The role of neural signaling pathways in costs of reproduction on aging

项目摘要 健康权衡被认为在健康特征的遗传结构中起着基础性的作用，包括 塑造与人类健康相关的基因。生殖成本，特别是那些影响寿命和 晚年疾病，已经在表型和群体遗传水平上进行了广泛的探索 但人们对其潜在的生物学机制知之甚少。在我们对果蝇的研究中， 我们发现，繁殖的生存成本是由进化调节的 保守的神经肽，这些肽由神经回路动态控制，影响 生殖成功，这些回路影响下游代谢网络。我们的目标是 拟议的研究是为了识别和表征协调 控制繁殖成本并影响其演变。我们提出一个模型，在这个模型中，个人的 生殖策略及其对衰老的影响是由神经反应决定的 与该个体的生育期望和生育成就相结合。重要的是 这些决定独立于与交配本身相关的任何身体或能量影响。我们将测试 该模型使用创新的方法来识别环境线索和潜在的感知系统 生殖期望和奖励，以及受这些过程影响的信号通路。 我们将结合简化论的方法，使用单基因突变和先进的细胞生物学技术 对于神经操纵，用系统和网络生物学的方法来确定潜在的机制 生殖和衰老。完成后，这项研究将为预兆的线索提供新的见解 生殖成功、这些线索被解释的机制以及它们的调控效应 按寿命计算。这些见解将有助于我们对典型的进化和健康问题的理解- 包括性冲突、生殖投资和老龄化。

Project Summary Fitness trade-offs are thought to play a fundamental role in the genetic architecture of fitness traits, including shaping genes relevant to human health. Reproductive costs, particularly those that influence lifespan and late-age disease, have been explored at the phenotypic and population genetic levels in a wide range of species, but little is known about their underlying biological mechanisms. In our work on the fruit fly, Drosophila melanogaster, we have found that survival costs of reproduction are mediated by evolutionarily conserved neuropeptides, that these peptides are dynamically controlled by neural circuits that influence reproductive success, and that these circuits influence downstream metabolic networks. The goal of our proposed research is to identify and characterize conserved neural signaling pathways that orchestrate the control of costs of reproduction and influence their evolution. We propose a model whereby an individual’s reproductive strategy, with its attendant effects on aging, is determined by neurological decisions in response to a combination of that individual’s reproductive expectation and reproductive achievement. Importantly, these decisions are independent of any physical or energetic effects associated with mating itself. We will test this model using innovative approaches to identify the environmental cues and perceptive systems underlying reproductive expectation and reward, as well as the signaling pathways that are influenced by these processes. We will combine a reductionist approach, using single-gene mutations and advanced cell-biology techniques for neuronal manipulations, with a systems and network biology approach to identify mechanisms underlying reproduction and aging. When complete, this research will provide new insights into the cues that portend reproductive success, the mechanisms through which those cues are interpreted, and their regulatory effects on lifespan. These insights will aid our understanding of quintessential evolutionary and health issues – including sexual conflict, reproductive investment, and aging.