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选择性抗癌剂可抑制果蝇衰老。

Selective anticancer agents suppress aging in Drosophila.

作者信息

Danilov Anton, Shaposhnikov Mikhail, Plyusnina Ekaterina, Kogan Valeria, Fedichev Peter, Moskalev Alexey

机构信息

Institute of Biology, Komi Science Center, Russian Academy of Sciences, Syktyvkar, 167982, Russia.

出版信息

Oncotarget. 2013 Sep;4(9):1507-26. doi: 10.18632/oncotarget.1272.

Abstract

Mutations of the PI3K, TOR, iNOS, and NF-κB genes increase lifespan of model organisms and reduce the risk of some aging-associated diseases. We studied the effects of inhibitors of PI3K (wortmannin), TOR (rapamycin), iNOS (1400W), NF-κB (pyrrolidin dithiocarbamate and QNZ), and the combined effects of inhibitors: PI3K (wortmannin) and TOR (rapamycin), NF-κB (pyrrolidin dithiocarbamates) and PI3K (wortmannin), NF-κB (pyrrolidine dithiocarbamates) and TOR (rapamycin) on Drosophila melanogaster lifespan and quality of life (locomotor activity and fertility). Our data demonstrate that pharmacological inhibition of PI3K, TOR, NF-κB, and iNOS increases lifespan of Drosophila without decreasing quality of life. The greatest lifespan expanding effect was achieved by a combination of rapamycin (5 μM) and wortmannin (5 μM) (by 23.4%). The bioinformatic analysis (KEGG, REACTOME.PATH, DOLite, and GO.BP) showed the greatest aging-suppressor activity of rapamycin, consistent with experimental data.

摘要

PI3K、TOR、iNOS和NF-κB基因的突变可延长模式生物的寿命,并降低一些与衰老相关疾病的风险。我们研究了PI3K抑制剂(渥曼青霉素)、TOR抑制剂(雷帕霉素)、iNOS抑制剂(1400W)、NF-κB抑制剂(吡咯烷二硫代氨基甲酸盐和QNZ)的作用,以及抑制剂的联合作用:PI3K(渥曼青霉素)和TOR(雷帕霉素)、NF-κB(吡咯烷二硫代氨基甲酸盐)和PI3K(渥曼青霉素)、NF-κB(吡咯烷二硫代氨基甲酸盐)和TOR(雷帕霉素)对黑腹果蝇寿命和生活质量(运动活性和繁殖力)的影响。我们的数据表明,对PI3K、TOR、NF-κB和iNOS进行药理学抑制可延长果蝇寿命,且不降低生活质量。雷帕霉素(5 μM)和渥曼青霉素(5 μM)联合使用时实现了最大的寿命延长效果(延长了23.4%)。生物信息学分析(KEGG、REACTOME.PATH、DOLite和GO.BP)显示雷帕霉素具有最大的衰老抑制活性,这与实验数据一致。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6831/3824538/276e406f672c/oncotarget-04-1507-g001.jpg

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