Kowald A, Kirkwood T B
Laboratory of Mathematical Biology, National Institute for Medical Research, London, U.K.
J Theor Biol. 1994 May 7;168(1):75-94. doi: 10.1006/jtbi.1994.1089.
Many different theories of ageing have been proposed, based often on highly specific molecular causes. Recent advances in evolutionary theory support the idea that ageing is caused by progressive accumulation of defects, but indicate that multiple processes are likely to operate in parallel. This calls for an understanding of ageing and longevity in terms of a network of maintenance processes that controls the capability of the system to preserve homeostasis. Here we develop a theoretical model which begins the task of implementing a Network Theory of Ageing. To do this the model integrates the ideas of the Free Radical Theory, describing the reactions of free radicals, antioxidants and proteolytic enzymes, with the Protein Error Theory, describing the error propagation loops within the cellular translation machinery. The simulations show that an increased radical production and/or insufficient radical protection can destabilize an otherwise stable translation system. The model supports the idea that caloric restriction prolongs life via a reduction of the generation of radicals. Another result of the model is that protein half-life increases with time as a natural consequence of the interaction between proteolytic enzymes and radicals. Finally the model strengthens certain evolutionary ageing theories by showing that there is a positive correlation between maintenance related energy consumption and lifespan.
人们已经提出了许多不同的衰老理论，这些理论往往基于高度特定的分子原因。进化理论的最新进展支持衰老由缺陷的逐步积累引起这一观点，但表明多个过程可能同时起作用。这就需要从一个控制系统维持体内平衡能力的维护过程网络的角度来理解衰老和长寿。在此，我们开发了一个理论模型，开始实施衰老网络理论的任务。为此，该模型将描述自由基、抗氧化剂和蛋白水解酶反应的自由基理论与描述细胞翻译机制内错误传播环的蛋白质错误理论相结合。模拟结果表明，自由基产生增加和/或自由基保护不足会使原本稳定的翻译系统不稳定。该模型支持热量限制通过减少自由基的产生来延长寿命这一观点。该模型的另一个结果是，由于蛋白水解酶和自由基之间的相互作用，蛋白质半衰期会随着时间的推移而自然增加。最后，该模型通过表明与维护相关的能量消耗和寿命之间存在正相关，强化了某些进化衰老理论。
