Reiner J M
Mech Ageing Dev. 1978 Jul;8(1):1-13. doi: 10.1016/0047-6374(78)90002-7.
A theoretical model of transcriptional control, in a preliminary form, is presented. The model has a critical boundary between a region of values in which the system is stable and essentially self-perpetuating and a region in which the essential macromolecules tend to disappear and not to be regenerated. The possibility of the transition results from cell division. Variation in the values of kinetic parameters or fluctuation in the partition of the macromolecules between the daughter cells of a division subject some cells in the population to the instability. Cells on the wrong side of the critical boundary may accumulate in G2, and will eventually die, at rates and frequencies depending on the specific peculiarities of various cell types (e.g., tissues). Such phenomena, in association with the characteristic division patterns predicted by the theory, have been observed in vitro and in vivo. "Programmed death" in morphogenesis may be an instance. Problems in the future development of the theory are outlined. The significance of clonal selection for atherogenesis and perhaps oncogenesis is noted. The theory is briefly contrasted with "damage" and "error" theories; and the eventual possibility of constructive intervention in ageing at the molecular level is suggested.
本文提出了一个初步形式的转录控制理论模型。该模型在系统稳定且基本自我维持的数值区域与基本大分子趋于消失且无法再生的区域之间存在一个临界边界。这种转变的可能性源于细胞分裂。动力学参数值的变化或大分子在一个分裂的子细胞之间分配的波动，会使群体中的一些细胞处于不稳定状态。处于临界边界错误一侧的细胞可能会在G2期积累，并最终死亡，其速率和频率取决于各种细胞类型（如组织）的具体特性。这种现象，连同该理论预测的特征性分裂模式，已在体外和体内观察到。形态发生中的“程序性死亡”可能就是一个例子。文中概述了该理论未来发展中存在的问题。指出了克隆选择对动脉粥样硬化和可能的肿瘤发生的意义。该理论与“损伤”和“错误”理论进行了简要对比；并提出了在分子水平对衰老进行建设性干预的最终可能性。
