Age-dependent structural changes in human neuronal chromatin.

After partial digestion with micrococcal nuclease, DNA was extracted from nuclei of cerebral cortex neurons from young (23--36 y.) and old (78--85 y.) humans. The DNA fragments were subjected to gel electrophoresis, and their base-pair content determined. The nucleosomal DNA repeat length was found to increase from 170 (+/- 18) base-pairs in the young group to 199 (+/- 8) base-pairs in the old group. This increase of 29 base-pairs appears to be confined to the linker region of the nucleosomal DNA, since the core-DNA was always found to contain approx. 140 base-pairs. In addition, the amount of nuclear DNA digested by the micrococcal nuclease was observed to vary with age: after 30 min. of incubation at 37 degrees C hydrolysis of up to 80% of the nuclear DNA in the young but only up to 60% in the old neuronal nuclei was achieved. The age-dependent increase in chromosomal DNA repeat length is a direct proof of alterations in the basic chromatin structure with aging. It cannot be decided, however, whether the change in DNA digestibility is dependent on alterations of the chromatin basic structure, its superstructure, or both.