2015
DOI: 10.18632/aging.100807
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Abstract: Idiopathic pulmonary fibrosis (IPF) is an age-related fatal disease with unknown etiology and no effective treatment. In this study, we show that primary cultures of fibroblasts derived from lung biopsies of IPF patients exhibited (i) accelerated replicative cellular senescence (CS); (ii) high resistance to oxidative-stress-induced cytotoxicity or CS; (iii) a CS-like morphology (even at the proliferative phase); and (iv) rapid accumulation of senescent cells expressing the myofibroblast marker α-SMA. Our findi… Show more

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Cited by 111 publications
(90 citation statements)
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References 41 publications
(57 reference statements)
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“…Consistent with studies in mouse models, fibroblasts and lung epithelial cells from IPF lungs express markers of senescence, including positive β-gal staining and p21 expression (23,71,78). However, the majority of the current studies with human lung fibroblasts lack appropriate age-matched controls to determine whether the senescent and profibrotic phenotype is related to advanced age.…”
Section: Cellular Perturbations In the Ipf Lungsupporting
confidence: 53%
See 1 more Smart Citation
“…Consistent with studies in mouse models, fibroblasts and lung epithelial cells from IPF lungs express markers of senescence, including positive β-gal staining and p21 expression (23,71,78). However, the majority of the current studies with human lung fibroblasts lack appropriate age-matched controls to determine whether the senescent and profibrotic phenotype is related to advanced age.…”
Section: Cellular Perturbations In the Ipf Lungsupporting
confidence: 53%
“…OGG1 is a DNA repair differently (Table 3). For example, senescence can be responsible for exhaustion of stem cells (69), secretion of inflammatory mediators in immune cells and fibroblasts (70), and increased myofibroblast differentiation in lung fibroblasts (71). Stressinduced senescence has been observed in isolated mouse lung fibroblasts from fibrotic lungs, although their proliferative capacity vary between studies.…”
Section: Cellular Perturbations In the Ipf Lungmentioning
confidence: 99%
“…Moreover, senescent cells might be harmful and contribute to tissue remodelling, ageing and age-related diseases. In this context, alveolar epithelial and lung fibroblasts with a senescent phenotype are a prominent feature of IPF [111][112][113][114][115] .…”
Section: Senescence and Saspmentioning
confidence: 99%
“…Recently, a new paradigm that helps explain the increased prevalence of fibrosis with aging has emerged, suggesting that fibrosis results from the accumulation and decreased turnover of senescent fibroblasts. Fibroblasts from patients with IPF have decreased proliferation and apoptosis than normal fibroblasts, are more resistant to oxidative stress, and exhibit morphological features of cellular senescence [127, 128]. Markers of cellular senescence such as β-galactosidase, p16, and p21 are increased in fibroblasts from patients with IPF and in murine lung fibrosis [128, 129], and the secretome (SASP) of senescent fibroblasts is profibrotic [129].…”
Section: Sirtuins and Sclerodermamentioning
confidence: 99%