Age-related extensive fragmentation of mitochondrial DNA into minicircles

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.'