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题名: Benzimidazole derivative M084 extends the lifespan of Caenorhabditis elegans in a DAF-16/FOXO-dependent way
作者: Ding, Ai-Jun1, 2; Wu, Gui-Sheng1, 3; Tang, Bin3; Hong, Xuechuan4; Zhu, Michael X.5; Luo, Huai-Rong1, 3
刊名: MOLECULAR AND CELLULAR BIOCHEMISTRY
关键词: Aging ; Benzimidazole derivative M084 ; Caenorhabditis elegans ; Lifespan
英文摘要: With the growth of aging population, there is increasing demand to develop strategy to improve the aging process and aging-related diseases. Benzimidazole and its derivatives are crucial heterocyclic backbone of many drugs and compounds with diverse therapeutic applications, including alleviation of aging-related diseases. Here, we investigate if the benzimidazole derivative n-butyl-[1H]-benzimidazol-2-amine (M084), a novel inhibitor of TRPC4 and TRPC5 channels and antidepressant, could affect the lifespan of Caenorhabditis elegans (C. elegans). Our results showed that M084 could extend the lifespan of C. elegans, delay age-related decline of phenotypes, and improve stress resistance. M084 could not extend the lifespan of the loss-of-function mutants of daf16, daf-2, pdk-1, aak-2, clk-1, isp-1, sir-2.1, and skn-1. M084 could decrease the ATP level and increase the gene expression of mitochondrial unfolded protein response factors. Thus, M084 might inhibit the mitochondrial respiration, activate mitochondrial unfolded protein response and AMPK, recruite SIR-2.1 and SKN-1, and finally through the transcription factor DAF-16, delay the aging process of C. elegans. Our findings reveal the new pharmaceutical potential of benzimidazole derivatives and provide clue for developing novel anti-aging agents.
出版日期: 2017-02-01
卷号: 426, 期号:1-2, 页码:101-109
语种: 英语
收录类别: SCI
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.kib.ac.cn/handle/151853/51014
Appears in Collections:植物化学与西部植物资源持续利用国家重点实验室_期刊论文

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作者单位: 1.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Yunnan Key Lab Nat Med Chem, Kunming 650201, Yunnan, Peoples R China
2.Univ Chinese Acad Sci, Beijing 100039, Peoples R China
3.Southwest Med Univ, Sch Pharm, Luzhou 646000, Sichuan, Peoples R China
4.Wuhan Univ, Key Lab Combinatorial Biosynth & Drug Discovery, Sch Pharmaceut Sci, Wuhan 430071, Hubei, Peoples R China
5.Univ Texas Hlth Sci Ctr Houston, Dept Integrat Biol & Pharmacol, Houston, TX 77030 USA

Recommended Citation:
Ding, Ai-Jun,Wu, Gui-Sheng,Tang, Bin,et al. Benzimidazole derivative M084 extends the lifespan of Caenorhabditis elegans in a DAF-16/FOXO-dependent way[J]. MOLECULAR AND CELLULAR BIOCHEMISTRY,2017,426(1-2):101-109.
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