elderly populations.

Genotype profiles of loci encoding DNA repair enzymes were compared between a cohort of newborns (n=290) and retired individuals (average age at sampling 70.02 years; n=430) to identify potential associations with longevity. Seven polymorphisms at four loci involved in DNA repair were analyzed, but no differences in genotype frequencies at the four SNP loci were observed, indicating no evidence of association with longevity in this population. However, significant differences in frequency of certain repeat sizes at three microsatellite loci were detected, but since there is no known functional consequence of these repeat lengths, the action of selection cannot yet be ascribed.

Over 400 polymorphisms have been identified in 80 genes that have been screened for variation, and non-synonymous polymorphisms can have functional consequences that could alter the ability to repair DNA damage. Our genetic material is under continual assault from extrinsic genotoxic agents and intrinsic metabolic processes, and as people age, they will have to contend with a lifetime of increasing exposure to DNA-damaging agents. To cope with this barrage of DNA damage, there are a number of DNA repair pathways that are responsible for its detection and repair. Over 115 genes so far have a recognized role in DNA damage recognition and repair, and exposure to DNA-damaging agents is reflected in age-related increases in somatic mutations in both nuclear and mitochondrial DNA and in chromosomal translocations.

The study populations consisted of umbilical cord blood samples from an unselected newborn population (n=290) and retired male radiation workers previously employed at the Sellafield nuclear facility (n=430). Genotyping analysis was conducted on seven polymorphisms in four DNA repair genes: 2 SNPs and 1 microsatellite in XRCC1 of the BER pathway, 1 SNP and 1 microsatellite within XRCC3 of the HR pathway, 1 SNP in XRCC4 and 1 microsatellite in XRCC5, both components of the NHEJ pathway. All four SNP polymorphisms were found to be in Hardy-Weinberg equilibrium. Comparison of newborn and retired worker genotype frequencies at the 4 SNP loci was undertaken using v2 analysis, and there was no evidence for differing gene frequencies between the newborn cohort and the retired worker population.