Senescence-driven pathogenesis in chronic lung diseases: from mechanistic insights to translational approaches

Abstract

Chronic lung diseases (CLDs) include a variety of disorders of the pulmonary vasculature and alveolar compartments, and they have become a considerable global health challenge due to their high morbidity and limited therapeutic options. Increasing evidence shows that cellular senescence, an irreversible cell-cycle arrest accompanied by altered secretory activity and resistance to apoptosis, plays a crucial role in the onset and progression of CLDs. One of the major consequences of senescence-associated secretory phenotype activity in senescent cells is the further exacerbation of CLD pathogenesis through the maintenance of chronic inflammation, tissue remodeling, and structural vascular changes. Although individual CLDs exhibit distinct pathological features, they share common mechanisms, including persistent inflammation and dysregulated tissue repair. Experimental models and new methods have advanced, demonstrating the promise of targeted approaches, such as senolytics and regulators of senescence-associated traits, for treating these diseases. This review evaluates how cell senescence is involved with pulmonary arterial hypertension, pulmonary fibrosis and chronic obstructive pulmonary disease, highlights both shared and different pathologic routes, and discusses using seno-therapeutic methods within precision medicine plans.

Keywords

Cellular senescence / chronic lung diseases / pulmonary arterial hypertension / pulmonary fibrosis / chronic obstructive pulmonary disease

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