Targeting Hyperoxia‐Induced Cellular Senescence in Developing Human Airway Cells: Senomorphics Versus Senolytics Versus Antioxidants

) were treated with Fucoidan [100 μg/mL], D + Q [250 nM + 375 nM] or MitoQ [100 nM] and assessed for senescence markers, senescence-associated secretory profile (SASP), extracellular matrix (ECM) deposition, and cell viability. Our results showed that moderate hyperoxia increases senescence markers and SASP. Fucoidan decreased p21 expression and inhibited SASP release without inducing cell death, while D + Q decreased β-galactosidase (β-Gal) activity, p21 and plasminogen activator inhibitor-1 (PAI-1) expression, and caused cell death without affecting SASP in hyperoxia-induced senescent fASM. MitoQ prevented increases in senescence markers and SASP in hyperoxia-exposed fASM. These findings demonstrate distinct and viable strategies to counter hyperoxia-induced fASM senescence. Fucoidan (senomorphic), D + Q (senolytic), and MitoQ (prophylactic antioxidant) represent promising, mechanistically different approaches to alleviate detrimental effects of moderate hyperoxia in developing airways towards limiting perinatal lung disease.