Faculty of Civil Engineering, University of Zagreb, Fra Andrije Kačića Miošića 26, Zagreb 10000, Croatia.
Ruđer Bošković Institute, Bijenička 54, Zagreb, 10000, Croatia.
J Theor Biol. 2019 Mar 21;465:78-89. doi: 10.1016/j.jtbi.2019.01.007. Epub 2019 Jan 8.
The molecular mechanisms that control the limited number of human cell divisions has occupied researchers ever since its first description in 1961. There is evidence that this limited growth capacity, referred to as cellular or replicative senescence, is the basis for organismal ageing. Numerous studies point to the molecular mechanisms of telomere involvement in this phenomenon. A hallmark of cell senescence is high stochasticity where individual cells enter senescence in a completely random and stochastic fashion. Therefore, mathematical modelling and computational simulations of telomere dynamics are often used to explain this stochastic nature of cell ageing. Models published thus far were based on the molecular mechanisms of telomere biology and how they dictate the dynamics of cell culture proliferation. In the present work we propose an advanced model of telomere controlled cell senescence based on abrupt telomere shortening, thus explaining some important but thus far overlooked aspects of cell senescence. We test our theory by simulating the proliferative potential and two-sister experiment originally conducted by Smith and Whitney in 1980.
自 1961 年首次描述以来，控制人类细胞分裂次数的分子机制一直吸引着研究人员。有证据表明，这种有限的生长能力，称为细胞或复制衰老，是生物体衰老的基础。许多研究指出端粒在这一现象中的分子机制。细胞衰老的一个标志是高度随机性，即个别细胞以完全随机和随机的方式进入衰老。因此，端粒动力学的数学建模和计算模拟通常用于解释细胞衰老的这种随机性。迄今为止发表的模型基于端粒生物学的分子机制以及它们如何决定细胞培养增殖的动力学。在目前的工作中，我们提出了一种基于端粒突然缩短的端粒控制细胞衰老的先进模型，从而解释了细胞衰老的一些重要但迄今为止被忽视的方面。我们通过模拟史密斯和惠特尼 1980 年进行的增殖潜力和两个姐妹实验来检验我们的理论。
