Table 1– Mechanisms of ageing in the pathogenesis of chronic obstructive pulmonary disease (COPD)

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, p21^{CIP1/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 CD28^null (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.