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The age‐associated decrease in the amount of amplifiable full‐length mitochondrial DNA in human skeletal muscle
Author(s) -
Kovalenko Sergey A.,
Kopsidas George,
Islam Mohammed M.,
Heffernan Damien,
Fitzpatrick Jennifer,
Caragounis Aphrodite,
Gingold Elliot,
Linnane Anthony W.
Publication year - 1998
Publication title -
iubmb life
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.132
H-Index - 113
eISSN - 1521-6551
pISSN - 1521-6543
DOI - 10.1080/15216549800204802
Subject(s) - mitochondrial dna , biology , cytochrome c oxidase , skeletal muscle , microbiology and biotechnology , gene , blot , mitochondrion , dna , southern blot , genetics , polymerase chain reaction , endocrinology
There has been a continuous evolution in our concept [1] that mtDNA undergoes a range of mutations with age and that such alterations lead to a decline in mitochondrial bioenergy capacity. Here we report that a wide range of deletion mutations accumulate with age and the amount of full‐length mtDNA (FLmtDNA) amplifiable by extra‐long PCR (XL‐PCR) markedly decreases with age. An analysis of single human quadriceps muscle fibres reveals a close correlation between the decrease in FLmtDNA and the decline in cytochrome c oxidase activity, an exemplifier of mitochondrial bioenergy. However, Southern blotting analysis of unamplified genomic DNA shows that there is little decrease in FLmtDNA in aged quadriceps. The results are interpreted to indicate that while there is little change in the total mtDNA with age, nonetheless a significant proportion of this mtDNA is extensively damaged such that it cannot be amplified by XL‐PCR. The amplifiable FLmtDNA, which putatively represents the functional component of the mtDNA, decreases markedly with age.