Decline of nucleotide excision repair capacity in aging Caenorhabditis elegans

Background Although Caenorhabditis elegans is an important model for the study of DNA damage-and repair-related processes such as aging, neurodegeneration and carcinogenesis, DNA repair is poorly characterized in this organism. We adapted a quantitative PCR assay to characterize repair of UVC radiation-induced DNA damage in Celegans, and then tested whether DNA repair rates were affected by age in adults. Results UVC radiation induced lesions in young adult Celegans with a slope of 0.4-0.5 lesions per 10kb DNA per 100 Joules/m(2), in both nuclear and mitochondrial targets. L1 and dauer larvae were > 5-fold more sensitive to lesion formation than young adults. Nuclear repair kinetics in a well-expressed nuclear gene were biphasic in non-gravid adult nematodes: a faster, first order ( t(1/2) similar to 16 h) phase lasting similar to 24 h and resulting in removal of similar to 60% of the photoproducts was followed by a much slower phase. Repair in 10 nuclear DNA regions was 15% and 50% higher in more actively transcribed regions in young and aging adults, respectively. Finally, repair was reduced 30-50% in each of the 10 nuclear regions in aging adults. However, this decrease in repair could not be explained by a reduction in expression of nucleotide excision repair genes, and we present a plausible mechanism, based on gene expression data, to explain this decrease. Conclusions Repair of UVC-induced DNA damage in Celegans is similar kinetically and genetically to repair in humans. Furthermore, this important repair process slows significantly in aging Celegans, the first whole organism in which this question has been addressed.