Longevity and reproduction in Drosophila

描述（由申请人提供）：随着美国人口寿命的增加，越来越多的妇女选择要求高的职业，推迟生育到以后几年，与年龄有关的健康问题成为全国关注的问题。迫切需要了解衰老过程的生物学基础和人类生殖衰老的基础。对果蝇等模式生物的研究有助于揭示几个寿命调节基因;然而，推迟衰老的遗传途径还远未完全了解。我们最近发现，基因周期（per），一个众所周知的组成部分的生物钟，影响寿命和生育能力的雌性果蝇。 人们对这种基因及其蛋白质产物有着广泛的了解;因此，可以使用工具来研究它在衰老中的作用。我们计划验证和扩大我们的初步发现，并解决几个新的问题：1）每对寿命的影响是性别特异性的吗？2)是否每影响生殖和寿命在处女和交配的女性？3)每个动作都涉及哪些生理系统？这些研究的结果将首次深入了解时钟基因周期在所研究表型中的作用机制，并使我们能够开发一项研究项目资助（R01），旨在了解支撑女性生殖衰老的分子途径。我们的目标与NIA计划一致，即加速发现其他长寿相关基因并表征其生物学功能。考虑到从苍蝇到人类的生物计时中PER的保守功能，关于该基因的作用机制的知识可能为我们理解人类的生殖和时间老化提供重要贡献。

DESCRIPTION (provided by applicant): As life span increases in the US population and more women choose demanding careers deferring childbearing to later years, age-related health problems become a matter of national concern. There is an urgent need to understand the biological basis of the aging process and the basis of reproductive senescence in humans. Research on model organisms such as Drosophila helped to uncover several lifespan-regulating genes; however, genetic pathways that postpone aging are far from being fully understood. We recently discovered that the gene period (per), a well-known component of the biological clock, affects longevity and fertility in female Drosophila. There is extensive knowledge of this gene and its protein product; therefore, tools are available to research its role in aging. We plan to verify and expand our initial findings and address several new questions: 1) Are per effects on lifespan gender-specific? 2) Does per affect reproduction and life span in both virgin and mated females? 3) Which physiological systems are involved in per action? Results of these proposed studies will provide the first insights into the mechanisms underlying the action of the clock gene period in the investigated phenotype and allow us to develop a research project grant (R01) aimed at understanding the molecular pathways underpinning female reproductive aging. Our goal is consistent with NIA plans to accelerate efforts to discover additional longevity-related genes and to characterize their biological function. Given the conserved functions of per in biological timing from flies to humans, knowledge gained concerning the mechanism of action of this gene may provide important contributions to our understanding of reproductive and chronological aging in humans.