Targeting accelerated pulmonary ageing to treat chronic obstructive pulmonary disease-induced neuropathological comorbidities

Chronic obstructive pulmonary disease (COPD) is a major incurable health burden, ranking as the third leading cause of death worldwide, mainly driven by cigarette smoking. COPD is characterised by persistent airway inflammation, lung function decline and premature ageing with the presence of pulmonary senescent cells. This review proposes that cellular senescence, a state of stable cell cycle arrest linked to ageing, induced by inflammation and oxidative stress in COPD, extends beyond the lungs and affects the systemic circulation. This pulmonary senescent profile will reach other organs via extracellular vesicles contributing to brain inflammation and damage, and increasing the risk of neurological comorbidities, such as stroke, cerebral small vessel disease and Alzheimer's disease. The review explores the role of cellular senescence in COPD-associated brain conditions and investigates the relationship between cellular senescence and circadian rhythm in COPD. Additionally, it discusses potential therapies, including senomorphic and senolytic treatments, as novel strategies to halt or improve the progression of COPD.