EFFECTS OF AGING AND DIETARY RESTRICTION ON DNA-POLYMERASES - GENE-EXPRESSION, ENZYME FIDELITY, AND DNA EXCISION REPAIR

Hepatic DNA polymerases isolated from young and old C57BL/6N mice fed ad libitum or calorically restricted differed in chromatographic characteristics, binding affinity for DNA template-primer, specific activity, and fidelity of synthesis. DNA polymerase alpha-total and specific activity declined slightly, while the nucleotide misincorporation frequency increased dramatically, with increased age of the donor animals. A positive correlation was observed between polymerase alpha-specific activity and the affinity of enzyme binding to activated DNA template-primer. Both the age-associated decline in enzyme activity and the decrease in fidelity of synthesis were modified by dietary restriction, with higher specific activity levels and lower misincorporation frequencies for DNA polymerases from dietarily restricted animals compared with ad libitum animals of all ages. Fidelity of both DNA polymerase alpha and beta-increased following treatment with the phosphoinositide hydrolysis product inositol-1,4-bisphoshate. The data suggest that dietary restriction could play an important role in decreasing the age-associated decline in function of physiological systems sensitive to decreased or defective DNA synthesis.