Department of Physiology, College of Medicine, Korea University, 126-1 Anam-Dong 5 Ga, Seongbuk-Gu, Seoul 136-705, Republic of Korea.
Mech Ageing Dev. 2012 May;133(5):234-45. doi: 10.1016/j.mad.2012.02.001. Epub 2012 Feb 24.
In an initial preliminary screen we identified factors associated with controlling Drosophila aging by examining longevity in adults where EP elements induced over-expression or antisense-RNA at genes adjacent to each insertion. Here, we study 45 EP lines that initially showed at least 10% longer mean lifespan than controls. These 45 lines and a daughterless (da)-Gal4 stock were isogenized into a CS10 wild-type background. Sixteen EP lines corresponding to 15 genes significantly extended lifespan when their target genes were driven by da-Gal4. In each case, the target genes were seen to be over-expressed. Independently derived UAS-gene transgenic stocks were available or made for two candidates: ImpL2 which is ecdysone-inducible gene L2, and CG33138, 1,4-alpha-glucan branching enzyme. With both, adult lifespan was increased upon over-expression via the GeneSwitch inducible Gal4 driver system. Several genes in this set of 15 correspond to previously discovered longevity assurance systems such as insulin/IGF-1 signaling, gene silencing, and autophagy; others suggest new potential mechanisms for the control of aging including mRNA synthesis and maturation, intracellular vesicle trafficking, and neuroendocrine regulation.
在初步的初步筛选中，我们通过检查邻近每个插入点的基因的 EP 元件过表达或反义 RNA 诱导的成年期寿命，来确定与控制果蝇衰老相关的因素。在这里，我们研究了 45 条 EP 线，这些线最初显示的平均寿命比对照至少长 10%。这 45 条线和无女儿基因（da）-Gal4 库存被同化为 CS10 野生型背景。当它们的靶基因被 da-Gal4 驱动时，16 条 EP 线对应 15 个基因显著延长了寿命。在每种情况下，靶基因都被观察到过表达。两个候选基因（ImpL2，即蜕皮激素诱导基因 L2 和 CG33138，1,4-α-葡聚糖分支酶）都有独立衍生的 UAS-基因转基因株系。通过基因开关诱导的 Gal4 驱动系统的过表达，两种基因的成年期寿命都增加了。这 15 个基因中的几个与先前发现的长寿保证系统相对应，如胰岛素/IGF-1 信号、基因沉默和自噬；其他基因则表明了控制衰老的新的潜在机制，包括 mRNA 合成和成熟、细胞内囊泡运输和神经内分泌调节。
