Dietary Calorie Restriction from Adulthood Through Old Age in Rats: Improved DNA Polymerase beta and DNA Gap Repair Activity in Cortical Neurons

摘要

It is well established now that dietary calorie restriction (CR) leads to extension of life span in many species, although the exact mechanism of this effect is still eluding. In the present study, we examined the effect of 40 CR imposed during a prolonged period of life span (from 6 to 30 months) of rats on the activity of DNA polymerase beta (pol beta) in view of its role in short gap base excision DNA repair and template driven primer extension. DNA pol beta activity is very low at this late age. However, cortical neuronal extracts prepared from CR rats of 30 months age showed significantly higher pol beta protein levels and activity when compared to control 30 month old rats. Yet, one-nucleotide gap repair in old control neurons and an improved efficiency in CR neurons could be visualized only after supplementation of the extracts with T-4 DNA ligase indicating the lack of CR affect on ligase activity. No impressive primer extension activity is seen either in the CR or old control neurons. These results are taken to convey that extended CR through adult life leads to improved pol beta activity and therefore, pol beta dependent DNA gap repair activity.