DROSOPHILA LONGEVITY ASSURANCE GENES

这个项目的长期目标是识别直接 会影响果蝇的寿命，并最终影响哺乳动物的寿命。这个 果蝇这种功能的候选基因是热休克基因，以及 一些其他已被发现存在差异的基因 在衰老过程中在转录水平上表达。任何与 它们的长寿表达将通过检测RNA水平来确定 在基因选择推迟的果蝇品系中 老化(“O”株)及其对照(“B”株)。在…中扮演直接角色 然后将通过实验增加和增加 降低转基因果蝇中基因的表达。这些 实验将涉及开发用于过度表达的新载体 候选人的表现滞后，以及表现出延缓衰老的股票的创建 它们与转基因技术兼容。最后，任何哺乳动物 果蝇LAGS的同源物将被识别出来。具体目标是： 1.分析热休克基因在现有O&B菌株中的表达。 2.分析附加克隆候选滞后在现有O&中的表达 B株。 3.培育出标记为O和B的ry506和w1118菌株：O[ry]和B[ry]，以及Ow& BW. 4.创建和测试新的可诱导-过表达转化载体， 并在果蝇品系中过表达候选滞后基因，以分析其影响 关于长寿。 5.果蝇品系中的低表达候选滞后，并分析 长寿。 6.引入精选的转换构造，并使用 特定于年龄的表达模式，变成新标记的O[ry]和B[ry] 菌株。 7.鉴定和克隆果蝇的啮齿动物和人类同源基因。

The long term goals of this project are to identify genes which directly affect the longevity of Drosophila, and ultimately, mammals. The candidates for this function in Drosophila are the heat shock genes, and a number of other genes which have been found to be differentially expressed at the transcriptional level during aging. Any correlation of their expression with longevity will be determined by examining RNA levels in strains of flies which have been genetically selected for postponed aging ("O" strains), and their controls ("B" strains). A direct role in regulating longevity will then be assayed by experimentally increasing and decreasing the expression of the genes in transgenic flies. These experiments will involve the development of new vectors for overexpression of candidate LAGs, and the creation of stocks exhibiting postponed aging which are compatible with transgenic technologies. Finally, any mammalian homologs of Drosophila LAGs will be identified. The specific aims are: 1. Analyze heat shock gene RNA expression in existing O & B strains. 2. Analyze expression of additional cloned candidate LAGs in existing O & B strains. 3. Create ry506 and w1118 marked O and B strains: O[ry] & B[ry], and Ow & Bw. 4. Create and test new inducible-overexpression transformation vectors, and overexpress candidate LAGs in Drosophila strains, to analyze effects on longevity. 5. Underexpress candidate LAGs in Drosophila strains, and analyze longevity. 6. Introduce selected transformation constructs, and enhancer-traps with aging-specific expression patterns, into new marked O[ry] and B[ry] strains. 7. Identify and clone rodent and human homologs of Drosophila LAGs.