DNA Repair

Premature ageing is a universal problem for DS people, including a far higher risk of developing Alzheimer’s disease (Opitz and Gilbert-Barness, 1990). This observation suggests a fault in the integrity of the DNA repair system. Chiricolo et al (1993) investigated whether zinc supplementation affected the maintenance of DNA integrity by damaging lymphocyte DNA with radiation in vitro, before and after four months of zinc supplementation, and observing the rates of repair. The finding was that before supplementation the DNA damage (which was normal) was repaired extraordinarily rapidly when compared with the cells from normal children. The authors suggest that persistent oxidative stress may mean that DNA repair enzymes are activated in higher numbers in DS, a possible explanation for the increased rate of repair. It may even be that zinc deficiency contributes to this oxidative stress. They also suggest that the high speed of repair is likely to mean more mistakes are made and that “it could contribute to neurodegeneration and precocious ageing which are both hall-marks of the system.” (Chiricolo et al). After the period of zinc therapy the damage received by the DS lymphocytes was the same as before, but the rate of DNA repair was significantly reduced, back down to a normal, and presumably more accurate, speed.

Thus the paper shows that zinc does not appear to have a protective effect against DNA damage - at least not radiation damage - but rather modulates the speed of repair and so probably its accuracy. The authors speculate that this is because four months of zinc therapy was enough time to reduce the oxidative stress, but this author believes it is also possible that zinc is a requirement for one or more enzymes which regulate DNA repair. Possibly this could be investigated in vitro, without zinc supplementation in vivo, to observe the effect of immediate availability of zinc ions rather than a slow build up of effects associated with a gradual rise of zinc status to normal. Though this is only one paper it appears to be the first that demonstrates a nutritional intervention apparently affecting DNA repair, and so is a ground-breaking paper.