title: Differential occurrence of mutations in mitochondrial DNA of human skeletal muscle during aging.
abstract: Seven mtDNA mutations (five base substitutions and two deletions) were studied in skeletal muscle samples of 18 human subjects aged 1 hr to 90 years. Quantitative PCR procedures were applied to determine the incidence (frequency of occurrence) and abundance (percentage of mutant mtDNA out of total mtDNA). The base substitutions, in general, showed a very early onset, three such mutations being detectable in the muscles of infants aged 1 hr and 5 weeks. Of two disease-associated point mutations studied, 3243 A-->G showed significant accumulation with age (P < 0.05), while 8993 T-->G showed no significant age accumulation (P > 0.1). Moreover, three arbitrarily chosen mutations (not disease-associated) showed no age-associated accumulation: two (7029 C-->T and 7920 A-->G) showed little change over the years (P > 0.1), while the other (13167 A-->G) showed a significant decrease (P < 0.05). both the 4,977-bp and 7,436-bp deletions showed a significant age-associated occurrence (P < 0.01 and P < 0.05, respectively). The age of onset of detectable deletions is about 20-40 years; thereafter, the incidence and abundance of deletions tend to increase as a function of advancing age. The seven specific mutations were found to occur independent of each other, indicating the random nature of mtDNA mutations in skeletal muscle. Moreover, the age-associated accumulation of multiple deletions was observed in the same set of muscle tissues, each extract displaying a unique set of multiple PCR products. Thus, mutations in mtDNA occur differentially in human skeletal muscle during aging.
authors.affiliation: Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia.
authors.forename: C
authors.initials: C
authors.lastname: Zhang
authors.forename: V W
authors.initials: VW
authors.lastname: Liu
authors.forename: C L
authors.initials: CL
authors.lastname: Addessi
authors.forename: D A
authors.initials: DA
authors.lastname: Sheffield
authors.forename: A W
authors.initials: AW
authors.lastname: Linnane
authors.forename: P
authors.initials: P
authors.lastname: Nagley
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics*; D000483:Alleles; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D004272:DNA, Mitochondrial / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008875:Middle Aged; D008931:Mitochondria, Muscle / Q000235:genetics*; D018482:Muscle, Skeletal / Q000737:chemistry*; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion
chemical_list: D004272:DNA, Mitochondrial