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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2006-8-15
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pubmed:abstractText |
Skeletal muscle-mass loss with age has severe health consequences, yet the molecular basis of the loss remains obscure. Although mitochondrial DNA (mtDNA)-deletion mutations have been shown to accumulate with age, for these aberrant genomes to be physiologically relevant, they must accumulate to high levels intracellularly and be present in a significant number of cells. We examined mtDNA-deletion mutations in vastus lateralis (VL) muscle of human subjects aged 49-93 years, using both histologic and polymerase-chain-reaction (PCR) analyses, to determine the physiological and genomic integrity of mitochondria in aging human muscle. The number of VL muscle fibers exhibiting mitochondrial electron-transport-system (ETS) abnormalities increased from an estimated 6% at age 49 years to 31% at age 92 years. We analyzed the mitochondrial genotype of 48 single ETS-abnormal, cytochrome c oxidase-negative/succinate dehydrogenase-hyperreactive (COX-/SDH++) fibers from normal aging human subjects and identified mtDNA-deletion mutations in all abnormal fibers. Deletion mutations were clonal within a fiber and concomitant to the COX-/SDH++ region. Quantitative PCR analysis of wild-type and deletion-containing mtDNA genomes within ETS-abnormal regions of single fibers demonstrated that these deletion mutations accumulate to detrimental levels (>90% of the total mtDNA).
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/16909385-10325435,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16909385-10894897,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16909385-10968778,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16909385-11156948,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16909385-11691938,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16909385-12015381,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16909385-12031622,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16909385-12136116,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16909385-12673356,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16909385-1383754,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16909385-1424481,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16909385-1469460,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16909385-14734641,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16909385-14734642,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16909385-1502147,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16909385-15164064,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16909385-15280047,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16909385-15379855,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16909385-1551433,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16909385-16604072,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16909385-1965280,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16909385-1996112,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16909385-2163769,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16909385-2263455,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16909385-3379447,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16909385-3427464,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16909385-4300067,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16909385-6318426,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16909385-6617027,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16909385-7479075,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16909385-7679851,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16909385-7818253,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16909385-7993927,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16909385-8077182,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16909385-8373427,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16909385-8569289,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16909385-8612095,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16909385-8630698,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16909385-9164280,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16909385-9485063,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16909385-9554417,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16909385-9700705,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16909385-9840742
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0002-9297
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
79
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
469-80
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:16909385-Aged,
pubmed-meshheading:16909385-Aged, 80 and over,
pubmed-meshheading:16909385-Aging,
pubmed-meshheading:16909385-DNA, Mitochondrial,
pubmed-meshheading:16909385-Electron Transport,
pubmed-meshheading:16909385-Electron Transport Chain Complex Proteins,
pubmed-meshheading:16909385-Electron Transport Complex IV,
pubmed-meshheading:16909385-Female,
pubmed-meshheading:16909385-Humans,
pubmed-meshheading:16909385-Male,
pubmed-meshheading:16909385-Middle Aged,
pubmed-meshheading:16909385-Mitochondria, Muscle,
pubmed-meshheading:16909385-Muscle, Skeletal,
pubmed-meshheading:16909385-Muscle Fibers, Skeletal,
pubmed-meshheading:16909385-Sequence Deletion,
pubmed-meshheading:16909385-Succinate Dehydrogenase
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pubmed:year |
2006
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pubmed:articleTitle |
Mitochondrial DNA-deletion mutations accumulate intracellularly to detrimental levels in aged human skeletal muscle fibers.
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pubmed:affiliation |
Department of Animal Health and Biomedical Sciences, University of Wisconsin, Madison, WI 53706, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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