ArticleAging2022
Synergism of BCL-2 family inhibitors facilitates selective elimination of senescent cells.
Article in Aging, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
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The trial behind it
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Who cites it
30 citing papers in PubMed, 40 citations in OpenAlex.
- Article
- In silico screening, synthesis, and biological evaluation of pyrazolopyrimidine-derived mTOR inhibitors for anticancer and senomorphic effects.Cancer cell international · 2026Article
- From Platelet Toxicity to Precision Targeting: Evolving Strategies to Overcome Thrombocytopenia in BCL-2/BCL-XL Inhibition.Health science reports · 2026Article
- PARP1 regulates the genomic ribonucleotide processing activity of TOP1 to prevent the formation of toxic TOP1-DNA adducts and the associated mutations.bioRxiv : the preprint server for biology · 2026Article
- Targeting cellular senescence in diabetic kidney disease: potential of regenerative, cell-based therapies and other senotherapeutic approaches.Kidney international · 2026Review
- Clearance of Senescent Cells by BCLAging cell · 2026Article
- Integrative Approaches to Treating Cellular Senescence in Kidney Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Homoharringtonine exhibits senotherapeutic activity that mitigates diet- and age-associated obesity and insulin resistance and extends lifespan in mice.Nature communications · 2026Article
- Disproportionality Analysis of Hematologic Adverse Event Signals Associated with Venetoclax in Combination with Senescence-Inducing Chemotherapy.Journal of clinical medicine · 2026Article
- UBE3A-mediated mH2A1 Ubiquitination activates TERT transcription to promote senescence resistance in pancreatic cancer.Cell death & disease · 2026Article
- Protodioscin enhances Methotrexate-induced senescence and senolytic activity in HepG2 liver cancer spheroids by modulating cell cycle regulators and the TGF-β/p-Smad2-4 signaling pathway.Scientific reports · 2025Article
- A Mendelian randomization-based risk model using aging-related genes for prognosis in lung adenocarcinoma.Discover oncology · 2025Article
- Targeting DNA damage in ageing: towards supercharging DNA repair.Nature reviews. Drug discovery · 2025Review
- Synephrine Inhibits Oxidative Stress and HCell biochemistry and biophysics · 2025Article
- Apoptotic priming in senescence predicts specific senolysis by quantitative analysis of mitochondrial dependencies.Cell death and differentiation · 2025Article
- Review
- Investigating the aging-modulatory mechanism of Rasayana Churna, an Ayurvedic herbal formulation, using a computational approach.Biogerontology · 2025Article
- Senolytic agent ABT-263 mitigates low- and high-LET radiation-induced gastrointestinal cancer development inAging · 2025Article
- Construction and validation of a senescence-related gene signature for early prediction and treatment of osteoarthritis based on bioinformatics analysis.Scientific reports · 2024Article
- Cellular senescence in metastatic prostate cancer: A therapeutic opportunity or challenge (Review).Molecular medicine reports · 2024Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Accumulation of senescent cells in tissues with advancing age participates in the pathogenesis of several human age-associated diseases. Specific senescent secretome, the resistance of senescent cells to apoptotic stimuli, and lack of immune system response contribute to the accumulation of senescent cells and their adverse effects in tissues. Inhibition of antiapoptotic machinery, augmented in senescent cells, by BCL-2 protein family inhibitors represents a promising approach to eliminate senescent cells from tissues. This study aimed to explore synergistic and selective senolytic effects of anti-apoptotic BCL-2 family targeting compounds, particularly BH3 mimetics. Using human non-transformed cells RPE-1, BJ, and MRC-5 brought to ionizing radiation-, oncogene-, drug-induced and replicative senescence, we found synergy in combining MCL-1 selective inhibitors with other BH3 mimetics. In an attempt to uncover the mechanism of such synergy, we revealed that the surviving subpopulation of cells resistant to individually applied ABT-737/ABT-263, MIK665, ABT-199, and S63845 BCL-2 family inhibitors showed elevated MCL-1 compared to untreated control cells indicating the presence of a subset of cells expressing high MCL-1 levels and, therefore, resistant to BCL-2 inhibitors within the original population of senescent cells. Overall, we found that combining BCL-2 inhibitors can be beneficial for eliminating senescent cells, thereby enabling use of lower, potentially less toxic, doses of drugs compared to monotherapy, thereby overcoming the resistance of the subpopulation of senescent cells to monotherapy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.