Decreased fidelity of DNA polymerases and decreased DNA excision repair in aging mice: effects of caloric restriction.
Hepatic DNA polymerases from calorie restricted and ad libitum 26 month old C57BL/6 mice showed a decline in fidelity of nucleotide incorporation compared with weanling animals. Both alpha and beta polymerases from calorie restricted aged mice exhibited a higher level of fidelity than polymerases from ad libitum aged mice. UV-initiated unscheduled DNA synthesis was significantly higher in hepatocytes from weanling and 18 month old calorie restricted animals compared with cells from 18 month old ad libitum animals, while MMS-initiated unscheduled DNA synthesis did not differ significantly between cells from young and old or ad libitum and calorie restricted animals. These data suggest that calorie restriction could play a significant role in decreasing the age-related decline of cellular mechanisms expected to reduce the rate at which mutations accumulate during aging, and could potentially prolong the onset age of mutation-associated diseases of the elderly.
Srivastava
V K
VK
Department of Anatomy and Public Health, College of Veterinary Medicine, Texas A&M University, College Station 77843.
Busbee
D L
DL
D000375:Aging / Q000502:physiology*; D000818:Animals; D002478:Cells, Cultured; D004256:DNA Polymerase I / Q000378:metabolism*; D004257:DNA Polymerase II / Q000378:metabolism*; D004260:DNA Repair; D004261:DNA Replication; D002149:Energy Intake; D043211:Exodeoxyribonuclease V; D005090:Exodeoxyribonucleases / Q000378:metabolism; D005260:Female; D008099:Liver / Q000201:enzymology / Q000254:growth & development*; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation
D004256:DNA Polymerase I; D004257:DNA Polymerase II; D005090:Exodeoxyribonucleases; D043211:Exodeoxyribonuclease V