Ageing and the mismatch repair system

Age-related accumulation of mutations has been extensively documented, and it has been proposed as one of the prominent causes of malignancies in old age. The present review is focused on the particular case of DNA mismatch r epair system (MMR), that has drawn increased attention for its possible rel evance to malignancy. We also report on our own observations on an age-asso ciated genomic instability that develops with age in the MMR system. Our st udy was performed on DNA samples that were prepared from peripheral blood c ells, obtained at a 10-year interval from young and old human subjects. The two DNA samples from each individual were examined comparatively. The olde r individuals showed a significantly higher rate of microsatellite instabil ity (MSI) in several loci examined, whereas no difference was found between the paired samples of any of the young subjects. We suggest that this incr ease in MSI with age may indicate an overall genomic instability in the eld erly. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.