Evidence for ageing hallmarks in chronic obstructive pulmonary disease (COPD)

HallmarkMarkerCOPD versus non-COPDCOPD cell originCSE-treated cellsReferences
Genomic instabilityγ-H2A.XLung tissue sections, AT1, AT2, HBEC and PV-ECHBEC, HFL1 and MRC-5[75, 76, 78, 79]
Ku70Peripheral leukocytes[80]
Ku80Lung homogenates[77]
Telomere shorteningLengthLung homogenates AT2, PA-SMC, PV-EC and peripheral leukocytesSAEC (COPD) and HFL1[78, 81–86]
TPP1Lung homogenatesSAEC and HFL1[78]
Epigenetic changesHDAC activityLung homogenates and bronchial biopsies[92]
SIRT1 and -6Lung homogenates[94, 95]
Loss of proteostasisAutophagyHBECSAEC[100]
AutophagyHBEC (COPD)[100]
AutophagosomesLung homogenatesHBEC and BEAS-2B[79, 99, 100]
UbiquitinLung homogenates[98, 100]
p62Lung homogenates[79, 100]
Deregulated nutrient sensingS6K (mTOR)#Lung homogenates and peripheral leukocytesHBEC[79, 103]
Mitochrondrial dysfunctionROSHBEC, BEAS-2B and MRC-5[76, 108, 109]
Oxidised DNALung homogenates[77]
Lipid peroxidationLung homogenates[105, 106]
Nitric oxideLung homogenates[106]
MitophagyLung homogenatesHBEC and BEAS-2B[108, 109]
AntioxidantLung homogenates and HBEC[107]
Mitochondrial membrane potentialBEAS-2B[108]
Immune dysregulationKlothoLung homogenatesHBEC[112]
NF-κBLung homogenates[113]
Pro-inflammatory cytokinesLung homogenates[113]
SenescenceSA-β-galSAEC, PA-SMC, PV-EC and fibroblastsSAEC (COPD), HBEC, A549, HFL1 and MRC-5[76, 78, 79, 84–86, 115–117]
p16Lung tissue sections, AT1, AT2, PA-SMC, PV-EC and fibroblastsHFL1[75, 76, 78, 84–86, 116, 117]
p21Lung homogenates, AT2, PA-SMC, PV-EC and peripheral leukocytesHBEC, A549 and HFL1[78–80, 84–86, 117]
IL-6 and IL-8Lung tissue sections, AT1, AT2, PA-SMC and PV-ECMRC-5[75, 76, 84, 85]
ECM dysregulationECM proteinsLung homogenates[42]
Elastogenesis genesLung homogenates[125]
MMP/TIMP dysregulationLung homogenates[123]
Stem cell exhaustionCirculating progenitor cells#Endothelial and haemopoietic progenitor cells[137, 138]
Regenerative capacityBasal progenitor cells[135]
Stem cell functionHBEC[142]
WNT signalling#Lung homogenates, AT2 and SAEC[144, 147]
Notch pathway#SAEC[143]

CSE: cigarette smoke extract; AT1: type I alveolar cells; AT2: type II alveolar cells; HBEC: human bronchial epithelial cells; PV-EC: pulmonary vascular endothelial cells; HFL1: fetal lung fibroblasts; MRC-5: fetal lung fibroblasts; TPP1: telomere protection protein 1; PA-SMC: pulmonary artery smooth muscle cells; SAEC: small airway epithelial cells; HDAC: histone deacetylase; SIRT: sirtuin; BEAS-2B: bronchial epithelial cell line (virus); mTOR: mechanistic target of rapamycin; IGF1: insulin-like growth factor 1; ROS: reactive oxygen species; SA-β-gal: senescence-associated-β-galactosidase; IL: interleukin; A549: alveolar basal epithelial cell line (carcinoma); ECM: extracellular matrix; MMP: matrix metalloproteinase; TIMP: tissue inhibitor of metalloproteinase. #: mean age was significantly different between COPD and control group; for the other studies, information was not available or mean age was not different between groups.