IPF lung fibroblasts have a senescent phenotype

Am J Physiol Lung Cell Mol Physiol. 2017 Dec 1;313(6):L1164-L1173. doi: 10.1152/ajplung.00220.2017. Epub 2017 Aug 31.


The mechanisms of aging that are involved in the development of idiopathic pulmonary fibrosis (IPF) are still unclear. Although it has been hypothesized that the proliferation and activation of human lung fibroblasts (hLFs) are essential in IPF, no studies have assessed how this process works in an aging lung. Our goal was to elucidate if there were age-related changes on primary hLFs isolated from IPF lungs compared with age-matched controls. We investigated several hallmarks of aging in hLFs from IPF patients and age-matched controls. IPF hLFs have increased cellular senescence with higher expression of β-galactosidase, p21, p16, p53, and cytokines related to the senescence-associated secretory phenotype (SASP) as well as decreased proliferation/apoptosis compared with age-matched controls. Additionally, we observed shorter telomeres, mitochondrial dysfunction, and upon transforming growth factor-β stimulation, increased markers of endoplasmic reticulum stress. Our data suggest that IPF hLFs develop senescence resulting in a decreased apoptosis and that the development of SASP may be an important contributor to the fibrotic process observed in IPF. These results might change the existing paradigm, which describes fibroblasts as aberrantly activated cells, to a cell with a senescence phenotype.

Keywords: TGF-β; aging; collagen; fibroblasts; idiopathic pulmonary fibrosis; mitochondria; senescence; telomeres.

MeSH terms

  • Adult
  • Aging / metabolism*
  • Aging / pathology
  • Cell Line
  • Cellular Senescence*
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • Cytokines / metabolism
  • Female
  • Fibroblasts / metabolism*
  • Fibroblasts / pathology
  • Humans
  • Idiopathic Pulmonary Fibrosis / metabolism*
  • Idiopathic Pulmonary Fibrosis / pathology
  • Lung / metabolism*
  • Lung / pathology
  • Male
  • Middle Aged
  • Tumor Suppressor Protein p53 / metabolism
  • beta-Galactosidase / metabolism


  • CDKN1A protein, human
  • CDKN2A protein, human
  • Cyclin-Dependent Kinase Inhibitor p16
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cytokines
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • beta-Galactosidase