Gene expression in different cell types of aging rat brain.

"Bound" and "free" RNA polymerase activities were assessed in the nuclear fraction of cerebral cortical, neuronal, astroglial, and oligodendroglial cells obtained from rats of young, adult, and old ages. Significant decreases in both the bound and free polymerase II activities were noticed in old brain, as compared to adult brain, in neuronal and oligodendroglial nuclei. In astroglia, only the free polymerase II was found to be affected. No effect of aging could be seen on the activity of bound RNA polymerase I + III. The free RNA polymerase I + III activity was increased from adult to old age in neuronal nuclei, but unchanged in oligodendroglial and astroglial nuclei. The age-dependent reduction in RNA polymerase II was maximum in oligodendroglial cells, whereas it was least, although still significant, in neuronal cells. DNA isolated from old brain was unable to enhance the transcriptional activity when added to chromatin preparations obtained from rat brains of any of the above ages and the "old" chromatin was unable to accept even the "young" DNA as additional exogenous template. It is concluded that the reduced gene expression noticed in old brain nuclei is due to both altered chromatin/DNA structure and inadequate levels of free RNA polymerase II.