2. Academic Validation
  3. Benzimidazole derivative M084 extends the lifespan of Caenorhabditis elegans in a DAF-16/FOXO-dependent way

Benzimidazole derivative M084 extends the lifespan of Caenorhabditis elegans in a DAF-16/FOXO-dependent way

  • Mol Cell Biochem. 2017 Feb;426(1-2):101-109. doi: 10.1007/s11010-016-2884-x.
Ai-Jun Ding 1 2,  Gui-Sheng Wu 1 3,  Bin Tang 3,  Xuechuan Hong 4,  Michael X Zhu 5,  Huai-Rong Luo 6 7
Affiliations

Affiliations

  • 1 State Key Laboratory of Phytochemistry and Plant Resources in West China, Yunnan Key Laboratory of Natural Medicinal Chemistry, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, Yunnan, China.
  • 2 University of Chinese Academy of Sciences, Beijing, 100039, China.
  • 3 School of Pharmacy, Southwest Medical University, Luzhou, 646000, Sichuan, China.
  • 4 Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Wuhan University School of Pharmaceutical Sciences, Wuhan, 430071, Hubei, China.
  • 5 Department of Integrative Biology and Pharmacology, University of Texas Health Science Center at Houston, Houston, TX, 77030, USA.
  • 6 State Key Laboratory of Phytochemistry and Plant Resources in West China, Yunnan Key Laboratory of Natural Medicinal Chemistry, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, Yunnan, China. [email protected].
  • 7 School of Pharmacy, Southwest Medical University, Luzhou, 646000, Sichuan, China. [email protected].
PMID: 27854075 DOI: 10.1007/s11010-016-2884-x
Abstract

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 daf-16, 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.

Keywords

Aging; Benzimidazole derivative M084; Caenorhabditis elegans; Lifespan.

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