INTRODUCTION: The aging lung enters into a state of irreversible cellular growth arrest characterized by senescence. While senescence is beneficial in preventing oncogenic cell proliferation, it becomes detrimental when persistent, promoting chronic inflammation and fibrosis through the senescence-associated secretory phenotype (SASP). Such senescence-related pathophysiological processes play key roles in lung diseases like chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). However, few models accurately represent senescence in the human lung. METHODS: To generate a human lung senescence RESULTS: The doxorubicin-induced senescent hiPSC-derived lung cells demonstrated the hallmark characteristics of cellular senescence, including increased β-gal activity and increased production of the pro-inflammatory SASP cytokine IL-6 and increased secretion of TNF-α. Senescent cells displayed enlarged morphology, decreased proliferation, and reduced wound repair capacity. Barrier integrity was impaired with decreased electrical resistance, and increased permeability, as well as expression of abnormal tight junction proteins and increased fibrosis, all consistent with the senescent lung. CONCLUSION: Our hiPSC-derived lung cell senescent model reproduces key aspects of human lung senescence and offer an