细胞水平--衰老与年轻化建模

Andrey Koptyug, Yurij Sukhovei, Elena Kostolomova, I. Unger, Vladimir Kozlov
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摘要

要了解与人类衰老和年轻化有关的过程,有赖于实验数据和在不同层面运行的先进模型。现有几种概念和具体的建模方法。然而,现有的任务之一是编制通用模型,将细胞和细胞元素层面的特性与组织、器官和全身等系统层面的特性联系起来。相关模型中的一个关键问题是细胞和亚细胞水平上的交互组件数量巨大,需要正确地表示高层次系统的属性。本文介绍了一种在细胞群体水平上进行建模和模拟以研究衰老和返老还童的可行方法。本文还介绍了根据建模和实验结果得出的初步结论。该模型基于增殖生态位和细胞群中通过增殖和凋亡的相关作用实现细胞数量稳定的概念。重要的是,我们解决了包含大量不同年龄细胞的细胞群的 "衰老 "和 "年轻化 "的定义问题。我们有可能证明,通过维持单一调节物质的浓度,就能实现平衡调节。建议模型的预测和模拟结果与现有出版物中的数据以及为验证模型而专门进行的实验进行了比较。目前,没有任何可用数据与所建议的详细程度的建模结果相矛盾。然而,元素数量不足和采用的统计方法进一步限制了此类建模的进展。要将所建议的方法扩展到包括代表人体组织、器官和身体的现实特征数量,并对衰老和年轻化过程进行适当建模,需要更先进的建模技术。
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Cell Level- Modeling of Aging and Rejuvenation
Understanding processes related to human aging and rejuvenation relies on experimental data and advanced models operating at different levels. There are several existing conceptual and specific modeling approaches. However, one of the existing tasks is compiling generic models linking properties at cell and cell-element levels to properties at systemic levels - tissue, organ, and whole body. One of the critical issues in the relevant models is the enormity of interacting components at the cell and sub-cell levels needed to represent the properties of high-level systems properly. This paper describes a promising approach to modeling and simulation at the cell population level for studying aging and rejuvenation. It also presents initial conclusions formulated based on the results of modeling and experiments coupled to it. The model is based on the concepts of the proliferation niche and homeostatic cell number stabilization in the cell population through the associated action of proliferation and apoptosis. Importantly, we address the issue of defining “aging” and “rejuvenation” for cell populations containing large numbers of cells of different ages. It is possible to demonstrate that homeostatic regulation can be performed by maintaining the concentration of a single regulatory substance. Predictions and simulations of the proposed model are compared to data from existing publications and experiments specifically conducted to validate the model. Currently, none of the available data contradicts the modeling results at the proposed level of detail. However, an inadequate number of elements and the employed statistical approach further limit progress in such modeling. Expanding the proposed method to include a realistic number of features representing human tissues, organs, and body and to allow for proper modeling of aging and rejuvenation processes requires more advanced modeling techniques.
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