Cellular senescence is a stress-induced type of irreversible cell cycle arrest, driven by telomere attrition, oxidative stress, DNA damage, mitochondrial dysfunction, oncogene activation, and chronic inflammation. Senescent cells remain metabolically active, secreting cytokines, chemokines, growth factors, matrix metalloproteinases, extracellular vesicles and oxidative mediators, comprising a senescence-associated secretory phenotype (SASP) that affects the tissue microenvironment. With aging, impaired immune clearance results in senescent cell accumulation, promoting inflammation, immunosuppression and fibrosis. Emerging evidence implicates cellular senescence in obstructive airway diseases, reflecting the lung’s continuous exposure to environmental and oxidative insults, and several pathways, including DNA damage response and p53/p21 and p16INK4a signaling, telomere dysfunction, reactive oxygen species production, and mitochondrial defects, integrate stress signals to enforce senescence. In chronic obstructive pulmonary disease, a SASP-associated inflammatory milieu supports stress-induced tissue injury, while uncertainty still exists about the effects of chronic SASP on tumor suppression versus tumor promotion. In asthma, senescence processes have been associated with both Type(T)2-high and T2-low endotypes, underlying the interplay between environmental exposures, airway epithelial dysfunction and induced senescence mechanisms. Finally, in bronchiectasis, the neutrophilic, dysbiotic airway environment links dysregulated senescence with disease persistence and progression. Conventional therapies, antioxidants, serine protease inhibitors and novel senotherapeutic strategies represent promising approaches for therapeutic interventions.
Vrouvaki et al. (Thu,) studied this question.