Differential display analysis of gene expression indicates that age-related changes are restricted to a small cohort...

It is clear that there is a genetic component associated with the ageing process. Although evolutionary theory has suggested that the activity of certain genes may facilitate ageing by favouring resource utilisation by the germ cells at the expense of somatic cells, there is reason to believe that the senescent phenotype, which is the endpoint of the ageing process, may be due to alterations in the levels of expression of other genes. To investigate this situation we have used the differential display technique to survey gene expression during ageing of the rat brain, heart and liver. By optimising this technique it is possible to identify up to 10000-14000 PCR products, which represent genes expressed in the tissue under study. Interestingly, only a relatively small cohort (approximately 2%) of these genes appear to show significant changes in their levels of expression during ageing. Characterisation of the latter has so far revealed certain genes, such as glial fibrillary acidic protein, which are associated with the senescent phenotype. It has also revealed that the level of fos, a component of the AP-1 transcription factor, decreases with age, which has implications for AP-1 regulated genes. The differential display technique has also revealed an increase in mitochondrial RNA during ageing of the heart, which may be due to a gene dosage effect caused by the presence of increased numbers of mitochondrial genomes in myocytes in old age. The differential display technique therefore appears to offer a powerful tool for identifying genes which contribute to the emergence of a senescent phenotype.