title: Mitochondrial DNA mutations in RRF of healthy subjects of different age.
abstract: To obtain information on the mechanisms responsible of the generation of ragged red fibers (RRF) during aging, we analyzed the mitochondrial genotype of single skeletal muscle fibers of healthy individuals having an age comprised between 45 and 92 years. The sequencing of the D-loop region showed many sequence changes with respect to the Cambridge reference sequence (CRS), in both RRF and normal fibers. These changes were more abundant in RRF and their number increased between 50 and 60, and 61 and 70 years and then remained approximately constant. The analysis of the sequence changes showed that each subject contained one or more changes associated to RRF in positions of D-loop region that either do not change or that change very rarely. In general the same type of RRF-associated change was not found in more than one individual; exceptions were changes in positions 189, 295, 374 and 514, detected in 20-50% of analyzed subjects. In particular the A189G age-associated mutation was found only in old individuals and prevalently in RRF. Sequencing of other two mtDNA regions showed no relevant changes in the 16S/ND1 region and two RRF-associated original mutations, G5847A and A5884C, in two very conserved positions of tRNATyr. These results indicate that each subject has its own pattern of RRF-associated mutations in both coding and non-coding region of human mtDNA.
authors.affiliation: Dipartimento di Biochimica e Biologia Molecolare, Università degli Studi di Bari, Via Orabona, 4, 70125 Bari, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Cormio
authors.forename: Francesco
authors.initials: F
authors.lastname: Milella
authors.forename: Jacopo
authors.initials: J
authors.lastname: Vecchiet
authors.forename: Giorgio
authors.initials: G
authors.lastname: Felzani
authors.forename: Maria Nicola
authors.initials: MN
authors.lastname: Gadaleta
authors.forename: Palmiro
authors.initials: P
authors.lastname: Cantatore
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology*; D001483:Base Sequence; D051545:Cyclooxygenase 1; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics*; D006801:Humans; D017243:MERRF Syndrome / Q000235:genetics*; D008565:Membrane Proteins; D008875:Middle Aged; D008931:Mitochondria, Muscle / Q000502:physiology*; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000378:metabolism*; D009154:Mutation; D010456:Peptides, Cyclic / Q000235:genetics; D016133:Polymerase Chain Reaction / Q000379:methods; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics; D012343:RNA, Transfer / Q000235:genetics; D013385:Succinate Dehydrogenase / Q000235:genetics
chemical_list: D004272:DNA, Mitochondrial; D008565:Membrane Proteins; D010456:Peptides, Cyclic; D012343:RNA, Transfer; D051545:Cyclooxygenase 1; C496511:PTGS1 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D013385:Succinate Dehydrogenase