Morbidity and mortality rates in acute lung injury (ALI) increase with age. Since alveolar epithelial type II cells (AE2) are crucial for lung function and repair, we hypothesized that aging promotes senescence in AE2 and contributes to the severity and impaired regeneration in ALI. ALI was induced with 2.5 μg lipopolysaccharide/g body weight in young (3 months) and old (18 months) mice that were sacrificed 24 h, 72 h and 10 d later. Lung function, pulmonary surfactant activity, stereology, cell senescence and single cell RNA sequencing analyses were performed to investigate AE2 function in aging and ALI. In old mice, surfactant activity was severely impaired. A 60% mortality rate and lung function decline was present in old, but not in young mice with ALI. AE2 of young mice adapted to injury by increasing intracellular surfactant volume and proliferation rate. In old mice, however, this adaptive response was compromised and AE2 of old mice showed signs of cell senescence, increased inflammatory signaling and impaired surfactant metabolism in ALI. These findings provide evidence that ALI promotes a limited proliferation rate, increased inflammatory response and surfactant dysfunction in old, but not young mice, supporting an impaired regenerative capacity and reduced survival rate in ALI with advancing age.

中文翻译：

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在急性肺损伤中，衰老会损害肺泡II型上皮细胞功能。

急性肺损伤（ALI）的发病率和死亡率随年龄增长而增加。由于肺泡II型上皮细胞（AE2）对于肺功能和修复至关重要，因此我们假设衰老会促进AE2的衰老，并导致ALI的严重性和受损的再生。在幼鼠（3个月）和老年（18个月）小鼠中，2.5 g脂多糖/ g体重诱导ALI，在24、72和10 d后处死小鼠。进行了肺功能，肺表面活性剂活性，立体学，细胞衰老和单细胞RNA测序分析，以研究AE2在衰老和ALI中的功能。在老年小鼠中，表面活性剂活性严重受损。在患有ALI的老年小鼠中，死亡率为60％，肺功能下降。幼鼠的AE2通过增加细胞内表面活性剂的体积和增殖速率来适应损伤。然而，在老年小鼠中，这种适应性反应受到损害，老年小鼠的AE2显示出细胞衰老的迹象，炎症信号增强和ALI中表面活性剂代谢受损。这些发现提供了证据，表明ALI可促进衰老小鼠的增殖速率受限，炎症反应增加和表面活性剂功能障碍，但对年幼小鼠却不起作用，这支持了随着年龄的增长，ALI的再生能力受损，存活率降低。