1992
DOI: 10.1016/0921-8734(92)90016-i
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Progressive loss of cytochrome c oxidase in the human extraocular muscles in ageing — a cytochemical-immunohistochemical study

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Cited by 107 publications
(45 citation statements)
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“…Once the mutation appears, it is selectively amplified until it comes to be the predominate mtDNA in the cell or fiber domain of origin. This idea has been substantiate by in situ hybridization to mtDNAs within individual muscle fibers from the elderly which revealed the clonal amplification of different mtDNA rearrangements in different regions of the same muscle fiber (11), and by studying cultured cardiomyocytes which revealed that each cardiomyocyte harbored only one mtDNA rearrangement that was clonally expanded within that cell (12,13). Thus, each somatic mtDNA rearrangement reaches high levels of heteroplasmy within its cell of origin, however, when a tissue is homogenized, all of the rearranged mtDNA are mixed together diluting each of the molecules to low average levels.…”
mentioning
confidence: 86%
“…Once the mutation appears, it is selectively amplified until it comes to be the predominate mtDNA in the cell or fiber domain of origin. This idea has been substantiate by in situ hybridization to mtDNAs within individual muscle fibers from the elderly which revealed the clonal amplification of different mtDNA rearrangements in different regions of the same muscle fiber (11), and by studying cultured cardiomyocytes which revealed that each cardiomyocyte harbored only one mtDNA rearrangement that was clonally expanded within that cell (12,13). Thus, each somatic mtDNA rearrangement reaches high levels of heteroplasmy within its cell of origin, however, when a tissue is homogenized, all of the rearranged mtDNA are mixed together diluting each of the molecules to low average levels.…”
mentioning
confidence: 86%
“…For example, polymerase chain reaction (PCR) experiments have shown that skeletal muscle from human subjects under the age of 40 contains primarily intact mtDNAs, whereas skeletal muscle from subjects over the age of 50 shows an accumulation of a wide array of mtDNA rearrangements (69). In addition, the skeletal muscle of elderly subjects has been found to have RRFs, with each COX Ϫ and SDH ϩ fiber containing a different mtDNA mutation (3,70). This confirms that each of the mutations arose de novo and was selectively amplified within the cell to create the www.sciencemag.org SCIENCE VOL 283 5 MARCH 1999 regional respiratory defects.…”
Section: Somatic Mtdna Mutations In Aging and Cancermentioning
confidence: 99%
“…Although these studies identified, in numerous species, an ageassociated accumulation of mtDNA deletion mutations, an association between genotype and phenotype was not possible due to the heterogeneous distribution of the abnormalities in aged tissue. In situ hybridization studies (Muller-Hoecker, 1990;Muller-Hoecker et al ., 1992Lee et al ., 1998;Lopez et al ., 2000) determined that mtDNA deletion mutations and associated enzymatic abnormalities were distributed in a mosaic pattern in aged muscle. In addition, the abnormalities are segmental, contained within a portion of the affected muscle fiber.…”
Section: Introductionmentioning
confidence: 99%