ArticleAging cell2015
The Achilles' heel of senescent cells: from transcriptome to senolytic drugs.
Article in Aging cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1,478 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
1,478 citing papers in PubMed, 2 syntheses or guidelines pooled it, 2,329 citations in OpenAlex.
- Senogenic-senolytic treatment strategies enhance tumor control and can improve survival in murine cancer models: a systematic review.BMC cancer · 2026Pooled it
- Targeting cellular senescence with Traditional Chinese Medicine: advances in neurodegenerative disorder treatment.Frontiers in neurology · 2026Pooled it
- Exploratory Effects of a Novel Nutraceutical on Senescence-Related Protein Biomarkers in Healthy Adults: A Pilot Proteomics Study.International journal of molecular sciences · 2026Trial
- Circulating Metabolites Treat Human TMJ-OA by Eliminating Senescent Chondrocytes via the C1QBP/C1q/p14ARF Axis.Journal of extracellular vesicles · 2026Trial
- Harnessing the NKG2D immune surveillance pathway using engineered T-cells for the treatment of human disease.Human vaccines & immunotherapeutics · 2026Review
- Stem cell senescence as a regenerative bottleneck in age-related skeletal degeneration: Mechanistic crosstalk and translational strategies.Regenerative therapy · 2026Review
- Hepatocyte senescence in metabolic dysfunction-associated steatotic liver disease (MASLD).Hepatology communications · 2026Review
- p53 wild-type/low c-Myc-expressing ONS76 pediatric medulloblastoma cells become senescent after gamma-irradiation and can be eliminated by senolytic substances.Cell death discovery · 2026Article
- Cellular senescence: six decades of discovery and reinvention.The EMBO journal · 2026Review
- Myelination and Remyelination in Peripheral Nerve Injury: Mechanisms, Regulation, and Therapeutic Perspectives.MedComm · 2026Review
- Future directions of osteoanabolic therapies in osteoporosis: Integrating current anabolic agents and emerging senescence-targeted strategies.Best practice & research. Clinical rheumatology · 2026Review
- A compendium of circulating biomarkers of senescence in humans: Insights on mechanistic impact across health domains and modulation by therapeutic interventions.Ageing research reviews · 2026Review
- Senolytics dasatinib and quercetin in metabolic dysfunction-associated steatohepatitis: a proof-of-principle randomized, controlled trial.Nature metabolism · 2026Article
- Chronic subdural hematoma through the hallmarks of aging: a geroscience framework for the commonest neurosurgical condition of older adults.GeroScience · 2026Review
- Renal Tubular Epithelial Cells Senescence Induced by 1-Aminopyrene Activates Fibroblast via BRD4 Driven Senescence-Associated Secretory Phenotype Signaling.Journal of biochemical and molecular toxicology · 2026Article
- Targeting cellular senescence in dermatology: senolytic and senomorphic strategies.GeroScience · 2026Review
- mRNA Therapeutics for Skin Rejuvenation: From Aging Atlases to Clinical Translation.Experimental dermatology · 2026Review
- Long-Term Human Skin Platform for Modeling Chronic Inflammation, Environmental Stress, and Therapeutic Intervention.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Cellular senescence and regulated cell death in cancer: mechanisms, cross-regulatory networks and therapeutic implications.Journal of hematology & oncology · 2026Review
- Therapy-Induced Senescence in Cancer Treatment Resistance: Mechanisms, Evidence, and Translational Opportunities.Cancers · 2026Review
1,418 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
33 authors at 6 institutions in 1 country.
Funding
Abstract
The healthspan of mice is enhanced by killing senescent cells using a transgenic suicide gene. Achieving the same using small molecules would have a tremendous impact on quality of life and the burden of age-related chronic diseases. Here, we describe the rationale for identification and validation of a new class of drugs termed senolytics, which selectively kill senescent cells. By transcript analysis, we discovered increased expression of pro-survival networks in senescent cells, consistent with their established resistance to apoptosis. Using siRNA to silence expression of key nodes of this network, including ephrins (EFNB1 or 3), PI3Kδ, p21, BCL-xL, or plasminogen-activated inhibitor-2, killed senescent cells, but not proliferating or quiescent, differentiated cells. Drugs targeting these same factors selectively killed senescent cells. Dasatinib eliminated senescent human fat cell progenitors, while quercetin was more effective against senescent human endothelial cells and mouse BM-MSCs. The combination of dasatinib and quercetin was effective in eliminating senescent MEFs. In vivo, this combination reduced senescent cell burden in chronologically aged, radiation-exposed, and progeroid Ercc1(-/Δ) mice. In old mice, cardiac function and carotid vascular reactivity were improved 5 days after a single dose. Following irradiation of one limb in mice, a single dose led to improved exercise capacity for at least 7 months following drug treatment. Periodic drug administration extended healthspan in Ercc1(-/∆) mice, delaying age-related symptoms and pathology, osteoporosis, and loss of intervertebral disk proteoglycans. These results demonstrate the feasibility of selectively ablating senescent cells and the efficacy of senolytics for alleviating symptoms of frailty and extending healthspan.
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What OpenQuestion holds
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.