Department of Biomedical Sciences, University of South Alabama, HAHN 4025, 5721 USA Drive N, Mobile, AL 36688.
J Gerontol A Biol Sci Med Sci. 2013 Oct;68(10):1157-69. doi: 10.1093/gerona/glt031. Epub 2013 Jun 1.
The hypothesis tested in this study was that single-gene mutations found previously to extend the life span of Drosophila melanogaster could do so consistently in both long-lived y w and standard w (1118) genetic backgrounds. GAL4 drivers were used to express upstream activation sequence (UAS)-responder transgenes globally or in the nervous system. Transgenes associated with oxidative damage prevention (UAS-hSOD1 and UAS-GCLc) or removal (EP-UAS-Atg8a and UAS-dTOR (FRB) ) failed to increase mean life spans in any expression pattern in either genetic background. Flies containing a UAS-EGFP-bMSRA (C) transgene associated with protein repair were found not to exhibit life extension or detectable enhanced green fluorescent protein (EGFP) activity. The presence of UAS-responder transgenes was confirmed by PCR amplification and sequencing at the 5' and 3' end of each insertion. These results cast doubt on the robustness of life extension in flies carrying single-gene mutations and suggest that the effects of all such mutations should be tested independently in multiple genetic backgrounds and laboratory environments.
本研究旨在验证先前发现的可延长黑腹果蝇寿命的单基因突变是否能在长寿命 yw 和标准 w(1118)遗传背景下持续发挥作用。我们使用 GAL4 驱动子在全身或神经系统中表达上游激活序列 (UAS)-应答转基因。与氧化损伤预防(UAS-hSOD1 和 UAS-GCLc)或清除(EP-UAS-Atg8a 和 UAS-dTOR(FRB))相关的转基因未能在两种遗传背景下的任何表达模式中增加平均寿命。与蛋白质修复相关的 UAS-EGFP-bMSRA(C)转基因的存在并未表现出寿命延长或可检测到增强型绿色荧光蛋白 (EGFP)活性。通过聚合酶链式反应 (PCR) 扩增和插入物 5' 和 3' 端的测序确认了 UAS-应答转基因的存在。这些结果对携带单基因突变的果蝇寿命延长的稳健性提出了质疑,并表明所有这些突变的影响都应在多个遗传背景和实验室环境中独立进行测试。