title: Marked increase in the number and variety of mitochondrial DNA rearrangements in aging human skeletal muscle.
abstract: Several reports have shown that individual mitochondrial DNA (mtDNA) deletions accumulate with age. However, the overall extent of somatic mtDNA damage with age remains unclear. We have utilized full-length PCR to concurrently screen for multiple mtDNA rearrangements in total DNA extracted from skeletal muscle derived from physiologically normal individuals (n = 35). This revealed that both the number and variety of mtDNA rearrangements increases dramatically between young and old individuals (P < 0.0001). We further examined the mtDNA from both the younger and older subjects by Southern blot analysis and observed an age-related increase in mtDNA(s) comparable in size to mtDNA products unique to patients with known mtDNA deletions. These data imply that a wide spectrum of mtDNA rearrangements accumulate in old individuals, which correlates with the marked age related decrease in OXPHOS capacity observed in post-mitotic tissues.
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000235:genetics*; D004272:DNA, Mitochondrial / Q000737:chemistry / Q000235:genetics*; D015321:Gene Rearrangement / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D008970:Molecular Weight; D018482:Muscle, Skeletal / Q000502:physiology*; D016133:Polymerase Chain Reaction / Q000379:methods; D017384:Sequence Deletion
chemical_list: D004272:DNA, Mitochondrial