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Differential occurrence of mutations in mitochondrial DNA of human skeletal muscle during aging
Author(s) -
Zhang Chunfang,
Liu Vincent W. S.,
Addessi Corrado L.,
Sheffield David A.,
Linnane Anthony W.,
Nagley Phillip
Publication year - 1998
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/(sici)1098-1004(1998)11:5<360::aid-humu3>3.0.co;2-u
Subject(s) - biology , mitochondrial dna , skeletal muscle , point mutation , genetics , mutation , microbiology and biotechnology , mutant , gene , medicine , endocrinology
Seven mtDNA mutations (five base substitutions and two deletions) were studied in skeletal muscle samples of 18 human subjects aged 1 hr to 90 years. Quantitative PCR procedures were applied to determine the incidence (frequency of occurrence) and abundance (percentage of mutant mtDNA out of total mtDNA). The base substitutions, in general, showed a very early onset, three such mutations being detectable in the muscles of infants aged 1 hr and 5 weeks. Of two disease‐associated point mutations studied, 3243 A→G showed significant accumulation with age ( P < 0.05), while 8993 T→G showed no significant age accumulation ( P > 0.1). Moreover, three arbitrarily chosen mutations (not disease‐associated) showed no age‐associated accumulation: two (7029 C→T and 7920 A→G) showed little change over the years ( P > 0.1), while the other (13167 A→G) showed a significant decrease ( P < 0.05). Both the 4,977‐bp and 7,436‐bp deletions showed a significant age‐associated occurrence ( P < 0.01 and P < 0.05, respectively). The age of onset of detectable deletions is about 20–40 years; thereafter, the incidence and abundance of deletions tend to increase as a function of advancing age. The seven specific mutations were found to occur independent of each other, indicating the random nature of mtDNA mutations in skeletal muscle. Moreover, the age‐associated accumulation of multiple deletions was observed in the same set of muscle tissues, each extract displaying a unique set of multiple PCR products. Thus, mutations in mtDNA occur differentially in human skeletal muscle during aging. Hum Mutat 11:360–371, 1998. © 1998 Wiley‐Liss, Inc.