Towards a network theory of ageing: a model combining the free radical theory and the protein error theory.

Abstract:  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.