title: Mitochondrial gene mutation: the ageing process and degenerative diseases.
abstract: Polymerase chain reaction (PCR) amplification was carried out on total DNA from a range of autopsy tissues from deceased human subjects with no known mitochondrial disease, aged from birth (80 minutes) to 87 years. We report the finding of an age-related 5 kb deletion in the mitochondrial genomes of these subjects. The deletion occurs between nucleotide positions 8470 and 13459 of the mitochondrial genome, and is flanked by a 13 bp direct repeat. All tissues from adult subjects showed the presence of mitochondrial DNA molecules with the deletion after a 30 cycle PCR amplification; by contrast the deletion was not similarly detected in any of the infant tissues analysed. However, the occurrence of the deletion was detected in the infant tissues after 60 PCR cycles of MtDNA amplification. It is concluded that such deletions are not necessarily associated with particular mitochondrial diseases but occur naturally, and with increasing frequency with age. A consequence of the accumulation of this deletion could be a progressive decrease with age of bioenergetic capacity which in turn could influence the rate of ageing and predispose to age-associated degenerative diseases.
authors.affiliation: Centre for Molecular Biology and Medicine, Monash University, Clayton, Victoria, Australia.
authors.forename: A W
authors.initials: AW
authors.lastname: Linnane
authors.forename: A
authors.initials: A
authors.lastname: Baumer
authors.forename: R J
authors.initials: RJ
authors.lastname: Maxwell
authors.forename: H
authors.initials: H
authors.lastname: Preston
authors.forename: C F
authors.initials: CF
authors.lastname: Zhang
authors.forename: S
authors.initials: S
authors.lastname: Marzuki
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics*; D001483:Base Sequence; D002872:Chromosome Deletion; D004272:DNA, Mitochondrial / Q000235:genetics*; D003576:Electron Transport Complex IV / Q000235:genetics; D004587:Electrophoresis, Agar Gel; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D009247:NADH, NADPH Oxidoreductases / Q000235:genetics; D016133:Polymerase Chain Reaction; D012091:Repetitive Sequences, Nucleic Acid
chemical_list: D004272:DNA, Mitochondrial; D009247:NADH, NADPH Oxidoreductases; D003576:Electron Transport Complex IV; D000251:Adenosine Triphosphatases