Genetic errors leading to major DNA repair dysfunction cause a variety of conditions that look a lot like accelerated aging, at least in some aspects of their progression. Here researchers examine small variations in genes associated with DNA repair in a human population, but - as is usually the case in studies of human genetic variation - fail to find a robust correlation with longevity, or one that holds up across different data sets:
DNA-damage response and repair are crucial to maintain genetic stability, and are consequently considered central to aging and longevity. Here, we investigate whether this pathway overall associates to longevity, and whether specific sub-processes are more strongly associated with longevity than others. Data were applied on 592 SNPs from 77 genes involved in nine sub-processes: DNA-damage response, base excision repair (BER), nucleotide excision repair, mismatch repair, non-homologous end-joining, homologous recombinational repair (HRR), RecQ helicase activities (RECQ), telomere functioning and mitochondrial DNA processes.
The study population was 1089 long-lived and 736 middle-aged Danes. A self-contained set-based test of all SNPs displayed association with longevity, supporting that the overall pathway could affect longevity. Investigation of the nine sub-processes [indicated] that BER, HRR and RECQ associated stronger with longevity than the respective remaining genes of the pathway. For HRR and RECQ, only one gene contributed to the significance, whereas for BER several genes contributed. These associations did, however, generally not pass correction for multiple testing. Still, these findings indicate that, of the entire pathway, variation in BER might influence longevity the most. These [results] were not replicated in a German sample. This might, though, be due to differences in genotyping procedures and investigated SNPs, potentially inducing differences in the coverage of gene regions. Specifically, five genes were not covered at all in the German data. Therefore, investigations in additional study populations are needed before final conclusion can be drawn.