Loss of hybridizable ribosomal DNA from human post-mitotic tissues during aging: II. Age-dependent loss in human cerebral cortex — Hippocampal and somatosensory cortex comparison

Abstract DNA was isolated from the hippocampal and from the somatosensory cortex of 13 humans (at autopsy). In both the cortex and hippocampus, the loss of ribosomal DNA (rDNA), as measured through hybridization in the liquid phase, approximates about 0.9% per year. The r value for somatosensory cortex was about −0.7 and that for the hippocampus was about −0.91. The correlation coefficient between the sets of two samples derived from the same individual (two different areas) in +0.945. These results are consistent with those reported concurrently for human myocardium and with earlier studies conducted with beagle dogs, in which only post-mitotic tissues (brain, heart and skeletal muscle) showed measurable decrements in these key genes. To the degree that the synthesis of new proteins is essential for sustained mental activity, these results are consistent with the observations that Nissl substance is more slowly replenished, following exhaustive work by motor cortical cells, and the fact that many older persons experience mental fatigue during continuous mental work at earlier times than do younger persons. The mechanism of loss is not certain, but may well be related to inadequacies in DNA repair systems, thereby allowing deletion of tandemly duplicated genes through cross-over “episome” formation, followed by degradation of the excised DNA segments. The ratio of loss of rDNA hybridizability in human and dogs is about 1 to 7, which approximates the relative ratios of their lifespans (reciprocals).