Mechanism | Ageing | COPD |
Oxidative stress | Neutrophils, macrophages and monocytes show enhanced ROS production [89, 90] | Increased oxidative stress in the lungs promoting inflammation [74, 75, 91, 92] |
Telomere shortening is enhanced by oxidative stress [33, 93] | ||
Telomere length | Decreased telomere length in peripheral blood leukocytes [94] | Telomere length is smoking dose-dependent; telomere length is shorter in peripheral blood leukocytes in COPD and emphysema [76, 77, 93, 95] |
Tissue-specific cellular senescence | Induced when a critical telomere length is reached [96] | Elevated SA-β-Gal, p21CIP1/WAP1/sdi1 and pro-inflammatory cytokine production in lung parenchyma and type II alveolar cells [78, 80] |
Inflammatory cytokines | Persistent low-level inflammation: IL-6, TNF-α and acute-phase reactants [97] | Increased systemic and pulmonary levels of IL-6, TNF-α and CRP [98, 99] |
Neutrophils | Unchanged numbers and impaired killing [100] | Increased in BALF and lung parenchyma [100] |
Macrophages/monocytes | Deficient TLR signalling, less production of pro-inflammatory cytokines [90, 101, 102] | Increased in airways and lung parenchyma, and production of pro-inflammatory cytokines [100] |
Dendritic cells | Changed phenotype, increased levels of pro-inflammatory cytokines [103, 104] | More active in COPD [105] |
T-cells | The proportion of memory cells that are CD28null (senescent phenotype) increases and decreases the numbers of naïve T-cells [106] | Senescent T-cell phenotype and repertoire contraction [107]; less ability to fight infections |
B-cells | Decreased B-cell production and impaired ability to undergo immunoglobulin class switch [108] |
ROS: reactive oxygen species; SA-β-Gal: senescence-associated β-galactosidase; IL: interleukin; TNF: tumour necrosis factor; CRP: C-reactive protein; BALF: bronchoalveolar lavage fluid; TLR: Toll-like receptor.