Aging-dependent decrease in the numbers of enteric neurons, interstitial cells of Cajal and expression of connexin43 in various regions of gastrointestinal tract
Aging-dependent decrease in the numbers of enteric neurons, interstitial cells of Cajal and expression of connexin43 in various regions of gastrointestinal tract
复制标题
胃肠道各区域肠神经元、Cajal 间质细胞数量和 connexin43 表达的衰老依赖性减少
DOI：
10.18632/aging.101677
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发表时间：
2018-12
期刊：
影响因子：
5.2
通讯作者：
Zhou Deshan
中科院分区：
文献类型：
--
作者：
Sun Tingyi;Li D;an;Hu Shilong;Huang Li;Sun Haimei;Yang Shu;Wu Bo;Ji Fengqing;Zhou Deshan
衰老是胃肠运动障碍的重要危险因素，但不同器官之间与衰老相关的差异以及开始退化的确切时间仍然不清楚。在这里，我们评估了2、12、16、20和24月龄小鼠胃、空肠和结肠中Cajal间质细胞、肠神经元和connexin43表达的变化，以及老年人类结肠。随着时间的推移，整个消化道内Cajal神经元、胆碱能神经元和氮能神经元的间质细胞减少，但它们的减少首先出现在胃中，然后出现在肠中，这有助于理解胃功能在衰老过程中首先受损。connexin43的表达减少发生在Cajal间质细胞和神经元丢失之前，提示connexin43可能是衰老过程中受影响的主要靶点。此外，促炎因子（肿瘤坏死因子-α、白细胞介素-1β、白细胞介素-6）和凋亡相关蛋白（b细胞淋巴瘤-2、caspase-3）表达的变化表明“炎症”，这可能是老年胃肠道肠神经元和Cajal间质细胞丢失的原因。我们的结果为老年胃肠运动障碍患者的有益干预提供了可能的治疗时间窗口。
Aging is a significant risk factor for gastrointestinal dysmotility, but aging-associated differences between different organs and the exact time to start degenerating have remained obscure. Here we evaluated alterations of interstitial cells of Cajal, enteric neurons and connexin43 expression in the stomach, jejunum and colon in 2-, 12-, 16-, 20- and 24-month-old mice, as well as in aged human colon. Interstitial cells of Cajal, cholinergic and nitrergic neurons within the whole digestive tract were reduced over time, but their loss first appeared in stomach, then in intestine, helping to understand that gastric function was first impaired during aging. The decrease of connexin43 expression occurred before interstitial cells of Cajal and neurons loss, suggesting that connexin43 might be the major target influenced during senescence. Furthermore, changes in expressions of pro-inflammatory cytokines (tumour necrosis factor-α, interleukin-1β, interleukin-6) and apoptosis-related proteins (B-cell lymphoma-2, caspase-3) which indicated “inflammaging”, might contribute to the loss of enteric neurons and interstitial cells of Cajal in aged gastrointestinal tract. Our results provide possible therapeutic time window for beneficial intervention for geriatric patients with gastrointestinal motility disorders.
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DOI：
10.1038/nrgastro.2012.168
发表时间：
2012-11
期刊：
Nature reviews. Gastroenterology & hepatology
影响因子：
--
作者：
Sanders KM;Koh SD;Ro S;Ward SM
通讯作者：
Ward SM
影响因子：
3.5
作者：
Kashyap P;Gomez-Pinilla PJ;Pozo MJ;Cima RR;Dozois EJ;Larson DW;Ordog T;Gibbons SJ;Farrugia G
通讯作者：
Farrugia G
影响因子：
3.5
作者：
Zaitoun I;Erickson CS;Barlow AJ;Klein TR;Heneghan AF;Pierre JF;Epstein ML;Gosain A
通讯作者：
Gosain A
DOI：
10.1007/s00018-015-1961-8
发表时间：
2015-08
期刊：
Cellular and molecular life sciences : CMLS
影响因子：
--
作者：
Maes M;Cogliati B;Crespo Yanguas S;Willebrords J;Vinken M
通讯作者：
Vinken M
影响因子：
29.4
作者：
McClain J;Grubišić V;Fried D;Gomez-Suarez RA;Leinninger GM;Sévigny J;Parpura V;Gulbransen BD
通讯作者：
Gulbransen BD