Lung cellular senescence is independent of aging in a mouse model of COPD/emphysema.
Lung cellular senescence is independent of aging in a mouse model of COPD/emphysema.
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DOI：
10.1038/s41598-018-27209-3
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发表时间：
2018-06-13
影响因子：
4.6
通讯作者：
Rahman I
中科院分区：
文献类型：
--
作者：
Rashid K;Sundar IK;Gerloff J;Li D;Rahman I
香烟烟雾（CS）诱导肺细胞衰老在慢性阻塞性肺疾病（COPD）的发病机制中起重要作用。衰老如何影响细胞衰老和其他分子标志，并增加CS诱导损伤的风险仍然未知。我们假设年龄相关的肺部变化会使CS暴露导致COPD/肺气肿恶化。年轻和老年组的C57 BL/6 J小鼠暴露于慢性CS 6个月，各自年龄匹配的空气暴露对照。CS引起肺功能下降，并影响两组小鼠的肺结构。在暴露于空气中的年轻人和老年人对照组之间，没有观察到炎症介质的诱导发生变化，但衰老增加了CS诱导的肺部炎症的严重程度。衰老本身增加了肺细胞衰老和损伤相关分子模式标志物S100 A8的显著变化。使用nanoString nCounter进行的基因转录分析显示，CS显著上调了关键的促衰老靶点（Mmp 12、Ccl 2、Cdkn 2a、Tert、Bubn和Bub 1b）。老化独立影响肺功能和结构，以及增加易感性CS诱导的炎症肺气肿，但有一个可以忽略不计的影响细胞衰老。因此，在COPD/肺气肿的小鼠模型中，衰老本身并不有助于CS诱导细胞衰老。
Cigarette smoke (CS) induces lung cellular senescence that plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). How aging influences cellular senescence and other molecular hallmarks, and increases the risk of CS-induced damage remains unknown. We hypothesized that aging-associated changes in lungs worsen the COPD/emphysema by CS exposure. Younger and older groups of C57BL/6J mice were exposed to chronic CS for 6 months with respective age-matched air-exposed controls. CS caused a decline in lung function and affected the lung structure of both groups of mice. No alterations were observed in the induction of inflammatory mediators between the air-exposed younger and older controls, but aging increased the severity of CS-induced lung inflammation. Aging per se increased lung cellular senescence and significant changes in damage-associated molecular patterns marker S100A8. Gene transcript analysis using the nanoString nCounter showed a significant upregulation of key pro-senescence targets by CS (Mmp12, Ccl2, Cdkn2a, Tert, Wrn, and Bub1b). Aging independently influenced lung function and structure, as well as increased susceptibility to CS-induced inflammation in emphysema, but had a negligible effect on cellular senescence. Thus, aging solely does not contribute to the induction of cellular senescence by CS in a mouse model of COPD/emphysema.
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影响因子：
3.7
作者：
HAYFLICK, L;MOORHEAD, PS
通讯作者：
MOORHEAD, PS
DOI：
10.1073/pnas.92.20.9363
发表时间：
1995-09-26
影响因子：
11.1
作者：
DIMRI, GP;LEE, XH;CAMPISI, J
通讯作者：
CAMPISI, J
DOI：
10.1165/rcmb.2016-0198oc
发表时间：
2017-01-01
影响因子：
6.4
作者：
Ahmad, Tanveer;Sundar, Isaac K.;Rahman, Irfan
通讯作者：
Rahman, Irfan
DOI：
10.1111/j.1365-2362.2012.02646.x
发表时间：
2012-08-01
影响因子：
5.5
作者：
Gopal, Poornima;Rutten, Erica P. A.;Reynaert, Niki L.
通讯作者：
Reynaert, Niki L.
影响因子：
11.8
作者：
Demaria, Marco;Ohtani, Naoko;Youssef, Sameh A.;Rodier, Francis;Toussaint, Wendy;Mitchell, James R.;Laberge, Remi-Martin;Vijg, Jan;Van Steeg, Harry;Dolle, Martijn E. T.;Hoeijmakers, Jan H. J.;de Bruin, Alain;Hara, Eiji;Campisi, Judith
通讯作者：
Campisi, Judith