Aspirin Positively Contributes to Drosophila Intestinal Homeostasis and Delays Aging through Targeting Imd.
Aspirin Positively Contributes to Drosophila Intestinal Homeostasis and Delays Aging through Targeting Imd.
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阿司匹林通过靶向 IMD 积极促进果蝇肠道稳态并延缓衰老
DOI：
10.14336/ad.2020.1008
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发表时间：
2021-10
影响因子：
7.4
通讯作者：
Ji S
中科院分区：
文献类型：
--
作者：
Zhu Y;Cai Q;Zheng X;Liu L;Hua Y;Du B;Zhao G;Yu J;Zhuo Z;Xie Z;Ji S
肠道是一种高周转组织，在调节脊椎动物和无脊椎动物的衰老和健康方面起着关键作用。通过保持先天免疫稳态来维持肠上皮屏障功能，可显著延缓衰老并预防死亡。在努力探索有效的化学物质和材料，可以改善肠道的完整性，我们进行了无偏见的屏幕使用果蝇作为动物模型。我们发现，长期服用阿司匹林可以显著预防果蝇年龄发作性肠漏、肠道干细胞过度增殖和肠道微生物群失调。从机制上讲，阿司匹林有效地下调了衰老过程中肠道免疫缺陷信号的慢性激活。此外，我们在体内和体外的生化分析表明，阿司匹林是一个负调制器在控制K63连接的泛素化的Imd。我们的研究结果揭示了一种新的调节机制，阿司匹林积极调节肠道内稳态，从而延缓衰老，在果蝇。
The intestine, a high-turnover tissue, plays a critical role in regulating aging and health in both vertebrates and invertebrates. Maintaining the epithelial barrier function of the intestine by preserving innate immune homeostasis significantly delays aging and prevents mortality. In an effort to explore effective chemicals and materials that can improve intestinal integrity, we performed a nonbiased screen utilizing Drosophila as an animal model. We showed that long-term uptake of aspirin markedly prevented age-onset gut leakage, the over-proliferation of intestinal stem cells, and the dysbiosis of commensal microbiota in fruit flies. Mechanistically, aspirin efficiently downregulated chronic activation of intestinal immune deficiency signaling during aging. Furthermore, our in vivo and in vitro biochemical analyses indicated that aspirin is a negative modulator in control of the K63-linked ubiquitination of Imd. Our findings uncover a novel regulatory mechanism by which aspirin positively modulates intestinal homeostasis, thus delaying aging, in Drosophila.