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Heterogeneity of senescent cells underlies resistance to ABT263 and ARV825

GSE313494 Homo sapiens Expression profiling by high throughput sequencing 4 samples Submitted 2025/12/15 Platform GPL34284
Summary
ABT263 and ARV825 emerged as promising senolytic candidates based on our criteria. Nevertheless, 20–30% of senescent cells persisted after treatment with these compounds. To investigate why a subset of cells remained refractory, we examined scRNA-seq to profile the surviving population. Notably, several genes encoding V-ATPase subunits—such as ATP6V0E1, which are essential for lysosomal degradation of damaged organella—were consistently enriched in both ABT263- and ARV825-resistant senescent cells. These findings indicate that cells exhibiting elevated V-ATPase activity may evade senolytic action by more efficiently clearing damaged organelles, including mitochondria.
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 PRJNA1379648 and SRA study SRP654543. Searching any of these in the dataset finder brings you back here.

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