視網膜退化B基因(rdgB)在果蠅的光訊號傳導中扮演重要的角色。它在磷脂酸肌醇循環(PI cycle)中負責運送磷脂酸肌醇(PI)。我們實驗室在之前的研究中發現降低另一個同樣參與磷脂酸肌醇循環的視網膜退化A基因 (rdgA)基因的表現量會延長果蠅的壽命。然而，rdgB是否也會在壽命的調控中扮演著某些角色目前依然是未知的。在這一篇論文當中，我們發現rdgB的突變株rdgBB27337 和 rdgBEP1520 顯示出延長的壽命。在神經中降低rdgB的表現量同樣會使得壽命增加。但是在肌肉中降低rdgB的表現量卻會使得壽命減少。藉由西方墨點法，我們發現rdgBB27337 和 rdgBEP1520 的磷酸化S6激酶(P-S6K)的量會下降。除此之外，餵食雷帕黴素標靶蛋白質(Target of rapamycin, TOR)的抑制劑雷帕黴素(rapamycin)並不會使rdgBB27337 和 rdgBEP1520延長的壽命更進一步地增加。這些結果顯示了降低rdgB的表現量是透過減弱雷帕黴素標靶蛋白質訊號傳遞路徑而延長壽命。此外，rdgBB27337 和 rdgBEP1520 也顯示出了減緩的爬行能力年老衰退與增強的氧化壓力抗性。總合來說，這些數據顯示了在神經中減少rdgB的表現量會使得果蠅的壽命及健康時限延長。

retinal degeneration B (rdgB) plays an important role in Drosophila phototransduction. It functions as phosphatidylinositol (PI) transporter in PI cycle. We pervious found that knockdown of retinal degeneration A (rdgA), also a gene in PI cycle, extends lifespan in Drosophila. Whether rdgB can also play a role in lifespan regulation remains unknown. Here, we report rdgB mutant lines, rdgBB27337 and rdgBEP1520, exhibit lifespan extension. Knockdown of rdgB in neuron also able to extend lifespan. However, knockdown of rdgB in muscle exhibits shortened lifespan. Western blotting data showed p-S6K levels were reduced in rdgBB27337 and rdgBEP1520. Furthermore, the treatment of TOR inhibitor rapamycin does not further enhance the extended lifespan of rdgBB27337 and rdgBEP1520. These data suggest that reduced rdgB expression increases lifespan via reducing TOR signaling. Moreover, rdgBB27337 and rdgBEP1520 also attenuate the climbing ability decline with age and enhance oxidative stress tolerance. Together, these data indicate that reduced rdgB expression in neuron augments lifespan and healthspan in Drosophila.

Abstract ii
中文摘要 ii
致謝 iii
Introduction 3
Materials and methods 7
Fly strains and maintenance 7
Lifespan survival assay 7
Oxidative stress test 7
Starvation stress test 7
Climbing ability assay 8
RNA extraction and Reverse transcription 8
Real-time PCR (Q-PCR) 9
Western blots 9
Results 10
rdgBB27337 and rdgBEP1520 mutants exhibit lifespan extension 10
Knockdown of rdgB in neurons extends lifespan in Drosophila 10
rdgBB27337 and rdgBEP1520 show better oxidative stress tolerance than control 11
RNAi knockdown of rdgB ubiquitously or in neuron or muscle does not display better oxidative stress tolerance 12
rdgB mutants do not exhibit better starvation tolerance 13
Knockdown of rdgB in neuron and eye display starvation tolerance enhancement in male 13
rdgBB27337 and rdgBEP1520 attenuate the decline of climbing ability with age 14
Knockdown of rdgB in neuron attenuates the decline of climbing ability with age 14
Mutations of rdgB extend lifespan via TOR signaling 15
Discussion 16
Figures 19
Tables 43
Appendix 57
References 60

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