<p>The prevalence and severity of asthma increase significantly with age; however, the fundamental processes are still not well understood. This study investigated the interplay between aging and asthma, specifically focusing on two critical pathways: activating NLR Family CARD domain containing 4 (NLRC4) inflammasome and transforming growth factor (TGF)-β1 signaling. Using age-specific mouse models (at 3, 13, and 23&#xa0;months) and hydrogen peroxide-induced senescent human bronchial epithelial cells, we demonstrated that aging significantly exacerbated both asthmatic inflammation and airway remodeling processes. Our analysis revealed age-dependent increases in inflammatory responses, particularly emphasizing enhanced eosinophil infiltration and elevated production of T-helper type 2 cytokines. Notably, the concurrent enhancement of both NLRC4 inflammasome activation and TGF-β1-mediated signaling in aged asthmatic mice and senescent cells. Elevation of these pathways manifests as heightened airway inflammation and substantial tissue remodeling, characterized by increased collagen deposition and enhanced expression of various fibrosis-related proteins. The increased NLRC4 inflammasome and TGF-β1 signaling are implied to be key factors contributing to the increased severity of asthma observed in elderly patients. This study suggests potential therapeutic approaches specifically targeted at managing asthma in the aging population by evaluating age-related molecular mechanisms of asthma pathogenesis.</p> Graphical abstract <p></p>