Analysis of conformation and function of the chromatin of the brain of young and old rats.

Digestion of nuclei of the cerebral hemisphere of young (18-20 week) and old (90-97 week) rats by DNase I shows that the rate and extent of digestion is lower in the old. Time course analysis of the DNA fragments produced by DNase I by polyacrylamide gel electrophoresis shows that more of the lower base pair fragments are produced in the young. Also, the rate of production of these fragments is higher in the young than in the old. Assay of template-engaged RNA polymerase II (alpha-amanitin sensitive) shows that in the old it is only about 50% of that of the young. Addition of exogenous eukaryotic (wheat germ) RNA polymerase II is not able to restore transcription of the chromatin in the old to the level of the young. These data show that chromatin undergoes increasing condensation as a function of age, resulting in decreased transcriptional activity in old age.