ArticleAging cell2015
Reversible cell cycle inhibition and premature aging features imposed by conditional expression of p16Ink4a.
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 28 papers.
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.
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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
28 citing papers in PubMed, 45 citations in OpenAlex.
- Reduced stem cell aging in exercised human skeletal muscle is enhanced by ginsenoside Rg1.Aging · 2021Trial
- Molecular mechanisms and recent advances in cellular senescence.Cell & bioscience · 2026Review
- Cerebrovascular p16Acta neuropathologica communications · 2025Article
- Active chromatin marks and up-regulation of FOXC1 in uterine epithelial cells demarcate the onset of reproductive decline in aging females.NAR molecular medicine · 2025Article
- Cellular senescence and neurodegeneration.Human genetics · 2023Review
- Comparison of the effects of oxidative and inflammatory stresses on rat chondrocyte senescence.Scientific reports · 2023Article
- The Senescence Markers p16INK4A, p14ARF/p19ARF, and p21 in Organ Development and Homeostasis.Cells · 2022Review
- MiR-1-3p and MiR-124-3p Synergistically Damage the Intestinal Barrier in the Ageing Colon.Journal of Crohn's & colitis · 2022Article
- What programs the size of animal cells?Frontiers in cell and developmental biology · 2022Review
- Long-Term Social Isolation-Induced Autophagy Inhibition and Cell Senescence Aggravate Cognitive Impairment in D(+)Galactose-Treated Male Mice.Frontiers in aging neuroscience · 2022Article
- Deletion of p16 accelerates fracture healing in geriatric mice.American journal of translational research · 2021Article
- Cord blood serum harvesting by hydroxyethyl starch: a fetal bovine serum alternative in expansion of umbilical cord-derived mesenchymal stem cells.Cytotechnology · 2020Article
- Chronic expression of p16Nature communications · 2020Article
- Common and different alterations of bone marrow mesenchymal stromal cells in myelodysplastic syndrome and multiple myeloma.Cell proliferation · 2020Article
- Article
- p16Matrix biology : journal of the International Society for Matrix Biology · 2019Article
- The transcription factor Slug represses p16Nature communications · 2019Article
- Senescent Kidney Cells in Hypertensive Patients Release Urinary Extracellular Vesicles.Journal of the American Heart Association · 2019Article
- p53 induces senescence through Lamin A/C stabilization-mediated nuclear deformation.Cell death & disease · 2019Article
- Sirt6 overexpression suppresses senescence and apoptosis of nucleus pulposus cells by inducing autophagy in a model of intervertebral disc degeneration.Cell death & disease · 2018Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The cyclin-dependent kinase (Cdk) inhibitor p16(Ink4a) (p16) is a canonical mediator of cellular senescence and accumulates in aging tissues, where it constrains proliferation of some progenitor cells. However, whether p16 induction in tissues is sufficient to inhibit cell proliferation, mediate senescence, and/or impose aging features has remained unclear. To address these issues, we generated transgenic mice that permit conditional p16 expression. Broad induction at weaning inhibited proliferation of intestinal transit-amplifying and Lgr5+ stem cells and rapidly imposed features of aging, including hair loss, skin wrinkling, reduced body weight and subcutaneous fat, an increased myeloid fraction in peripheral blood, poor dentition, and cataracts. Aging features were observed with multiple combinations of p16 transgenes and transactivators and were largely abrogated by a germline Cdk4 R24C mutation, confirming that they reflect Cdk inhibition. Senescence markers were not found, and de-induction of p16, even after weeks of sustained expression, allowed rapid recovery of intestinal cell proliferation and reversal of aging features in most mice. These results suggest that p16-mediated inhibition of Cdk activity is sufficient to inhibit cell proliferation and impose aging features in somatic tissues of mammals and that at least some of these aging features are reversible.
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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.