期刊
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
卷 319, 期 5, 页码 L755-L769出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajplung.00093.2020
关键词
acute lung injury; alveolar epithelial type II cells; cell senescence; pulmonary aging; surfactant
资金
- Deutsche Forschungsgemeinschaft (DFG) [BR5347/2-1]
- Bundesministerium fur Bildung und Forschung via the German Center for Lung Research
- Spanish Ministry of Science, Universities and Innovation [RTI2018-094564-B-100]
- Regional Government of Madrid [P2018/NMT-4389]
- DFG [BA5631/2-1]
Morbidity and mortality rates in acute lung injury (ALI) increase with age. As 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 mu g lipopolysaccharide/g body weight in young (3 mo) and old (18 mo) mice that were euthanized 24 h, 72 h, and 10 days later. Lung function, pulmonary surfactant activity, stereology, cell senescence, and singlecell RNA sequencing analyses were performed to investigate AE2 function in aging and ALI. In old mice, surfactant activity was severely Unpaired. A 60% mortality rate and lung function decline were observed 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 in young, mice, supporting an impaired regenerative capacity and reduced survival rate in ALI with advancing age.
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