Information and clonal concepts in ageing.

Abstract

A model based on information theory and one based on somatic mutation in an expanding pool of cells are combined to give a theory of ageing. A mathematical formula, based on concepts from information theory, gives a close fit to the age incidence of mortality and disease in middle and old age. The basic concept is that biological systems process information and make decisions to maintain their integrity. But the decision process is fallible and significant errors could lead to disease or death. Decay in the components of the system will lead to a rising error rate with age and the form of the curve will be influenced by redundancy which is a fundamental property of information systems. In addition it is suggested that an important part of the decay in the decision process is due to a subset of mutant stem cells which have a proliferative advantage and slowly expand in number throughout life. This idea is derived from application of a model of somatic mutation in expanding cells to data in cancer and on the increase of dominant mutations with paternal age. This composite view explains why ageing is less subject to the vagaries of the extrauterine environment than suggested by the simple information model and points to a significant role for the intrauterine environment in the ageing process.