Age-related mitochondrial genotypic and phenotypic alterations in human skeletal muscle

To have a clearer picture of how mitochondrial damages are associated to aging, a comprehensive study of phenotypic and genotypic alterations was carried out, analyzing with histochemical and molecular biology techniques the same skeletal muscle specimens of a large number of healthy subjects from 1...

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Published in:Free radical biology & medicine 2001-06, Vol.30 (11), p.1223-1233
Main Authors: Pesce, V, Cormio, A, Fracasso, F, Vecchiet, J, Felzani, G, Lezza, A M, Cantatore, P, Gadaleta, M N
Format: Article
Language:English
Subjects:
Adolescent
Adult
Aged
Aged, 80 and over
Aging - physiology
DNA, Mitochondrial - genetics
Electron Transport Complex IV - metabolism
Female
Gene Rearrangement - physiology
Genotype
Humans
Immunoenzyme Techniques
Male
Middle Aged
Mitochondria, Muscle - genetics
Muscle Fibers, Skeletal - enzymology
Muscle, Skeletal - cytology
Muscle, Skeletal - metabolism
Phenotype
Polymerase Chain Reaction - methods
Sequence Deletion
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Summary:To have a clearer picture of how mitochondrial damages are associated to aging, a comprehensive study of phenotypic and genotypic alterations was carried out, analyzing with histochemical and molecular biology techniques the same skeletal muscle specimens of a large number of healthy subjects from 13 to 92 years old. Histochemical data showed that ragged red fibers (RRF) appear at about 40 years of age and are mostly cytochrome c oxidase (COX)-positive, whereas they are almost all COX-negative thereafter. Molecular analyses showed that the 4977 bp deletion of mitochondrial DNA (mtDNA(4977)) and the 7436 bp deletion of mtDNA (mtDNA(7436)) are already present in individuals younger than 40 years of age, but their occurrence does not change with age. After 40 years of age the number of mtDNA deleted species, as revealed by Long Extension PCR (LX-PCR), increases, the 10422 bp deletion of mtDNA (mtDNA(10422)) appears, although with a very low frequency of occurrence, and mtDNA content is more than doubled. Furthermore, mtDNA(4977) level directly correlates with that of COX-negative fibers in the same analyzed subjects. These data clearly show that, after 40 years of age, the phenotypic and genotypic mitochondrial alterations here studied appear in human skeletal muscle and that they are closely related.
ISSN:0891-5849
DOI:10.1016/s0891-5849(01)00517-2