Targeting Hyperoxia-Induced Cellular Senescence in Developing Human Airway Cells: Senomorphics Versus Senolytics
Maunick Lefin Koloko Ngassie1, Li Y Drake1, Yi Zhu2
1Department of Anesthesiology and Perioperative Medicine, Rochester, Minnesota, USA.
Aging Cell
|May 8, 2026
Summary
Supplemental oxygen can harm premature infant lungs by causing cellular senescence. Senotherapeutics like Fucoidan and Dasatinib+Quercetin, and antioxidant MitoQ, show promise in preventing or reversing this damage in airway cells.
Area of Science:
- Pulmonary Medicine
- Cellular Biology
- Neonatology
Background:
- Supplemental oxygen (hyperoxia) can impair lung development in premature infants, leading to neonatal and pediatric lung diseases.
- Moderate hyperoxia induces cellular senescence in human fetal airway smooth muscle (fASM) cells, impacting airway contractility and remodeling.
Purpose of the Study:
- To investigate the efficacy of senotherapeutics (Fucoidan, Dasatinib+Quercetin) and a mitochondrial antioxidant (MitoQ) in mitigating hyperoxia-induced senescence in fASM cells.
- To assess the impact of these treatments on senescence markers, senescence-associated secretory profile (SASP), extracellular matrix (ECM) deposition, and cell viability.
Main Methods:
- Human fetal airway smooth muscle (fASM) cells were exposed to normoxia (21% O2) or hyperoxia (50% O2).
- Cells were treated with Fucoidan, Dasatinib+Quercetin (D+Q), or MitoQ.
- Assessed senescence markers, SASP, ECM deposition, and cell viability.
Main Results:
- Hyperoxia increased senescence markers and SASP in fASM cells.
- Fucoidan reduced p21 expression and inhibited SASP without causing cell death.
- D+Q reduced β-galactosidase activity, p21, and PAI-1 but induced cell death without affecting SASP.
- MitoQ prevented hyperoxia-induced increases in senescence markers and SASP.
Conclusions:
- Fucoidan acts as a senomorphic agent, D+Q as a senolytic agent, and MitoQ as a prophylactic antioxidant.
- These distinct therapeutic strategies show promise in counteracting hyperoxia-induced fASM senescence.
- These approaches could help alleviate detrimental effects of hyperoxia in developing airways, potentially limiting perinatal lung disease.
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