ArticleNature medicine2016
Clearance of senescent cells by ABT263 rejuvenates aged hematopoietic stem cells in mice.
Article in Nature medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1,081 papers, 1 of them a synthesis that pooled it.
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Who cites it
1,081 citing papers in PubMed, 1 synthesis or guideline pooled it, 1,719 citations in OpenAlex.
- Advances in the Regulation of Hematopoietic Homeostasis by Programmed Cell Death Under Radiation Conditions.Stem cell reviews and reports · 2025Pooled it
- Immunotherapy and senolytics in head and neck squamous cell carcinoma: phase 2 trial results.Nature medicine · 2025Trial
- Stem cell senescence as a regenerative bottleneck in age-related skeletal degeneration: Mechanistic crosstalk and translational strategies.Regenerative therapy · 2026Review
- Intracranial aneurysms as a manifestation of premature vascular aging: Cellular senescence, inflammaging, and wall degeneration.Ageing research reviews · 2026Review
- Senotherapeutic potential against xeroderma pigmentosum.Stem cell research & therapy · 2026Article
- Orthogonal Light- and Enzyme-Triggered and-Gate Prodrugs for Senolytic Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Cellular senescence: six decades of discovery and reinvention.The EMBO journal · 2026Review
- Mechanisms of Hematopoietic Stem Cell Aging and Emerging Rejuvenation Strategies.Stem cell reviews and reports · 2026Review
- Targeting cellular senescence in dermatology: senolytic and senomorphic strategies.GeroScience · 2026Review
- BCLXSignal transduction and targeted therapy · 2026Article
- Chronic Radiation-Induced Wounds: Pathogenesis, Current Therapeutic Strategies, and Emerging Regenerative Approaches.International journal of molecular sciences · 2026Review
- The vicious cycle of SASP and inflammaging promotes aging and age-related diseases.Communications biology · 2026Review
- HIF1AJournal for immunotherapy of cancer · 2026Article
- Closing the gap in aging science: unlocking the potential of nanoparticles in senescence therapy.Biogerontology · 2026Review
- Timing-Dependent Clearance of p16-Positive Cells Mitigates Radiation-Induced Accelerated Aging.Aging cell · 2026Article
- Obesity accelerates aging: Mechanisms and therapeutic implications.Genes & diseases · 2026Review
- Review
- Fibrillarin Resists Cellular Senescence Via SIRT1-Dependent Nicotinamide Metabolism and Its Inhibition Sensitizes Senolytic Therapy in Esophageal Squamous Cell Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Pathological Mechanism-Inspired Biomimetic Nano-Senotherapy for Reversing Experimental Atherosclerosis in ApoEAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Targeted clearance of senescent cells alleviates alcohol-associated liver disease by restoring cellular function and immune balance.GeroScience · 2026Article
1,021 more citing papers are in PubMed but not listed here.
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Authors and funding
18 authors at 6 institutions in 2 countries.
Funding
Abstract
Senescent cells (SCs) accumulate with age and after genotoxic stress, such as total-body irradiation (TBI). Clearance of SCs in a progeroid mouse model using a transgenic approach delays several age-associated disorders, suggesting that SCs play a causative role in certain age-related pathologies. Thus, a 'senolytic' pharmacological agent that can selectively kill SCs holds promise for rejuvenating tissue stem cells and extending health span. To test this idea, we screened a collection of compounds and identified ABT263 (a specific inhibitor of the anti-apoptotic proteins BCL-2 and BCL-xL) as a potent senolytic drug. We show that ABT263 selectively kills SCs in culture in a cell type- and species-independent manner by inducing apoptosis. Oral administration of ABT263 to either sublethally irradiated or normally aged mice effectively depleted SCs, including senescent bone marrow hematopoietic stem cells (HSCs) and senescent muscle stem cells (MuSCs). Notably, this depletion mitigated TBI-induced premature aging of the hematopoietic system and rejuvenated the aged HSCs and MuSCs in normally aged mice. Our results demonstrate that selective clearance of SCs by a pharmacological agent is beneficial in part through its rejuvenation of aged tissue stem cells. Thus, senolytic drugs may represent a new class of radiation mitigators and anti-aging agents.
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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.