COMPUTER ANALYSIS OF AGING IN DICTYOSTELIUM

本申请中提出的研究将继续我们的努力， 定义代谢转换过程中的限速事件， 分化，衰老和死亡的模式系统，网骨藻 盘状突 正在测试的假设是， 负责分化和衰老的生化机制必须是 寻求使用系统分析，在复杂性和集成的水平 远大于迄今为止所考虑的任何理论所包含的。 的 对这一假设的最终检验是证明的预测值， 构建的动力学模型。 我们正在获取建造、测试和 在代谢的各个领域不断扩展模型， 发育和衰老。 具体而言，我们将获得必要的数据（1） 以模拟正常情况下两种细胞类型中的碳水化合物代谢， 微分和在稳态下葡萄糖扰动期间 条件，（2）构建稳态（TFLUX）和过渡 戊糖代谢的METASIM模型，（3）构建过渡模型 （4）建立柠檬酸循环的过渡模型 三种代谢可区分细胞中的碳水化合物代谢 类型

The research proposed in this application will continue our efforts to define rate-limiting events during the metabolic transitions essential to differentiation, aging and death in the model system, Dictyostelium discoideum. The hypothesis being tested is that an understanding of the biochemical mechanisms responsible for differentiation and aging must be sought using a SYSTEMS analysis, at a level of complexity and integration much greater than that encompassed by any theory thus far considered. The ultimate test of this hypothesis is the demonstrated predictive value of kinetic models which are constructed. We are acquiring the data necessary for the construction, testing and continued expansion of models in various areas of metabolism essential to development and aging. Specifically, we will obtain the data necessary (1) to simulate carbohydrate metabolism in the two cell types during normal differentiation and during glucose perturbation under steady-state conditions, (2) to construct a steady-state (TFLUX) and transition (METASIM) model of pentose metabolism, (3) to construct a transition model of the citric acid cycle, and (4) to construct transition models of carbohydrate metabolism in the three metabolically distinguishable cell types.