Abstract The interaction between nuclear (nDNA) and mitochondrial DNA (mtDNA) methylation is not well known in the healthy population. The D-loop methylation level of the Olympic champions ( N = 58) was significantly lower than that of non-champions ( N = 32) (~ 36% unadjusted mean difference p = 0.016, sex and age adjusted p = 0.017). Interestingly, the robust linear analysis revealed that biological sex is a significant factor in mtDNA D-loop methylation (estimate = 1.521, p = 0.033). On the other hand, we cannot find relationships between the methylation levels of mtDNA and nuclear DNA, suggesting distinct regulation of the methylation/demethylation process of mtDNA and nuclear DNA. DNA methylation-based aging clocks showed a significant relationship with the levels of Klotho, irisin, and its receptor (irisin receptor integrin alpha-V), as well as with epigenetic regulators such as ten-eleven translocation enzyme 2, which were measured using enzyme-linked immunosorbent assay. Therefore, the data suggest a complex regulatory process of epigenetic aging and raise the possibility that D-loop methylation may have functional relevance in health, which remains to be explored. Graphical abstract
Téglás et al. (2026) studied this question.