Aging-dependent large accumulation of point mutations in the human mtDNA control region for replication.
Progressive damage to mitochondrial DNA (mtDNA) during life is thought to contribute to aging processes. However, this idea has been difficult to reconcile with the small fraction of mtDNA so far found to be altered. Here, examination of mtDNA revealed high copy point mutations at specific positions in the control region for replication of human fibroblast mtDNA from normal old, but not young, individuals. Furthermore, in longitudinal studies, one or more mutations appeared in an individual only at an advanced age. Some mutations appeared in more than one individual. Most strikingly, a T414G transversion was found, in a generally high proportion (up to 50 percent) of mtDNA molecules, in 8 of 14 individuals above 65 years of age (57 percent) but was absent in 13 younger individuals.
Michikawa
Y
Y
Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.
Mazzucchelli
F
F
Bresolin
N
N
Scarlato
G
G
Attardi
G
G
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics*; D002460:Cell Line; D002648:Child; D002675:Child, Preschool; D004249:DNA Damage; D004260:DNA Repair; D004261:DNA Replication / Q000235:genetics*; D004272:DNA, Mitochondrial / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D005333:Fetus; D005347:Fibroblasts; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008137:Longitudinal Studies; D008875:Middle Aged; D008928:Mitochondria / Q000235:genetics*; D009690:Nucleic Acid Conformation; D009692:Nucleic Acid Heteroduplexes; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011544:Pseudogenes
D004272:DNA, Mitochondrial; D009692:Nucleic Acid Heteroduplexes