title: Lack of age-related increase of mitochondrial DNA amount in brain, skeletal muscle and human heart.
abstract: During the ageing process, an increase of mitochondrial DNA (mtDNA) deletions and other mutations have been reported. These structural alterations of mtDNA are assumed to cause a reduction in the respiratory chain activity and may contribute to the ageing process. Therefore, the question arises if the accumulation of deleted mtDNA is compensated in vivo by an increase of mtDNA synthesis via a feedback mechanism. We designed two human mtDNA-specific oligonucleotide probes for quantitative mtDNA analysis of 5 different tissues from 50 individuals aged from 8 weeks to 93 years. The amount of mtDNA was approximately 1.1 +/- 0.5% (4617 +/- 2099 copies) in the caudate nucleus, 1.0 +/- 0.5% (4198 +/- 2099 copies) in the frontal lobe cortex, 0.3 +/- 0.2% (1259 +/- 840 copies) in the cerebellar cortex, 1.0 +/- 0.4% (4198 +/- 1679 copies) in skeletal muscle and 2.2+/-1.3% (9235 +/- 5457 copies) in heart muscle. We did not observe any significant change in the absolute copy number during ageing in five different tissues, and therefore, found no evidence for the postulated feedback mechanism. Our study indicates that mtDNA copy number is tissue-specific and depends on the energy demand of the tissue.
authors.affiliation: Department of Forensic Medicine, University of Luebeck, Kahlhorststrasse 31-35, 23562 Luebeck, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Frahm
authors.forename: Salaheldien A
authors.initials: SA
authors.lastname: Mohamed
authors.forename: Petra
authors.initials: P
authors.lastname: Bruse
authors.forename: Christine
authors.initials: C
authors.lastname: Gemünd
authors.forename: Manfred
authors.initials: M
authors.lastname: Oehmichen
authors.forename: Christoph
authors.initials: C
authors.lastname: Meissner
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology*; D001921:Brain / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D004272:DNA, Mitochondrial / Q000378:metabolism*; D018628:Gene Dosage; D006801:Humans; D007223:Infant; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D013223:Statistics as Topic
chemical_list: D004272:DNA, Mitochondrial