MATHEMATICAL MODELS OF INTERMEDIARY METABOLISM IN AGING

衰老过程中中间代谢的数学模型

• 批准号: 3068455
• 负责人: JOANNE Keene KELLEHER
• 金额: $ 6.41万
• 依托单位: GEORGE WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-05-01 至 1993-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3068455
• 关键词: aging; aminoacid metabolism; glucagon; gluconeogenesis; glutamine; homeostasis; hormone regulation /control mechanism; human old age (65+); laboratory rat; liver cells; liver metabolism; mathematical model; mature animal; metabolism; pharmacology

The goal of this SERCA proposal is to provide the opportunity for career development in the area of mathematical modeling of intermediary metabolism in aging for Dr. Joanne K. Kelleher. The candidate has over ten years experience in laboratory research in intermediary metabolism and an interest in mathematical modeling and aging. The candidate was a NIA post- doctoral fellow and has co-authored a paper describing the application of mathematical models to the field of aging research. Two areas of modeling research have been selected for detailed study in the initial years of the proposal. 1) 'Minimal modeling' is a method for selecting the most concise model capable of describing the physiological system. This process may be essential if models are to be of practical use in understanding complex homoestated systems. 2) 'Control analysis' is a method for analyzing metabolic pathways replacing the notion of "rate limiting steps". Control analysis produces quantitative estimates of the extent to which flux through the entire pathway is controlled by each reaction. While it is recognized that modeling methods are not without short comings, the thesis of this proposal is that application of modeling techniques to the altered metabolic homeostasis of aging will be extremely useful. Experimental investigation will focus on the stimulation of gluconeogenesis by glucagon in isolated rat hepatocytes from adult (6 mo) and aged (24 mo) rats. The sensitivity of hepatocytes to glucagon will be investigated. The long term goal of this candidate is to bring expertise in modeling methodologies to the study of human aging.

SERCA 提案的目标是提供机会 数学建模领域的职业发展 Joanne K. Kelleher 博士的衰老过程中的中间代谢。 候选人具有十年以上实验室经验 对中间代谢的研究和兴趣 数学建模和老化。 该候选人是 NIA 后 博士研究员，并与人合着了一篇论文，描述了 数学模型在衰老研究领域的应用 选择了两个建模研究领域进行详细研究 在提案的最初几年进行研究。 1）“最小建模”是 一种选择最简洁模型的方法 描述生理系统。 这个过程可能是 如果模型要在理解方面具有实际用途，则至关重要 复杂的同态系统。 2）“控制分析”是一种方法 用于分析代谢途径，取代“速率”的概念 限制步骤”。控制分析产生定量估计 通过整个路径的通量的程度 由各反应控制。 虽然人们认识到建模 方法并非没有缺点，本提案的论文 是应用建模技术来改变 衰老的代谢稳态将非常有用。 实验研究将集中于刺激 胰高血糖素在离体大鼠肝细胞中的糖异生作用 成年（6 个月）和老年（24 个月）大鼠。 肝细胞的敏感性 将调查胰高血糖素。 本次活动的长远目标 候选人将把建模方法方面的专业知识带到 人类衰老研究。