Aging increases DNase gamma, an apoptosis-related endonuclease, in rat liver nuclei: effect of dietary restriction.

Organ-specific endonuclease might play a role in the age-related increase in apoptosis in laboratory rodent tissues. In nuclear extracts from liver tissues of male F344 rats, the DNase activity gel system identified DNase gamma, Ca(2+)/Mg(2+)-dependent endonuclease. The enzyme activity, which was measured at 3, 6, 16, and 24 months (mo) of age, was significantly increased between 16 and 24mo in control rats fed ad libitum (AL). The expression level of DNase gamma-mRNA, estimated by a semi-quantitative reverse transcription-polymerase chain reaction method, was also increased at 24mo in group AL. The proportion of immunohistochemically DNase gamma-positive cells, most of which were light-microscopically confined to apoptotic cells, was also significantly increased between 16 and 24mo. Dietary restriction, a powerful anti-aging intervention, which was achieved by providing 70% of the mean food intake in group AL from 6 weeks of age, inhibited the age-related increase in the enzyme activity and the proportion of immunostained cells; for the mRNA level, statistical significance was not obtained. The present study suggests that DNase gamma is involved in an age-related increase in the apoptosis of rat liver, and that CR inhibits the increase as it minimized the age-related increase in the fraction of DNA-damaged hepatocytes susceptible to apoptosis.