Longevity and reproduction in Drosophila

描述(由申请人提供)：随着美国人口寿命的延长和越来越多的女性选择要求苛刻的职业推迟生育，与年龄相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帮助发现了几个调节寿命的基因；然而，延缓衰老的遗传途径远未被完全了解。我们最近发现，基因周期(PER)是生物钟的一个众所周知的组成部分，它影响雌性果蝇的寿命和生育能力。 人们对该基因及其蛋白质产物有广泛的了解；因此，可以使用工具来研究它在衰老中的作用。我们计划验证和扩展我们的初步发现，并解决几个新问题：1)PER对寿命的影响是否因性别而异？2)PER是否影响处女和交配雌性的生殖和寿命？3)PER涉及哪些生理系统？这些拟议研究的结果将首次深入了解时钟基因周期在所研究的表型中的作用机制，并使我们能够开发一个旨在了解支持女性生殖衰老的分子途径的研究项目拨款(R01)。我们的目标与NIA加快发现更多与长寿相关的基因并确定其生物学功能的计划是一致的。鉴于PER在从苍蝇到人类的生物计时中具有保守的功能，有关该基因作用机制的知识可能会为我们理解人类的生殖和时间衰老提供重要贡献。

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.