Age-related extensive fragmentation of mitochondrial DNA into minicircles

Biochem Biophys Res Commun. 1996 Sep 13;226(2):369-77. doi: 10.1006/bbrc.1996.1363.

Abstract

In normal human hearts, a progressive age-related fragmentation of mitochondrial (mt) DNA into various-sized deleted (delta) mtDNA up to 358 types was documented by a novel total-detection system for deletions. The delta mtDNA lacking replication origin(s), minicircles, accumulated up to 280 types out of the 358, suggesting a yet unknown replication mechanism in human. Wild-type mtDNA decreased linearly down to 11% of the total with age negatively correlated with delta mtDNA and oxidized nucleoside, 8-hydroxydeoxyguanosine. A remarkable mirror image observed in delta mtDNA size distribution as well implies that random hydroxyl-radical attacks resulted in double-strand break and rejoining of mtDNA as a preferable mechanism to form various delta mtDNA of closed circular duplex. These facts support the 'redox mechanism of aging.'

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Aging / genetics*
  • Child
  • Child, Preschool
  • DNA, Circular / genetics*
  • DNA, Mitochondrial / chemistry
  • DNA, Mitochondrial / genetics*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Polymerase Chain Reaction

Substances

  • DNA, Circular
  • DNA, Mitochondrial