ArticleCell cycle (Georgetown, Tex.)2008
The yin and yang of the Cdkn2a locus in senescence and aging.
Article in Cell cycle (Georgetown, Tex.), 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis 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
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
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- Genetically Defined Organoid Models Reveal Mechanisms Driving Squamous Cell Neoplastic Evolution and Identify Potential Therapeutic Vulnerabilities.bioRxiv : the preprint server for biology · 2025Article
- CDKN2A and matrix metalloproteinases: key regulators of cellular senescence in squamous cell carcinoma.American journal of translational research · 2025Article
- DNA methylation correlates of chronological age in diverse human tissue types.Epigenetics & chromatin · 2024Article
- A Brain Anti-Senescence Transcriptional Program Triggered by Hypothalamic-Derived Exosomal microRNAs.International journal of molecular sciences · 2024Article
- Fusobacterium nucleatum triggers senescence phenotype in gingival epithelial cells.Molecular oral microbiology · 2024Article
- Heterogenous Differences in Cellular Senescent Phenotypes in Pre-Eclampsia and IUGR following Quantitative Assessment of Multiple Biomarkers of Senescence.International journal of molecular sciences · 2023Article
- TLR9 Mediates Periodontal Aging by Fostering Senescence and Inflammaging.Journal of dental research · 2022Article
- Morphological and transcriptional evaluation of multiple facial cutaneous hyperpigmented spots.Skin health and disease · 2022Article
- Genes and Longevity of Lifespan.International journal of molecular sciences · 2022Review
- Aneuploidy as a promoter and suppressor of malignant growth.Nature reviews. Cancer · 2021Review
- Cellular senescence in ageing: from mechanisms to therapeutic opportunities.Nature reviews. Molecular cell biology · 2021Review
- Oxidative Stress and Gene Expression Modifications Mediated by Extracellular Vesicles: An In Vivo Study of the Radiation-Induced Bystander Effect.Antioxidants (Basel, Switzerland) · 2021Article
- Epigenetics of Aging and Aging-Associated Diseases.International journal of molecular sciences · 2021Review
- Novel Insights into the Role of UBE3A in Regulating Apoptosis and Proliferation.Journal of clinical medicine · 2020Article
- The Interaction of Aging and Cellular Stress Contributes to Pathogenesis in Mouse and Human Huntington Disease Neurons.Frontiers in aging neuroscience · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Senescence of cultured cells involves activation of the p19(Arf)-p53 and the p16(Ink4a)-Rb tumor suppressor pathways. This, together with the observation that p19(Arf) and p16(Ink4a) expression increases with age in many tissues of humans and rodents, led to the speculation that these pathways drive in vivo senescence and natural aging. However, it has been difficult to test this hypothesis using a mammalian model system because inactivation of either of these pathways results in early death from tumors. One approach to bypass this problem would be to inactivate these pathways in a murine segmental progeria model such as mice that express low amounts of the mitotic checkpoint protein BubR1 (BubR1 hypomorphic mice). These mice have a five-fold reduced lifespan and develop a variety of early-aging associated phenotypes including cachetic dwarfism, skeletal muscle degeneration, cataracts, arterial stiffening, (subcutaneous) fat loss, reduced stress tolerance and impaired wound healing. Importantly, BubR1 hypomorphism elevates both p16(Ink4a) and p19(Arf) expression in skeletal muscle and fat. Inactivation of p16(Ink4a) in BubR1 mutant mice delays both cellular senescence and aging specifically in these tissues. Surprisingly, however, inactivation of p19(Arf) has the opposite effect; it exacerbates in vivo senescence and aging in skeletal muscle and fat. These mouse studies suggest that p16(Ink4a) is indeed an effector of aging and in vivo senescence, but p19(Arf) an attenuator. Thus, the role of the p19(Arf)-p53 pathway in aging and in vivo senescence seems far more complex than previously anticipated.
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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.