In vitro 'ageing' and nuclear template function

The fundamental cause(s) of senescent deterioration remain(s) to be established. Numerous attempts have been made to relate changes found at the cellular level with altered or failing functional changes occurring at the molecular level. However, the apparently contradictory published data often make it very difficult if not impossible, to decide whether any conclusive evidence has been provided. In this article, we have reviewed the attempts to relate in vitro 'ageing' with alterations in nuclear template function and have made brief mention of the few complementary in vivo experiments. Results from studies of chromatin function during in vitro 'ageing' in general favour the suggestion that the reduction in template activity with increasing 'age' may result from the loss of cellular division potential, so being an effect rather than a cause of in vitro 'ageing'. However, nuclear control of 'ageing' via specific transcriptional mechanisms cannot be excluded by these data. It is possible that minor or discrete species of RNA are involved, but their investigation and detection await the development of new or more sensitive methodologies. Therefore, published data are consistent with theories of genetically programmed cellular senescence and terminal differentiation, but they do not allow us to decide firmly in favour of one or the other.