[The mitochondrial genome and aging].
There is a lot of evidence that age-associated alterations of the mitochondrial genome occur, especially in postmitotic tissues such as brain, heart and skeletal muscle. These alterations are supposed to be a result of an attack of free radicals generated as normal byproducts of oxidative phosphorylation and lead to damage of proteins, lipids, and DNA. The alterations of mtDNA include oxidative damage of base pairs, point mutations, large-scale deletions or duplications. The 4977 bp deletion or "common deletion" reveals an age-dependent accumulation in postmitotic tissues, but not in fast-dividing tissues such as blood cells. In addition, it is observed that a tissue-specific accumulation occurs with the highest abundance in the basal ganglia, followed by skeletal muscle, heart, and lowest in cerebellar tissue. Third, pathological alterations of specific tissue, like ischemia/reperfusion events, display a pronounced accumulation of the deletion compared to age-matched controls. Because there are many mtDNA mutations, further analysis of all alterations of mtDNA will elucidate its role in the phenomenon of aging. Despite some criticisms of this free radical theory of aging, there is a lot of experimental evidence to support the important role of mitochondria in organismal aging.
Meissner
C
C
Institut für Rechtsmedizin des Universitätsklinikums Lübeck Kahlhorststrasse 31-35 23562 Lübeck, Germany. meissner@rmed.mu-luebeck.de
Mohamed
S A
SA
von Wurmb
N
N
Oehmichen
M
M
D000368:Aged; D000818:Animals; D016922:Cellular Senescence / Q000235:genetics*; D002872:Chromosome Deletion; D004249:DNA Damage / Q000502:physiology*; D004272:DNA, Mitochondrial / Q000235:genetics*; D005609:Free Radicals; D006801:Humans; D018384:Oxidative Stress / Q000502:physiology; D017354:Point Mutation / Q000235:genetics
D004272:DNA, Mitochondrial; D005609:Free Radicals