Characteristics of senescent cells resistant to ABT263 and ARV825

ABT263 and ARV825 were identified as promising senolytic drugs based on our criteria. However, 20–30% of senescent cells survived treatment with these agents. To clarify why a subset of senescent cells remained resistant, we performed RNA-seq to characterize the surviving population. Several SASP factors were upregulated compared with untreated senescent cells, suggesting that incomplete senolysis may diminish therapeutic benefits and that more effective elimination of senescent cells is required. In addition, AKR1C1–3, which are involved in detoxifying reactive carbonyl species and reducing oxidative stress, were also upregulated. These results suggest that the surviving cells may overcome mitochondrial stress by preserving mitochondrial membrane potential and limiting ROS accumulation. Overall design: RNA-seq profiling of doxorubicin-induced senescent TIG-3 cells with ABT263, ARV825, or vehicle (DMSO) for 7days.