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Characteristics of senescent cells resistant to ABT263 and ARV825

GSE313462 Homo sapiens Expression profiling by high throughput sequencing 6 samples Submitted 2025/12/15 Platform GPL24676
Summary
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.
Published in
Comparative analysis of senolytic drugs reveals mitochondrial determinants of efficacy and resistance
Wakita M, Ito K, Fujii K et al. · Nature aging 2026 · PMID 41611832 · doi:10.1038/s43587-025-01057-z
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Also filed as BioProject PRJNA1379586 and SRA study SRP654452. Searching any of these in the dataset finder brings you back here.

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