In vivo studies on the age-dependent decrease of the rates of total and mRNA synthesis in the brain cortex of rats

Abstract

The membrane hypothesis of aging (Zs.-Nagy, I., 1978, J. Theor. Biol. 75, 189–195) attributes the primary role in cellular aging to an age-dependent decrease of the passive potassium permeability of the cell membrane which is due most probably to free-radical damage of the membrane components. As a consequence, the intracellular and intranuclear ionic strength increases resulting in a condensation of the chromatin and a slowing down of the synthetic processes performed by the nucleus. In this concept it was of importance to reveal whether the rates of total and mRNA synthesis display any age-dependent alteration parallel with the change of membrane permeability of the brain nerve cells. Experiments were performed using tritiated uridine incorporation measurements and suitable preparation techniques in young, adult and old rats (1.5, 13 and 25 mth of age, respectively). Comparisons of the incorporation rates revealed a very considerable decrease in the rate of synthesis of both the total and polyadenylated RNA (polyA + RNA) between the ages of 13 and 26 mth. The old animals displayed only about 55 and 67% of the rate of synthesis for the 2 classes of RNA, respectively, as compared to the young and adult rats, if the results are expressed as dpm/mg RNA. However, the decreases are even more pronounced (34 and 41%) if the results are expressed on a dry weight basis. The results obtained are compatible with the membrane hypothesis of aging.