The Aging Human Lung Mucosa: A Proteomics Study.
The Aging Human Lung Mucosa: A Proteomics Study.
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衰老的人类肺粘膜：蛋白质组学研究。
DOI：
10.1093/gerona/glac091
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Torr
中科院分区：
文献类型：
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作者：
Garcia-Vilanova,Andreu;Olmo-Fontánez,AngélicaM;Moliva,JuanI;Allué-Guardia,Anna;Singh,Harjinder;Merritt,RobertE;Maselli,DiegoJ;Peters,JayI;Restrepo,BlancaI;Wang,Yufeng;Schlesinger,LarryS;Turner,Joanne;Weintraub,SusanT;Torr
据估计，到2050年，老年人口将翻一番，他们患呼吸道感染和其他肺部疾病的风险增加。随着我们年龄的增长，肺泡衬里液体(ALF)和肺泡室细胞中的生化变化可以改变局部免疫反应，为入侵的病原体建立成功的感染创造机会。事实上，老年人的肺泡空间是一个促炎、促氧化、调节失调的环境，目前仍未得到充分研究。我们对ALF中存在的可溶性蛋白质进行了探索性的、定量的蛋白质组学分析，深入了解了表征老年人肺泡空间的分子指纹、通路和调节网络，并将其与年轻个体进行了比较。我们鉴定了457种在老年人ALF中显著差异表达的蛋白质，包括基质金属蛋白酶、细胞衰老标记物、抗菌剂和中性粒细胞起源的蛋白质等的产生增加，这表明随着年龄的增长，老年人肺中的中性粒细胞可能是调节失调的肺泡环境的潜在贡献者。最后，我们描述了一个由血清反应因子介导的假想调节网络，该网络可以解释在老年人群中观察到的中性粒细胞分布。
The older adult population, estimated to double by 2050, is at increased risk of respiratory infections and other pulmonary diseases. Biochemical changes in the lung alveolar lining fluid (ALF) and in alveolar compartment cells can alter local immune responses as we age, generating opportunities for invading pathogens to establish successful infections. Indeed, the lung alveolar space of older adults is a pro-inflammatory, pro-oxidative, dysregulated environment that remains understudied. We performed an exploratory, quantitative proteomic profiling of the soluble proteins present in ALF, developing insight into molecular fingerprints, pathways, and regulatory networks that characterize the alveolar space in old age, comparing it to that of younger individuals. We identified 457 proteins that were significantly differentially expressed in older adult ALF, including increased production of matrix metalloproteinases, markers of cellular senescence, antimicrobials, and proteins of neutrophilic granule origin, among others, suggesting that neutrophils in the lungs of older adults could be potential contributors to the dysregulated alveolar environment with increasing age. Finally, we describe a hypothetical regulatory network mediated by the serum response factor that could explain the neutrophilic profile observed in the older adult population.