Chemical activation of a food deprivation signal extends lifespan.
Chemical activation of a food deprivation signal extends lifespan.
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DOI：
10.1111/acel.12492
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发表时间：
2016-10
期刊：
影响因子：
7.8
通讯作者：
Lithgow GJ
中科院分区：
文献类型：
--
作者：
Lucanic M;Garrett T;Yu I;Calahorro F;Asadi Shahmirzadi A;Miller A;Gill MS;Hughes RE;Holden-Dye L;Lithgow GJ
受饮食限制（DR）的模式生物通常寿命更长。伴随着这种寿命延长的是基于多个指标的整体健康状况的改善。这表明，模拟DR效应的药物治疗可以改善人类健康。为了找到延长寿命的新化学结构，我们在秀丽隐杆线虫中筛选了30000种合成的、不同的药物样化学物质，并鉴定了几种通过DR机制起作用的结构相关化合物。这些NP中最有效的NP 1通过促进咽部中的谷氨酸信号传导而影响食物感知途径。这导致参与食物感知的GPCR途径被覆盖，该途径通常用于减少谷氨酸信号。我们的研究结果描述了通过药理学掩蔽一种新的感觉通路来激活饮食限制反应，该通路发出食物存在的信号。这表明初级感觉通路可能是人类药理学的新靶点。
Model organisms subject to dietary restriction (DR) generally live longer. Accompanying this lifespan extension are improvements in overall health, based on multiple metrics. This indicates that pharmacological treatments that mimic the effects of DR could improve health in humans. To find new chemical structures that extend lifespan, we screened 30 000 synthetic, diverse drug‐like chemicals in Caenorhabditis elegans and identified several structurally related compounds that acted through DR mechanisms. The most potent of these NP1 impinges upon a food perception pathway by promoting glutamate signaling in the pharynx. This results in the overriding of a GPCR pathway involved in the perception of food and which normally acts to decrease glutamate signals. Our results describe the activation of a dietary restriction response through the pharmacological masking of a novel sensory pathway that signals the presence of food. This suggests that primary sensory pathways may represent novel targets for human pharmacology.
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影响因子：
13.1
作者：
Lucanic, Mark;Lithgow, Gordon J.;Alavez, Silvestre
通讯作者：
Alavez, Silvestre
影响因子：
--
作者：
Fang-Yen, Christopher;Gabel, Christopher V.;Samuel, Aravinthan D. T.;Bargmann, Cornelia I.;Avery, Leon
通讯作者：
Avery, Leon
影响因子：
64.8
作者：
Hendricks, Michael;Ha, Heonick;Maffey, Nicolas;Zhang, Yun
通讯作者：
Zhang, Yun
影响因子：
64.5
作者：
Durieux J;Wolff S;Dillin A
通讯作者：
Dillin A
DOI：
10.1073/pnas.95.22.13091
发表时间：
1998-10-27
影响因子：
11.1
作者：
Lakowski, B;Hekimi, S
通讯作者：
Hekimi, S