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<p>Growing evidence shows that epigenetic modification and mitochondrial dysfunction are hallmarks of aging and are associated with the development of a wide range of age-related diseases. Mitochondrial biogenesis, which is marked by mitochondrial DNA copy number (mtDNAcn), is one of the major regulations of mitochondrial function by a set of transacting elements, including mitochondrial DNA polymerase gamma (POLG), working on the mtDNA control region. In this study, we investigated the mtDNAcn and the methylation status at both mtDNA control and POLGA promoter regions in human blood cells from individuals with a wide range of ages. A total of 119 blood samples were collected, including 24 umbilical cord blood samples from newborns and 95 peripheral blood samples from individuals aged 18 to 96&#xa0;years. We observed an increase in mtDNAcn, as well as a rise in the methylation levels of the mtDNA control region during aging, particularly in subjects aged ≥ 45. In addition, a positive correlation was also found between the methylation levels of the 4th CpG site in the <i>POLGA</i> promoter region and mtDNAcn during aging. These results suggest epigenetic regulation at mitochondrial and nuclear genes for mitochondrial biogenesis during aging in human blood cells.</p> Graphical abstract <p></p>

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Elevated mtDNA copy number in older adults is linked to methylation of mitochondrial and nuclear regulatory regions

  • 期刊论文

  • 发表日期：

    2025年12月12日

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  • Hongbo Chi,
  • Hongying Shu,
  • Yingmei Yang,
  • Yuji Ikeno,
  • Jiong Wu,
  • Zhihong Wang,
  • Habil Zare,
  • Mikhail Alexeyev,
  • Yidong Bai

摘要

Growing evidence shows that epigenetic modification and mitochondrial dysfunction are hallmarks of aging and are associated with the development of a wide range of age-related diseases. Mitochondrial biogenesis, which is marked by mitochondrial DNA copy number (mtDNAcn), is one of the major regulations of mitochondrial function by a set of transacting elements, including mitochondrial DNA polymerase gamma (POLG), working on the mtDNA control region. In this study, we investigated the mtDNAcn and the methylation status at both mtDNA control and POLGA promoter regions in human blood cells from individuals with a wide range of ages. A total of 119 blood samples were collected, including 24 umbilical cord blood samples from newborns and 95 peripheral blood samples from individuals aged 18 to 96 years. We observed an increase in mtDNAcn, as well as a rise in the methylation levels of the mtDNA control region during aging, particularly in subjects aged ≥ 45. In addition, a positive correlation was also found between the methylation levels of the 4th CpG site in the POLGA promoter region and mtDNAcn during aging. These results suggest epigenetic regulation at mitochondrial and nuclear genes for mitochondrial biogenesis during aging in human blood cells.

Graphical abstract