MATHEMATICAL MODELS OF INTERMEDIARY METABOLISM IN AGING

该SERCA提案的目标是提供机会， 数学建模领域的职业发展 衰老中的中间代谢。凯莱赫 候选人有十年以上的实验室工作经验 研究中间代谢和兴趣， 数学建模和老化。 候选人是NIA后- 博士研究员，并共同撰写了一篇论文，描述了 数学模型在老龄化研究领域的应用。 选择了两个建模研究领域， 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。 该过程可以 如果模型要在理解中有实际用途， 复杂的家庭系统。 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 在多大程度上通过整个途径的流量是 由每个反应控制。 虽然认识到建模 方法不是没有短句，本论文的建议 是将建模技术应用于 代谢稳态的老化将是非常有用的。 实验研究将集中在刺激 胰高血糖素在离体大鼠肝细胞中的促凋亡作用 成年（6个月）和老年（24个月）大鼠。 肝细胞的敏感性 将研究胰高血糖素。 长期目标是 候选人是把建模方法的专业知识， 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.