Dysdifferentiative Nature of Aging: Age-Dependent Expression of MuLV and Globin Genes in Thymus, Liver and Brain in the AKR Mouse Strain

Abstract

The amount and sequence complexity of RNA transcribed by the murine leukemia virus (MuLV) genome and to the alpha- and beta-globin genes in thymus, brain and liver were measured throughout the life span of AKR mice using a cDNA X RNA hybridization technique. RNA complementary to the complete sequence of specific cDNA probes for both MuLV and globin was found in nuclei and cytoplasm of thymus, brain and liver at all ages studied. No significant age-dependent change in the amount or sequence complexity of globin RNA was detected. The amount of MuLV RNA in both nuclei and cytoplasm of thymus increased about five times from 2 to 5 months of age, but no significant change was observed over this age range in MuLV RNA from liver and brain. By the age of 10 months, most of the mice had developed leukemia and the thymus showed a further increase in the amount of MuLV RNA. Nuclear RNA from liver and brain then showed a significant increase in the amount of MuLV, but no change in the amount of MuLV was found in the cytoplasm. No qualitative age-dependent changes in the MuLV RNA sequence complexity in thymus, liver and brain were detected. These results suggest that in the AKR mouse strain for the three tissues studied, an age-dependent relaxation occurs in the repression of the MuLV genome but not for alpha- and beta-globin genes. The rate of the depression of MuLV genes in the short-lived AKR mouse strain appears similar to that of the long-lived C57BL/6J mouse strain. This age-dependent relaxation of MuLV genes appears to be limited to the nuclei. Thus, the presence of a specific regulatory system for the transport of MuLV RNA through the nuclear membrane which does not deteriorate with age is indicated.