Systems and methods for molecular dissection of socio-environmental effects on aging

社会环境对衰老影响的分子剖析系统和方法

• 批准号: 10511422
• 负责人: SCOTT PLETCHER
• 金额: $ 32.56万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10511422
• 关键词: Acute; Affect; Afferent Neurons; Age; Aging; Animal Behavior; Animals; Assessment tool; Behavior; Behavior Control; Behavior monitoring; Behavioral; Biogenic Amines; Biological; Biological Markers; Biological Models; Cognitive aging; Computer software; Coupled; Data Analyses; Diet; Dissection; Drosophila genus; Drosophila melanogaster; Ensure; Environment; Environmental Exposure; Environmental Risk Factor; Exhibits; Exposure to; Fatty acid glycerol esters; Food; Foundations; Frequencies; Future; Gene Expression; Genes; Genetic; Goals; Health; Human; Individual; Influentials; Intervention; Investigation; Knowledge; Laboratories; Life; Light; Link; Long-Term Effects; Longevity; Longitudinal Studies; Measurement; Measures; Mediating; Methods; Molecular; Motivation; Movement; Neurologic; Neurons; Neuropeptides; Nutrient; Organism; Pathway interactions; Pattern; Phase; Physiological; Research; Resistance; Rewards; Scientist; Series; Shapes; Social Behavior; Social Conditions; Social Environment; Social Interaction; Stress; Structure; System; Technology; Temperature; Testing; Time; Uncertainty; Work; adverse outcome; age related; base; design; dietary restriction; experience; feeding; fly; genetic manipulation; healthy aging; high dimensionality; innovation; invention; lipid metabolism; metabolome; metabolomics; middle age; mortality; multidimensional data; neural circuit; neurotransmission; new technology; programs; resilience; response; sex; sleep pattern; social; social factors; tool; treatment group

Project Summary Despite extensive research on the relationship between early-life social and physical environmental exposures, and consequent effects on aging, little is understood about the mechanisms that link social interactions and aging. The work proposed here provides technological, conceptual, and analytical innovations to fill this gap. The R61 phase of our proposal will build on our existing technologies, which precisely measure how groups of the fruit fly, Drosophila melanogaster, interact with each other as well as with their surroundings, to accommodate long-term, longitudinal studies of aging individuals. Key components of our system will include: (i) our DTrack video tracking system, which provides detailed and near-continuous quantification of changes in movement, exploration, and social interactions, and (ii) our FLIC system, which measures each fly’s interactions with food every 50ms and allows us to analyze the fine structure of feeding activities in real time. These behavioral monitoring systems will interface with external Smart control modules that provide programmable open- and closed-loop control of environmental variables, such as temperature and light, and that will be coupled to genetic systems for acute manipulation of gene expression and neuron activity in response to specific behaviors. During the R61 phase, we will also develop experimental and statistical tools to analyze high-dimensional -omic profiles, which will be used to identify molecular mechanisms that shape and are shaped by social interactions and aging. A series of Goals and Milestones will ensure that this new technology supports the requirements for long term husbandry and that it is robust, reliable, and effective for detecting reasonable differences in behavioral profiles among individuals and groups of individuals. The R33 component of our proposal will use these tools to provide the first detailed characterization of age-dependent socio-environment interactions in an influential model system for aging research, and we will evaluate their association with mechanisms of slowed aging. Importantly, our research will also begin dissecting the mechanisms underlying how aging modulates social interactions and how these interactions modulate aging. We will accomplish this by exploiting our ability to dynamically stimulate and inhibit individual neurons in live, behaving animals to identify the molecular mechanisms through which behavioral interactions influence lifespan and to evaluate behavioral and molecular interventions that reverse the deleterious consequences of adverse social conditions. Measures of resilience in metabolome profiles will enable us to link relationships between social interactions and aging to specific functional cellular pathways. The technology and experimental paradigms that we develop will push the limits of behavioral monitoring and analysis in any organism, will offer the first glimpses of mechanisms through which behavioral interactions influence aging in Drosophila, and will provide a foundation for future investigation in other species, including humans.

项目概要 尽管对生命早期的社会和物理环境暴露之间的关系进行了广泛的研究， 以及随之而来的对衰老的影响，人们对将社会互动与衰老联系起来的机制知之甚少。 这里提出的工作提供了技术、概念和分析创新来填补这一空白。 我们提案的 R61 阶段将建立在我们现有技术的基础上，这些技术精确测量群体如何 果蝇（Drosophila melanogaster）与彼此以及与周围环境相互作用， 我们系统的关键组成部分将适应对老龄化个体的长期纵向研究。 包括：(i) 我们的 DTrack 视频跟踪系统，它提供详细且近乎连续的量化 运动、探索和社交互动的变化，以及 (ii) 我们的 FLIC 系统，该系统测量每只苍蝇的 每 50 毫秒与食物进行一次交互，使我们能够实时分析进食活动的精细结构。 这些行为监控系统将与外部智能控制模块接口，提供 环境变量的可编程开环和闭环控制，例如温度和光照，以及 它将与遗传系统耦合，用于急性操纵基因表达和神经元活动 在R61阶段，我们还将开发实验和统计工具来响应特定行为。 分析高维组学概况，这将用于识别塑造和 由社会互动和老龄化塑造的一系列目标和里程碑将确保这一新目标。 技术支持长期饲养的要求，并且它是稳健、可靠和有效的 检测个体和个体群体之间行为特征的合理差异。 我们提案的一部分将使用这些工具来提供年龄依赖性的第一个详细特征 社会环境相互作用在一个有影响力的衰老研究模型系统中，我们将评估它们 重要的是，我们的研究也将开始剖析与延缓衰老的机制。 衰老如何调节社会互动以及这些互动如何调节衰老的潜在机制。 我们将通过利用我们动态刺激和抑制单个神经元的能力来实现这一目标 活的、有行为的动物来识别行为相互作用影响的分子机制 寿命并评估可逆转有害后果的行为和分子干预措施 代谢组谱中的逆境恢复力测量将使我们能够将关系联系起来。 社会互动和衰老与特定功能细胞途径之间的关系。 我们将开发的实验范式将突破任何领域行为监测和分析的极限 有机体，将首次揭示行为相互作用影响衰老的机制 果蝇，并将为未来对包括人类在内的其他物种的研究奠定基础。