Arino O, Kimmel M, Webb G F
Department of Mathematics, University of Pau, France.
J Theor Biol. 1995 Nov 7;177(1):45-57. doi: 10.1006/jtbi.1995.0223.
hortening of telomeres is one of the supposed mechanisms of cellular aging and death. An important question related to this so-called "end-replication" hypothesis is whether it can explain in quantitative detail the dynamic of cell sensescence in vitro and in vivo. A natural way to answer this question is to use mathematical modeling. In this paper, the models were successfully fitted to data on cultured fibroblasts from two different sources assuming that after reaching the Hayflick checkpoint on a single chromosome cells cease to proliferate. The main conclusion is that the end-replication hypothesis provides an explanation for the cell aging process which is quantitatively consistent with the data. As a secondary outcome, estimates were obtained of the rate of shortening of telomeres and several interesting mathematical results for branching processes with infinite type spaces arise.
端粒缩短是细胞衰老和死亡的一种推测机制。与这个所谓的“末端复制”假说相关的一个重要问题是,它能否在数量上详细解释体外和体内细胞衰老的动态过程。回答这个问题的一个自然方法是使用数学建模。在本文中,假设单条染色体上的细胞达到海弗利克极限后停止增殖,这些模型成功拟合了来自两个不同来源的培养成纤维细胞的数据。主要结论是,末端复制假说为细胞衰老过程提供了一种在数量上与数据一致的解释。作为次要结果,获得了端粒缩短速率的估计值,并且出现了关于具有无限类型空间的分支过程的几个有趣的数学结果。