INCREASED FREQUENCY OF DELETIONS IN THE MITOCHONDRIAL GENOME WITH AGEOF CAENORHABDITIS-ELEGANS

We have developed a long-extension-PCR strategy which amplifies approx imately half of the mitochondrial genome (6.3 kb) of Caenorhabditis el egans using an individual worm as target. We analyzed three strains ov er their life span to assess the number of detectable deletions in the mitochondrial genome. Two of these strains are wild-type for life spa n; while the third is mutant in the age-1 gene, approximately doubling its maximum life span. At the mean life span in wild-type strains, th ere was a significant difference between the frequency of deletions de tected in the mitochondrial genome compared with the mean number of de letions in young animals. In addition, deletions in the mitochondrial genome occur at a significantly lower rate in age-1 mutants as compare d with wild type. We cloned and identified the breakpoints of two dele tions and found that one of the deletions had a direct repeat of 8 bp at the breakpoint. This is the largest single study (over 900 individu al animals) characterizing the frequency of deletions in the mitochond rial genome as a function of age yet carried out.