Cell Level- Modeling of Aging and Rejuvenation

Abstract

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.