Deterministic and stochastic effects of diet on demography

饮食对人口统计学的确定性和随机影响

• 批准号: 8815705
• 负责人: Patrick C. Phillips
• 金额: $ 31.97万
• 依托单位: UNIVERSITY OF OREGON
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-05-01 至 2020-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8815705
• 关键词: Address; Affect; Aging; Animals; Bacteria; Biological Assay; Biological Models; Caenorhabditis elegans; Caloric Restriction; Complex; Custom; Data; Data Analyses; Demographic Analyses; Demography; Development; Diet; Diet and Nutrition; Disease; Equilibrium; Exposure to; Food; Food deprivation (experimental); Gene Expression; Genes; Genetic; Growth and Development function; Health; Health Status; Human; Incidence; Individual; Individual Differences; Insulin Signaling Pathway; Intervention; Life; Life Cycle Stages; Longevity; Measures; Mediating; Metabolic; Methodology; Microfluidic Microchips; Microfluidics; Modeling; Molecular; Mutation; Nature; Nematoda; Neurons; Nutritional; Outcome; Oviposition; Pathway interactions; Pattern; Perception; Physiologic pulse; Physiological; Play; Population; Probability; Process; Property; Quality of life; Relative (related person); Reproduction; Resistance; Resources; Risk Factors; Role; Sensory; Smell Perception; Sorting - Cell Movement; Source; Stress; Structure; System; Taste Perception; Testing; Time; Variant; Work; age related; base; biological adaptation to stress; biological systems; density; design; dietary restriction; egg; genetic manipulation; innovation; insight; insulin signaling; mutant; novel; nutrition; overexpression; public health relevance; reproductive; response; sensory input; tool

DESCRIPTION (provided by applicant): Diet plays a critical role in many health outcomes, from incidence of disease to quality of life to longevity itself. Most of the biological systems known to be influenced by diet and nutrition are involved in mediating the balance between growth, development, reproduction, and the response to stress. Dietary treatments, such as caloric restriction, and certain mutations, such as those involved in the insulin signaling pathway, are known to increase lifespan yet frequently yield negative effects on reproduction. The precise demographic consequences of these interventions are largely unknown, however. How any given individual will respond to a particular dietary regime depends on a complex combination of genetics, random environmental differences, and the systematic effects of the diet itself, leading to complex stochastic life trajectories for each individual. Understanding the functional basis of this complexity requires estimates of the demographic trajectories of numerous genetically identical individuals so that the entire distribution individual outcomes can be characterized and also requires a statistical framework that allows for the accumulation of individual differences to be attributed to the inherent properties-the stochastic kernel-of that individual. The model nematode Caenorhabditis elegans is especially amenable to addressing these problems because it has become a central player in understanding the genetic and physiological bases of stress response and aging and because it can be used to generated large numbers of genetically identical individuals for demographic analysis. Here, we propose: (1) to utilize innovative microfluidic and statistical approaches to precisely characterize individual demographic trajectories under different dietary inputs, (2) to examine the role of developmental state and insulin signaling and stress response pathways in mediating variation in reproductive patterns in the face of dietary fluctuations, and (3) to characterize the role of perception in dietary modulation of reproductive patterning. We will use custom designed microfluidic systems that (1) provide automated characterization of the reproductive dynamics of tens of thousands of individuals, (2) allow precise control of diet and food level, and (3) enable sorting of individuals based on physiological state, such levels of gene expression. A novel framework based on stochastic demography will be used to analyze the data in order to estimate individual stochastic kernels for natural isolates and longevity-related mutants reared under conditions of dietary restriction and exposure to naturally occurring nematode-associated bacteria. Perception deficient mutants will be used to distinguish modulation of reproduction driven by sensory input versus metabolic state. Taken together, this work will provide novel and comprehensive approaches for studying stochastic demography within this important model system and will provide insights into how the impact of treatments leading to increased longevity propagate throughout the reproductive lifespan of an individual.

描述（由申请人提供）：饮食在许多健康结果中起着关键作用，从疾病的发生率到生活质量再到寿命本身。大多数已知受饮食和营养影响的生物系统都参与调节生长，发育，繁殖和对压力的反应之间的平衡。饮食治疗，如热量限制和某些突变，如参与胰岛素信号通路的突变，已知可以延长寿命，但经常对生殖产生负面影响。然而，这些干预措施的确切人口后果在很大程度上是未知的。任何一个特定的个体对特定饮食制度的反应取决于遗传学、随机环境差异和饮食本身的系统性影响的复杂组合，从而导致每个个体复杂的随机生命轨迹。了解 这种复杂性的功能基础需要估计许多遗传相同的个体的人口轨迹，以便可以表征整个分布个体结果，并且还需要允许将个体差异的累积归因于该个体的固有属性（随机核）的统计框架。模式线虫秀丽隐杆线虫特别适合解决这些问题，因为它已成为理解应激反应和衰老的遗传和生理基础的核心参与者，并且因为它可用于产生大量遗传相同的个体用于人口统计学分析。在此，我们建议：（1）利用创新的微流控和统计方法来精确表征不同饮食输入下的个体人口学轨迹，（2）检查发育状态和胰岛素信号传导以及应激反应途径在面对饮食波动时介导生殖模式变化中的作用，以及（3）表征感知在饮食调节生殖模式中的作用。我们将使用定制设计的微流体系统，该系统（1）提供数万个个体的生殖动力学的自动表征，（2）允许精确控制饮食和食物水平，以及（3）能够根据生理状态（例如基因表达水平）对个体进行分类。一个新的框架的基础上随机人口统计学将被用来分析数据，以估计个人的随机内核自然隔离和长寿相关的突变体饲养条件下的饮食限制和暴露于自然发生的线虫相关细菌。感知缺陷突变体将用于区分由感觉输入与代谢状态驱动的生殖调节。总之，这项工作将提供新的和全面的方法来研究这个重要的模型系统中的随机人口统计学，并将提供深入了解如何影响的治疗，导致寿命延长传播整个生殖寿命的个人。