title: The 4977 bp deletion of mitochondrial DNA in human skeletal muscle, heart and different areas of the brain: a useful biomarker or more?
abstract: It has been suggested that deletions of mitochondrial DNA (mtDNA) are important players with regard to the ageing process. Since the early 1990s, the 4977 bp deletion has been studied in various tissues, especially in postmitotic tissues with high energy demand. Unfortunately, some of these studies included less than 10 subjects, so the aim of our study was to quantify reliably the deletion amount in nine different regions of human brain, heart and skeletal muscle in a cohort of 92 individuals. The basal ganglia contain the highest deletion amounts with values up to 2.93% and differences in deletion levels between early adolescence and older ages were up to three orders of magnitude. Values in frontal lobe were on average an order of magnitude lower, but lowest in cerebellar tissue where the amount was on average only 5 x 10(-3) of the basal ganglia. The deletion started to accumulate in iliopsoas muscle early in the fourth decade of life with values between 0.00019% and 0.0035% and was highest in a 102-year-old woman with 0.14%. In comparison to skeletal muscle, the overall abundance in heart muscle of the left ventricle was only one-third. The best linear logarithmic correlation between amount of the deletion and age was found in substantia nigra with r=0.87 (p<0.0005) followed by anterior wall of the left ventricle (r=0.82; p<0.0005). With regard to mitochondrial DNA damage, we propose to use the 4977 bp deletion as an ideal biomarker to discriminate between physiological ageing and accelerated ageing. The biological meaning of mitochondrial deletions in the process of ageing is under discussion, but there is experimental evidence that large-scale deletions impair the oxidative phosphorylation in single cells and sensitize these cells to undergo apoptosis.
authors.affiliation: Department of Legal Medicine, University Hospital Schleswig-Holstein-Campus Luebeck, Kahlhorststrasse 31-35, 23562 Lübeck, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Meissner
authors.affiliation: Medizinische Klinik II, University Hospital Schleswig-Holstein-Campus Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Bruse
authors.affiliation: Department of Cardiac Surgery, University Hospital Schleswig-Holstein-Campus Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany.
authors.forename: Salaheldien Ali
authors.initials: SA
authors.lastname: Mohamed
authors.affiliation: Department of Legal Medicine, University Hospital Schleswig-Holstein-Campus Luebeck, Kahlhorststrasse 31-35, 23562 Lübeck, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Schulz
authors.affiliation: Department of Legal Medicine, University Hospital Schleswig-Holstein-Campus Luebeck, Kahlhorststrasse 31-35, 23562 Lübeck, Germany.
authors.forename: Hanne
authors.initials: H
authors.lastname: Warnk
authors.affiliation: Department of Molecular Medicine and Pathology, School of Medical Sciences, The University of Auckland, P.O. Box 92019, Auckland, New Zealand.
authors.forename: Thilo
authors.initials: T
authors.lastname: Storm
authors.affiliation: Department of Legal Medicine, University Hospital Schleswig-Holstein-Campus Luebeck, Kahlhorststrasse 31-35, 23562 Lübeck, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Oehmichen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics; D001923:Brain Chemistry; D002648:Child; D002675:Child, Preschool; D004272:DNA, Mitochondrial / Q000235:genetics*; D005819:Genetic Markers; D006801:Humans; D007223:Infant; D008875:Middle Aged; D008929:Mitochondria, Heart / Q000235:genetics; D008931:Mitochondria, Muscle / Q000235:genetics; D018482:Muscle, Skeletal / Q000737:chemistry*; D009206:Myocardium / Q000737:chemistry*; D016133:Polymerase Chain Reaction / Q000379:methods; D017384:Sequence Deletion
chemical_list: D004272:DNA, Mitochondrial; D005819:Genetic Markers