Normal and Pathological Ageing in the Post-Mitotic Cells of the Brain

Abstract

Most of our discussion of somatic mutation in relation to ageing has been concerned with clonally proliferating cells, with special attention to the cells of the immune system. A significant proportion of natural deaths can, however, be ascribed to degenerative age-associated changes in the central nervous system, where the neurones are all post-mitotic cells incapable of further replication. From our present point of view this situation is of special interest since Orgel’s error-catastrophe concept was originally developed with post-mitotic cells primarily in mind with the initiation of error most probably arising at the level of transcription by RNA polymerase. It is known, however, that there is a consistent small DNA turnover in nerve cells, and one cannot exclude the likelihood that errors in the transcription process may require incidental repair of DNA with its own possibilities of error in the reconstitution of pattern.