Age-Related Differences in the Number of Ribosomal RNA Genes of Mouse TissuesGaubatz J.W. · Cutler R.G.
Laboratory of Cellular and Comparative Physiology, Gerontology Research Center, National Institute on Aging, National Institutes of Health, PHS, US Department of Health, Education and Welfare, Bethesda and Baltimore City Hospitals, Baltimore, Md.
An age-related change in DNA sequences coding for rRNA was investigated by: (1) hybridizing DNA with an excess of rRNA to assay for quantitative changes in rRNA gene dosage, and (2) examining physiochemical properties of rRNA·DNA hybrids to determine possible qualitative changes in informational content. The rRNA gene dosage (as estimated by the amount of rRNA able to hybridize to total DNA) was determined in liver, brain, kidney and spleen tissues throughout the life span of female mice from the C57BL/6J inbred mouse strain. The rRNA gene dosage (number of genes per haploid genome) is 100–110 genes in all tissues up to 800 days, with the exception of liver tissue. Liver tissue in mice 10–200 days old contains only about 85 genes. Between the ages of 200–350 days, however, the rRNA gene dosage of liver cells increased to a level equal to that found for other tissues. Past 800 days, a decrease in rRNA gene dosage is observed for all tissues examined. The decrease ranges from 9 to 44%, depending upon the age and tissue investigated. Total mouse embryo also exhibits a low rRNA gene dosage, which is similar to that found for young mouse liver. As a function of age, no substantial changes were detected in the physiochemical properties of the rRNA•DNA hybrid, as measured by thermal stability, sensitivity to RNase treatment, or hybridization kinetics. Decreases in the rRNA hybridization level found for the very old mice may reflect an actual loss of the genes or an inhibition of hybridization due to an age-dependent accumulation of cross-linked chromosomal proteins or other DNA-adducts at the rRNA gene loci. Recovery of hybridization, after an extensive deproteinization treatment of single-stranded DNA, supports this latter interpretation.
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