Structural features of DNA and their potential contribution to blind mole rat (Nannospalax xanthodon) longevity

Recent research has shifted the focus from the genetic code of DNA to its structural variations, which significantly impact cancer, genetic diseases, and gene regulation. Structural changes, such as the transition from B-DNA to A-DNA, influence DNA stability and flexibility and are affected by factors like DNA methylation and sugar puckering. This study is the first to investigate the relationship between DNA conformational changes and lifespan in two rodent species. The analysis focused on long-lived Nannospalax xanthodon and shorter-lived Rattus rattus, utilizing infrared spectroscopy and principal component analysis (PCA) to examine liver DNA. Results indicated that transition from B-form to A- and Z-forms were more prevalent in N. xanthodon than in R. rattus. However, the dominant DNA conformations in both species are in B-form. Additionally, N-type sugar puckers (C3-endo conformation), associated with these DNA forms, were more prominent in N. xanthodon. In contrast, S-type sugar puckers (C2-endo conformation), characteristic of B-DNA, were found at lower levels in N. xanthodon. Furthermore, the variations in methylation-specific structural modifications of nucleobases were quantitatively assessed among these species. The study proposes a significant connection between the long lifespan of N. xanthodon, which live underground, and their unique DNA structure, offering insights into how different DNA forms, as well as the conformations of their backbone and sugar-base components, may affect longevity, highlighting potential research avenues regarding the biomolecular aspects of aging.