{
  "abstract": "Background Idiopathic pulmonary fibrosis (IPF) is a progressive disease of lung parenchymal scarring that is triggered by repeated microinjury to a vulnerable alveolar epithelium. It is increasingly recognised that cellular ageing, whether physiological or accelerated due to telomere dysfunction, renders the epithelium less able to cope with injury and triggers changes in epithelial behaviour that ultimately lead to the development of disease.Aims This review aims to highlight how, with increasing age, the alveolar epithelium becomes vulnerable to exogenous insults. We discuss the downstream consequences of alveolar epithelial dysfunction on epithelial phenotype, alveolar repair and pro-pathogenic interactions with other alveolar niche-resident cell types which drive IPF pathogenesis.Narrative We highlight how a wide array of cellular mechanisms that maintain cellular homeostasis become dysfunctional with ageing. Waning replicative capacity, genomic stability, mitochondrial function, proteostasis and metabolic function all contribute to a phenotype of vulnerability to ‘second hits’. We discuss how in IPF the alveolar epithelium becomes dysfunctional, highlighting changes in repair capacity and fundamental cellular phenotype and how interactions between abnormal epithelium and other alveolar niche-resident cell types perpetuate disease.Conclusions The ageing epithelium is a vulnerable epithelium which, with the cumulative effects of environmental exposures, fundamentally changes its behaviour towards stalled differentiation, failed repair and profibrotic signalling. Further dissection of aberrant epithelial behaviour, and its impact on other alveolar cell types, will allow identification of novel therapeutic targets aimed at earlier pathogenic events.",
  "authors": [
    {
      "affiliations": [
        "King’s Centre for Lung Health, King’s College London, London, UK"
      ],
      "name": "Richard J Hewitt"
    },
    {
      "affiliations": [
        "Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK",
        "ILD Unit, North West Lung Centre, Wythenshawe Hospital, Manchester Foundation Trust, Manchester, UK"
      ],
      "name": "Laurence Pearmain"
    },
    {
      "affiliations": [
        "Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK"
      ],
      "name": "Elisavet Lyka"
    },
    {
      "affiliations": [
        "Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK",
        "Cambridge Institiute for Medical Research, University of Cambridge, Cambridge, UK",
        "Royal Papworth NHS Foundation Trust, Cambridge, UK"
      ],
      "name": "Jennifer Dickens"
    }
  ],
  "title": "Epithelial damage and ageing: the perfect storm",
  "uid": "f6ac8e44-9b7c-5b30-bcdf-c12e1f0c4ded"
}