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

神经信号通路在衰老繁殖成本中的作用

基本信息

批准号：
9902308
负责人：
SCOTT PLETCHER
金额：
$ 38.63万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-04-01 至 2024-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9902308
关键词：
Achievement Age Aging Amino Acid Transporter Animals Biochemical Pathway Biological Biological Process Biology Brain Cellular biology Cholecystokinin Conflict (Psychology)Copulation Cost Control Courtship Cues Data Disease Drosophila genus Drosophila melanogaster Equilibrium Evolution Family Fatty acid glycerol esters Female Future Gene Mutation Genes Genetic Genetic study Goals Gonadotropin Hormone Releasing Hormone Health Human Immune Individual Influentials Ingestion Intake Investments Longevity Mediating Modeling Motivation Neurologic Neurons Neuropeptides Neurotransmitters Nutrient Outcome Output Partner in relationship Pathway interactions Peptides Perception Phenotype Pheromone Physiological Play Population Genetics Process Production Proteins Reagent Reproduction Research Resistance Resources Rewards Role Sensory Serotonin Serotonin Receptor 5-HT2A Shapes Signal Pathway Signal Transduction Site Stress Structure System Techniques Technology Testing Variant Work cost egg expectation experience fitness fly genetic architecture innovation insight life history male metabolome neural circuit neuromechanism neurotransmission novel receptor reproductive reproductive success response reward circuitry sex solute tool trait

项目摘要

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.

项目概要健康权衡被认为在健康特征的遗传结构中发挥着重要作用，包括塑造与人类健康相关的基因，特别是那些影响寿命和寿命的基因。晚年疾病，已在广泛的表型和群体遗传水平上进行了探索但在我们对果蝇的研究中，人们对其潜在的生物学机制知之甚少。果蝇，我们发现繁殖的生存成本是由进化介导的保守的神经肽，这些肽由影响神经回路的动态控制生殖成功，以及这些回路影响下游代谢网络是我们的目标。拟议的研究是识别和表征保守的神经信号通路，这些通路协调我们提出了一个模型，通过该模型可以控制繁殖成本并影响其进化。生殖策略及其对衰老的附带影响是由神经系统的反应决定的重要的是，该人的生殖期望和生殖成就的结合。这些决定独立于与交配本身相关的任何身体或能量影响。我们将进行测试。该模型使用创新方法来识别环境线索和底层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。我们将结合还原论方法，使用单基因突变和先进的细胞生物学技术用于神经操作，采用系统和网络生物学方法来识别潜在机制完成后，这项研究将为预示的线索提供新的见解。生殖成功、解释这些线索的机制及其调节作用这些见解将有助于我们理解典型的进化和健康问题—— 包括性冲突、生殖投资和老龄化。