Cellular senescence in chronic obstructive pulmonary disease: Molecular mechanisms and therapeutic interventions

Chronic obstructive pulmonary disease (COPD) is the world's fourth highest reason for mortality, accounting for 3.5 million deaths in 2021, and about 5 % of total global deaths. Emphysema and chronic bronchitis are the two major pathologies of COPD. Tobacco smoke, dust, vapors, and fumes, outdoor air pollutants, genetic factors, ageing, infections, and asthma are the risk factors of COPD. On the other hand, senescence is permanent halt in cell cycle accompanied by phenotypic alterations due to ageing, oxidative stress like; irreparable DNA damage, telomere shortening, oncogene activation or inactivation of tumor suppressors. COPD is often considered an accelerated ageing process of the lungs, with senescent cells impairing tissue repair and regeneration, causing progressive lung function decline. Although, cellular senescence is seen as powerful defense against risk of carcinogenesis in COPD as it arrests cell proliferation irreversibly, excessive collection of senescent cells releases senescence-associated secretory phenotype (SASP) that increase oxidative stress to lungs and leads to long-term inflammation, tissue damage, and hindered lung recovery. This review will address the accelerated ageing process and cellular senescence in COPD, therapeutic approaches targeting senescence regulation in COPD; clinical research and trial studies demonstrating the use of therapies aimed at senescence in COPD along with current obstacles and potential solutions.