DIFFERENTIAL DISPLAY ANALYSIS OF GENE-EXPRESSION INDICATES THAT AGE-RELATED-CHANGES ARE RESTRICTED TO A SMALL COHORT OF GENES

It is clear that there is a genetic component associated with the agei ng process. Although evolutionary theory has suggested that the activi ty of certain genes may facilitate ageing by favouring resource utilis ation by the germ cells at the expense of somatic cells, then is reaso n to believe that the senescent phenotype, which is the endpoint of th e ageing process, may be due to alterations in the levels of expressio n of other genes. To investigate this situation we have used the diffe rential display technique to survey gene expression during ageing of t he rat brain, heart and liver. By optimising this technique it is poss ible to identify up to 10000-14000 PCR products, which represent genes expressed in the tissue under study. Interestingly, only a relatively small cohort (approximate to 2%) of these genes appear to show signif icant changes in their levels of expression during ageing. Characteris ation of the latter has so far revealed certain genes, such as glial f ibrillary acidic protein, which are associated with the senescent phen otype. 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 inc reased numbers of mitochondrial genomes in myocytes in old age. The di fferential display technique therefore appears to offer a powerful too l for identifying genes which contribute to the emergence of a senesce nt phenotype. (C) 1998 Elsevier Science Ireland Ltd. All rights reserv ed.