Age-related extensive fragmentation of mitochondrial DNA into minicircles.
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.'
Hayakawa
M
M
Department of Biomedical Chemistry, Faculty of Medicine, University of Nagoya, Japan.
Katsumata
K
K
Yoneda
M
M
Tanaka
M
M
Sugiyama
S
S
Ozawa
T
T
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004270:DNA, Circular / Q000235:genetics*; D004272:DNA, Mitochondrial / Q000737:chemistry / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction
D004270:DNA, Circular; D004272:DNA, Mitochondrial