ArticleNature2016
Naturally occurring p16(Ink4a)-positive cells shorten healthy lifespan.
Article in Nature, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1,640 papers, 2 of them syntheses that pooled it.
What it found
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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.
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Who cites it
1,640 citing papers in PubMed, 2 syntheses or guidelines pooled it, 2,691 citations in OpenAlex.
- Targeting cellular senescence with Traditional Chinese Medicine: advances in neurodegenerative disorder treatment.Frontiers in neurology · 2026Pooled it
- Mapping the aging kidney: a bibliometric atlas of cellular senescence and future frontiers since the 20th century.Frontiers in nephrology · 2026Pooled it
- Safety and efficacy of allogeneic umbilical cord-derived mesenchymal stem cell infusion for frailty: a phase 2, single-centre, randomised, open-label controlled trial.EBioMedicine · 2026Trial
- Circulating Metabolites Treat Human TMJ-OA by Eliminating Senescent Chondrocytes via the C1QBP/C1q/p14ARF Axis.Journal of extracellular vesicles · 2026Trial
- 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
- Genomic, epigenomic and transcriptomic regulation of cellular senescence.Nature reviews. Genetics · 2026Review
- Caloric restriction attenuates age-related liver and kidney alterations in mice: Histological evidence.Histology and histopathology · 2026Article
- 4-Octyl Itaconate Attenuates Age-Induced Parotid Gland Dysfunction Through the Suppression of Fibrosis and Lipid Deposition by AMPKα/PPARα and the Inhibition of Oxidative Stress via the AMPKα/Nrf2 Signaling Pathway.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Back to youth: flipping the switch on tissue-resident macrophages.Signal transduction and targeted therapy · 2026Article
- Cellular senescence: six decades of discovery and reinvention.The EMBO journal · 2026Review
- Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.Signal transduction and targeted therapy · 2026Review
- Loss of Erbin in tubular epithelial cells sensitizes mice to acute kidney injury and aggravates renal fibrosis.The EMBO journal · 2026Article
- Methylation-associated Gene Expression (MaGE): a non-invasive, in vivo measure of cellular senescence.medRxiv : the preprint server for health sciences · 2026Article
- Chronic subdural hematoma through the hallmarks of aging: a geroscience framework for the commonest neurosurgical condition of older adults.GeroScience · 2026Review
- mRNA Therapeutics for Skin Rejuvenation: From Aging Atlases to Clinical Translation.Experimental dermatology · 2026Review
- Autologous cytokine-induced NK cells as candidate cellular senolytics: evidence, obstacles, and the experiments still needed.GeroScience · 2026Review
- The role of senescence in kidney ageing, injury and fibrosis.Nature reviews. Nephrology · 2026Review
- Cellular senescence and the SASP in skeletal ageing: convergent mechanisms of progressive bone loss in osteoporosis.Biogerontology · 2026Review
- Senescent Cell Heterogeneity: Tissue-Dependent Signatures and Age Dynamics Revealed by Human scRNA-Seq Data.International journal of molecular sciences · 2026Article
1,580 more citing papers are in PubMed but not listed here.
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13 authors at 1 institution in 1 country.
Funding
Abstract
Cellular senescence, a stress-induced irreversible growth arrest often characterized by expression of p16(Ink4a) (encoded by the Ink4a/Arf locus, also known as Cdkn2a) and a distinctive secretory phenotype, prevents the proliferation of preneoplastic cells and has beneficial roles in tissue remodelling during embryogenesis and wound healing. Senescent cells accumulate in various tissues and organs over time, and have been speculated to have a role in ageing. To explore the physiological relevance and consequences of naturally occurring senescent cells, here we use a previously established transgene, INK-ATTAC, to induce apoptosis in p16(Ink4a)-expressing cells of wild-type mice by injection of AP20187 twice a week starting at one year of age. We show that compared to vehicle alone, AP20187 treatment extended median lifespan in both male and female mice of two distinct genetic backgrounds. The clearance of p16(Ink4a)-positive cells delayed tumorigenesis and attenuated age-related deterioration of several organs without apparent side effects, including kidney, heart and fat, where clearance preserved the functionality of glomeruli, cardio-protective KATP channels and adipocytes, respectively. Thus, p16(Ink4a)-positive cells that accumulate during adulthood negatively influence lifespan and promote age-dependent changes in several organs, and their therapeutic removal may be an attractive approach to extend healthy lifespan.
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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.