ArticleThe Journal of clinical investigation2024
An in vivo screening platform identifies senolytic compounds that target p16INK4a+ fibroblasts in lung fibrosis.
Article in The Journal of clinical investigation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 39 citations in OpenAlex.
- Advances in pharmacotherapy for fibrotic interstitial lung disease.Medical review (2021) · 2026Review
- Ageing-associated regenerative failure in the lung: stem cell senescence and transitional cell persistence in idiopathic pulmonary fibrosis.European respiratory review : an official journal of the European Respiratory Society · 2026Review
- Targeting the senescence‒autophagy axis via p16Signal transduction and targeted therapy · 2026Article
- Insights into the therapeutic strategies for aging and aging-associated diseases.Signal transduction and targeted therapy · 2026Review
- Aberrant activation of tissue-resident lymphocytes and pro-fibrotic GZMK⁺ CD8⁺ T cells in IPF.Communications biology · 2026Article
- Upregulation of senescence-associated gene expression levels in human gingival tissue affected by periodontitis.Journal of periodontology · 2026Article
- Clearance of Senescent Cells by BCLAging cell · 2026Article
- Lung mTOR activation leads to lung fibrosis or emphysema via senescence of specific lung cells.Scientific reports · 2026Article
- p16-mediated G0/G1 cell cycle arrest leads to SASP and fibrosis in Fuchs endothelial corneal dystrophy.Cell death & disease · 2026Article
- The Mechanism of Oxidative Stress in Pulmonary Fibrosis and Research Progress.Antioxidants (Basel, Switzerland) · 2026Review
- Cellular senescence in Crohn's disease: a double-edged sword in intestinal fibrosis.Frontiers in immunology · 2026Review
- Beyond attenuation: a translational review of curative-intent pharmacological targets in idiopathic pulmonary fibrosis.Frontiers in medicine · 2026Review
- GSDME-dependent pyroptosis drives abdominal aortic aneurysm via promoting vascular senescence.Nature communications · 2025Article
- Senolytic-sensitive p16Cell stem cell · 2025Article
- Impact of the ATM/Chk2 pathway and cell cycle phase on radiation-induced senescence in A549 human lung cancer cells.Biomedical reports · 2025Article
- Stromal senescence contributes to age-related increases in cancer.Nature reviews. Cancer · 2025Review
- The Mechanism and Potential Therapeutic Strategies of Vascular Aging.Aging medicine (Milton (N.S.W)) · 2025Review
- Mechanosensing Pathways in the Progression of Pulmonary Fibrosis.Current opinion in biomedical engineering · 2025Article
- Nephronectin (NPNT) is a Crucial Determinant of Idiopathic Pulmonary Fibrosis: Modulating Cellular Senescence via the ITGA3/YAP1 Signaling Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Senotherapy for chronic lung disease.Pharmacological reviews · 2025Review
Corrections and comments
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
Abstract
The appearance of senescent cells in age-related diseases has spurred the search for compounds that can target senescent cells in tissues, termed senolytics. However, a major caveat with current senolytic screens is the use of cell lines as targets where senescence is induced in vitro, which does not necessarily reflect the identity and function of pathogenic senescent cells in vivo. Here, we developed a new pipeline leveraging a fluorescent murine reporter that allows for isolation and quantification of p16Ink4a+ cells in diseased tissues. By high-throughput screening in vitro, precision-cut lung slice (PCLS) screening ex vivo, and phenotypic screening in vivo, we identified a HSP90 inhibitor, XL888, as a potent senolytic in tissue fibrosis. XL888 treatment eliminated pathogenic p16Ink4a+ fibroblasts in a murine model of lung fibrosis and reduced fibrotic burden. Finally, XL888 preferentially targeted p16INK4a-hi human lung fibroblasts isolated from patients with idiopathic pulmonary fibrosis (IPF), and reduced p16INK4a+ fibroblasts from IPF PCLS ex vivo. This study provides proof of concept for a platform where p16INK4a+ cells are directly isolated from diseased tissues to identify compounds with in vivo and ex vivo efficacy in mice and humans, respectively, and provides a senolytic screening platform for other age-related diseases.
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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.