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<p>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 (<i>N</i> = 58) was significantly lower than that of non-champions (<i>N</i> = 32) (~ 36% unadjusted mean difference <i>p</i> = 0.016, sex and age adjusted <i>p</i> = 0.017). Interestingly, the robust linear analysis revealed that biological sex is a significant factor in mtDNA D-loop methylation (estimate = 1.521, <i>p</i> = 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.</p> Graphical abstract <p></p>

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Epigenetic insights of Olympic champions: nuclear and mitochondrial DNA methylation and regulators of aging

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月17日

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  • Timea Teglas,
  • Ferenc Torma,
  • Zoltan Bori,
  • Dora Aczel,
  • Gergely Babszky,
  • Takuji Kawamura,
  • Mitsuru Higuchi,
  • Gu Yaodong,
  • Muhammad Lee,
  • Steve Horvath,
  • Zsolt Radak

摘要

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