Huang Cheng-Wen, Wang Horng-Dar, Bai Hua, Wu Ming-Shiang, Yen Jui-Hung, Tatar Marc, Fu Tsai-Feng, Wang Pei-Yu
Graduate Institute of Brain and Mind Sciences, College of Medicine, National Taiwan University, Taipei, Taiwan. Institute of Biotechnology.
Institute of Biotechnology, Institute of Systems Neuroscience, and Department of Life Science, National Tsing Hua University, HsinChu, Taiwan.
J Gerontol A Biol Sci Med Sci. 2015 Dec;70(12):1461-9. doi: 10.1093/gerona/glv094. Epub 2015 Aug 11.
The aging process is a universal phenomenon shared by all living organisms. The identification of longevity genes is important in that the study of these genes is likely to yield significant insights into human senescence. In this study, we have identified Tequila as a novel candidate gene involved in the regulation of longevity in Drosophila melanogaster. We have found that a hypomorphic mutation of Tequila (Teq(f01792)), as well as cell-specific downregulation of Tequila in insulin-producing neurons of the fly, significantly extends life span. Tequila deficiency-induced life-span extension is likely to be associated with reduced insulin-like signaling, because Tequila mutant flies display several common phenotypes of insulin dysregulation, including reduced circulating Drosophila insulin-like peptide 2 (Dilp2), reduced Akt phosphorylation, reduced body size, and altered glucose homeostasis. These observations suggest that Tequila may confer life-span extension by acting as a modulator of Drosophila insulin-like signaling.
衰老过程是所有生物共有的普遍现象。长寿基因的鉴定很重要,因为对这些基因的研究可能会对人类衰老产生重要见解。在本研究中,我们已将龙舌兰(Tequila)鉴定为参与调控黑腹果蝇寿命的一个新候选基因。我们发现,龙舌兰的一个亚效突变(Teq(f01792))以及果蝇胰岛素生成神经元中龙舌兰的细胞特异性下调,均能显著延长寿命。龙舌兰缺失诱导的寿命延长可能与胰岛素样信号传导减少有关,因为龙舌兰突变果蝇表现出胰岛素调节异常的几种常见表型,包括循环中的果蝇胰岛素样肽2(Dilp2)减少、Akt磷酸化减少、体型减小以及葡萄糖稳态改变。这些观察结果表明,龙舌兰可能通过作为果蝇胰岛素样信号传导的调节剂来延长寿命。