{"id":"doi:10.1038/ncomms14532","kind":"article","title":"Cellular senescence mediates fibrotic pulmonary disease","authors":["Schafer MJ","White TA","Iijima K","Haak AJ","Ligresti G","Atkinson EJ","Oberg AL","Birch J","Salmonowicz H","Zhu Y","Mazula DL","Brooks RW","Fuhrmann-Stroissnigg H","Pirtskhalava T","Prakash YS","Tchkonia T","Robbins PD","Aubry MC","Passos JF","Kirkland JL","Tschumperlin DJ","Kita H","LeBrasseur NK"],"author_count":23,"year":2017,"published":"2017-02-23","venue":"Nature communications","cited_by":1435,"doi":"10.1038/ncomms14532","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1038/ncomms14532","archive_url":"https://space-kitty.com/papers/doi:10.1038/ncomms14532","updated":null,"pmid":"28230051","pmcid":"PMC5331226","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC5331226/pdf","abstract":"Idiopathic pulmonary fibrosis (IPF) is a fatal disease characterized by interstitial remodelling, leading to compromised lung function. Cellular senescence markers are detectable within IPF lung tissue and senescent cell deletion rejuvenates pulmonary health in aged mice. Whether and how senescent cells regulate IPF or if their removal may be an efficacious intervention strategy is unknown. Here we demonstrate elevated abundance of senescence biomarkers in IPF lung, with p16 expression increasing with disease severity. We show that the secretome of senescent fibroblasts, which are selectively killed by a senolytic cocktail, dasatinib plus quercetin (DQ), is fibrogenic. Leveraging the bleomycin-injury IPF model, we demonstrate that early-intervention suicide-gene-mediated senescent cell ablation improves pulmonary function and physical health, although lung fibrosis is visibly unaltered. DQ treatment replicates benefits of transgenic clearance. Thus, our findings establish that fibrotic lung disease is mediated, in part, by senescent cells, which can be targeted to improve health and function.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"Cellular senescence mediates fibrotic pulmonary disease\" by Schafer MJ, White TA, Iijima K et al., https://doi.org/10.1038/ncomms14532, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.","topics":[{"slug":"aging-longevity","name":"Biology of Aging & Longevity","domain_slug":"medicine"}],"cited_in_dossiers":[]}