Investigation of the effects of DNA conformational changes on lifespan and cancer resistance in rodents

Contemporary research increasingly moves beyond the genetic code of DNA to focus on structural variations that significantly influence cancer, hereditary diseases, aging, and gene expression. Conformational changes, such as the transition of DNA from the B form to the A or Z forms, play a critical role in determining the molecule's flexibility, stability, and resistance to damage. Molecular factors such as sugar puckering and DNA methylation contribute to these structural transformations. This study represents the first investigation into the potential relationships between DNA conformational changes, lifespan, and cancer resistance in two rodent species. Liver DNA samples from the long-lived and naturally cancer-resistant Nannospalax xanthodon and the comparatively shorter-lived and cancer-susceptible Rattus rattus were analyzed using infrared spectroscopy and principal component analysis (PCA). The results revealed that N. xanthodon exhibited more frequent transitions from the A form to the B and Z forms of DNA, while the B form was predominant in both species. N-type (C3-endo) sugar puckers, associated with the A and Z forms, were notably more prevalent in N. xanthodon, whereas S-type puckers characteristic of B-form DNA were detected at lower levels in this species. Additionally, interspecies variations in nucleobase methylation–associated structural modifications were quantitatively assessed. The findings support the hypothesis that the unique DNA structural characteristics of N. xanthodon may be linked to its longevity and cancer resistance. Moreover, they provide novel insights into how different DNA conformations, along with backbone and base–sugar structural features, may play significant roles in modulating aging and suppressing cancer development.