severe thrombocytopenia. They evaluate its efficacy in natural aging and in reducing progression from steatotic liver disease to hepatocellular carcinoma, using mouse models.