Transcriptional changes of the aging lung.
Transcriptional changes of the aging lung.
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作者：
衰老是一个自然的过程，与器官功能下降和更容易患上慢性病有关。一项基于单细胞类型的系统性研究为理解年龄相关病理背后的机制提供了一个独特的机会。在这里，我们使用单细胞基因表达分析比较健康的年轻人和老年人来自不吸烟捐赠者的肺，以研究与年龄相关的转录变化。我们的数据表明，衰老对肺细胞具有异质性影响，因为一些群体在转录上更具活力，而另一些群体在老年个体中保持稳定。我们发现单核细胞和肺泡巨噬细胞是受转录影响最大的群体。这些变化与炎症和免疫反应的调节有关。此外，我们还计算了肺活量分数，揭示了衰老过程中肺细胞类型的多样性。DNA损伤修复、脂肪酸代谢和炎症的变化对年龄预测是必不可少的。最后，我们量化了老年肺的衰老分数，发现更倾向于衰老的细胞是免疫细胞和祖细胞。我们的研究对肺老化的分子特征进行了全面和系统的分析。我们的肺部信号可以用来预测生理性衰老的分子信号，并检测与年龄相关的肺部疾病的常见信号。单细胞RNA-SEQ分析发现，肺泡巨噬细胞和单核细胞是衰老肺中转录影响最大的细胞类型。此外，老年肺中的免疫细胞和祖细胞在所有细胞类型中显示出最高的衰老分数。肺部评分计算显示，DNA损伤修复、脂肪酸代谢和炎症的变化对于年龄预测是必不可少的。
Aging is a natural process associated with declined organ function and higher susceptibility to developing chronic diseases. A systemic single‐cell type‐based study provides a unique opportunity to understand the mechanisms behind age‐related pathologies. Here, we use single‐cell gene expression analysis comparing healthy young and aged human lungs from nonsmoker donors to investigate age‐related transcriptional changes. Our data suggest that aging has a heterogenous effect on lung cells, as some populations are more transcriptionally dynamic while others remain stable in aged individuals. We found that monocytes and alveolar macrophages were the most transcriptionally affected populations. These changes were related to inflammation and regulation of the immune response. Additionally, we calculated the LungAge score, which reveals the diversity of lung cell types during aging. Changes in DNA damage repair, fatty acid metabolism, and inflammation are essential for age prediction. Finally, we quantified the senescence score in aged lungs and found that the more biased cells toward senescence are immune and progenitor cells. Our study provides a comprehensive and systemic analysis of the molecular signatures of lung aging. Our LungAge signature can be used to predict molecular signatures of physiological aging and to detect common signatures of age‐related lung diseases. Single‐cell RNA‐seq analysis found that alveolar macrophages and monocytes are the most transcriptionally affected cell types in the aging lung. Additionally, immune and progenitor cells in the aged lung exhibit the highest senescence score among all cell types. LungAGe score calculations revealed that changes in DNA damage repair, fatty acid metabolism, and inflammation are essential for age prediction.
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CTCF 通过 POLD1 介导复制衰老
影响因子：
5.5
作者：
Hou Y;Song Q;Gao S;Zhang X;Wang Y;Liu J;Fu J;Cao M;Wang P
通讯作者：
Wang P
影响因子：
13.6
作者：
Hamsanathan S;Anthonymuthu T;Han S;Shinglot H;Siefken E;Sims A;Sen P;Pepper HL;Snyder NW;Bayir H;Kagan V;Gurkar AU
通讯作者：
Gurkar AU
DOI：
10.1183/13993003.02441-2018
发表时间：
2019-08
期刊：
The European respiratory journal
影响因子：
--
作者：
Morse C;Tabib T;Sembrat J;Buschur KL;Bittar HT;Valenzi E;Jiang Y;Kass DJ;Gibson K;Chen W;Mora A;Benos PV;Rojas M;Lafyatis R
通讯作者：
Lafyatis R
影响因子：
--
作者：
Prasse, Antje;Pechkovsky, Dmitri V.;Mueller-Quernheirn, Joachim
通讯作者：
Mueller-Quernheirn, Joachim
影响因子：
48
作者：
Korsunsky, Ilya;Millard, Nghia;Raychaudhuri, Soumya
通讯作者：
Raychaudhuri, Soumya