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The relative proportions of DNA-polymerases alpha, beta, delta and epsilon (pols alpha, beta, delta and epsilon ) activities in isolated neuronal and astroglial cell fractions from developing, adult and aging rat brain cerebral cortex, were examined. This was achieved through a protocol that takes advantage of the reported differential sensitivities of different DNA-polymerases towards certain inhibitors like butylphenyl and butylanilino nucleotide analogs, 2',3'-dideoxythymidine triphosphate (ddTTP), monoclonal antibody of human alpha polymerase and the use of two template primers as substrates. The results indicate that while DNA-polymerase beta (pol beta) is the predominant enzyme, significant levels of DNA-polymerases alpha and delta/epsilon (pols alpha and delta/epsilon ) are also present in both cell types at all the post-natal ages studied. A notable difference regarding the relative abundance of DNA-polymerases other than beta is the higher percentage of pol delta/epsilon in neurons and a more sustained pol alpha activity through the life span in astroglia. The presence of detectable proportion of DNA-polymerases other than beta (particularly the delta/epsilon type) may be taken to indicate their role in long patch base excision repair as well as in other modes of DNA repair.

A close relationship between the DNA repair potential of various organisms and their rate of aging has been long suspected. We have been looking into the steps of the DNA repair process in isolated neurons from rats of different ages. Unscheduled DNA synthesis (UDS) was low in aging neurons, and also the response of these cells to raise their DNA repair capacity against a mutagenic challenge was poor. Attempts to identify the possible defective locus in the overall DNA repair pathways indicated that the step involving DNA polymerase may be defective. The activity of DNA polymerase‐β, the most predominant DNA polymerase in neurons that is generally considered to be a short‐patch repair enzyme, shows a significant decrease in aging neurons. Northern and Southern blotting and immunotitration experiments suggest that there may be an accumulation of inactive β polymerase molecules in the aging rat brain. Most recent preliminary studies reveal significant 3′‐5′ exonuclease activity in rat neurons at all ages. However, extension of a primer in a synthetic oligo duplex, either with a mismatch or correct base pair at the 3′ end of the primer, was low in neurons of any age and was very poor (almost undetectable) in older ones. Supplementation of neuronal extracts with pure polymerase enzyme revealed that only polymerase β, but not polymerase α, was able to increase the primer extension activity significantly in old neurons. These findings are taken to indicate an age‐dependent decline in the DNA repair capacity of neurons and that DNA polymerase β is a key player in the DNA repair mechanisms of nerve cells.

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