MATHEMATICAL MODELS OF INTERMEDIARY METABOLISM IN AGING

这项SERCA提案的目标是为 数学建模领域的职业发展 乔安妮·K·凯莱赫博士衰老过程中的中间代谢。 应聘者有十多年的实验室工作经验 对中间代谢的研究和对 数学建模和老化。这位候选人是NIA的一名职位- 博士，并与人合著了一篇论文，描述了 数学模型在衰老研究领域的应用。 选择了两个领域的建模研究进行详细的 在建议的最初几年学习。1)‘最小建模’是 一种选择最简明模型的方法 描述生理系统。这一过程可能是 如果模型要在理解中具有实际用处，则必不可少 复杂同态系统。2)“控制分析”是一种方法 用来分析新陈代谢途径，以取代“速率”的概念 控制分析产生定量估计 整个通路的流量在多大程度上 由每一种反应控制。虽然人们认识到，建模 方法并不是没有缺点，这一建议的主题是 是将建模技术应用于改变 衰老的代谢动态平衡将是非常有用的。 实验研究将重点放在刺激 胰高血糖素对大鼠肝细胞糖异生作用的研究 成年(6mo)和老龄(24mo)大鼠。肝细胞的敏感性 对高血糖素的反应将被调查。这样做的长期目标是 候选人是将建模方法方面的专业知识带到 研究人类衰老。

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.