Suma Daniel, Acun Aylin, Zorlutuna Pinar, Vural Dervis Can
Department of Chemical and Biomolecular Engineering, University of Notre Dame, Notre Dame, IN, USA.
Bioengineering Graduate Program, University of Notre Dame, Notre Dame, IN, USA.
R Soc Open Sci. 2018 Feb 21;5(2):171395. doi: 10.1098/rsos.171395. eCollection 2018 Feb.
The mortality rate of many complex multicellular organisms increases with age, which suggests that net ageing damage is accumulative, despite remodelling processes. But how exactly do these little mishaps in the cellular level accumulate and spread to become a systemic catastrophe? To address this question we present experiments with synthetic tissues, an analytical model consistent with experiments, and a number of implications that follow the analytical model. Our theoretical framework describes how shape, curvature and density influences the propagation of failure in a tissue subjected to oxidative damage. We propose that ageing is an emergent property governed by interaction between cells, and that intercellular processes play a role that is at least as important as intracellular ones.
许多复杂的多细胞生物的死亡率会随着年龄增长而上升,这表明尽管存在重塑过程,但净衰老损伤仍是累积性的。但这些细胞层面的小问题究竟是如何累积并扩散,进而演变成一场系统性灾难的呢?为了解决这个问题,我们展示了对合成组织进行的实验、一个与实验相符的分析模型,以及基于该分析模型得出的一系列推论。我们的理论框架描述了形状、曲率和密度如何影响遭受氧化损伤的组织中故障的传播。我们提出,衰老是一种由细胞间相互作用所决定的涌现特性,并且细胞间过程所起的作用至少与细胞内过程同样重要。