SELECTIVE LOSS OF RIBOSOMAL RNA GENES DURING THE AGING OF POST-MITOTIC TISSUES

Maintenance of long-term genetic integrity in living cells is facilitated by a combination of enzymatic repair mechanisms and cellular selection processes. In dividing cell populations, and in tissues comprised of dividing cells, defective cells can be continuously replaced through the selective propagation of the most viable cells. However, many important organs in higher animals are comprised of non dividing (post-mitotic) cells in which such selection processes can not operate. It was of interest, therefore, to investigate the possibility of genetic damage as a factor in the age-dependent deterioration observed in key post-mitotic tissues such as the nervous and muscular system. The technique of RNA.DNA molecular hybridization was used to measure the dosage of ribosomal RNA genes in selected mitotic and post-mitotic tissues of aging beagle dogs. This approach was chosen both because of the importance of these genes to protein synthesis and in order to test a previously proposed model for the selective loss of such tandemly duplicated genes during aging. The results indicate a substantial decline in the number of ribosomal RNA cistrons in DNA from brain, heart and skeletal muscle of 10-year-old dogs. These findings and the proposed model are discussed in relation to other studies of age-dependent changes in DNA and the possible effects of the observed gene loss on cellular function.