TY - JOUR
T1 - Mitochondrial DNA deletions and differential mitochondrial DNA content in Rhesus monkeys
T2 - Implications for aging
AU - Mao, Peizhong
AU - Gallagher, Patience
AU - Nedungadi, Samira
AU - Manczak, Maria
AU - shirendeb, Ulziibat P.
AU - Kohama, Steven G.
AU - Ferguson, Betsy
AU - Park, Byung S.
AU - Reddy, P. Hemachandra
N1 - Funding Information:
This research presented was supported by NIH grants AG028072, RR00163 and Alzheimer Association IIRG grant, IIRG-09-92429
PY - 2012/2
Y1 - 2012/2
N2 - The purpose of this study was to determine the relationship between mitochondrial DNA (mtDNA) deletions, mtDNA content and aging in rhesus monkeys. Using 2 sets of specific primers, we amplified an 8. kb mtDNA fragment covering a common 5.7. kb deletion and the entire 16.5. kb mitochondrial genome in the brain and buffy-coats of young and aged monkeys. We studied a total of 66 DNA samples: 39 were prepared from a buffy-coat and 27 were prepared from occipital cortex tissues. The mtDNA data were assessed using a permutation test to identify differences in mtDNA, in the different monkey groups. Using real-time RT-PCR strategy, we also assessed both mtDNA and nuclear DNA levels for young, aged and male and female monkeys. We found a 5.7. kb mtDNA deletion in 81.8% (54 of 66) of the total tested samples. In the young group of buffy-coat DNA, we found 5.7. kb deletions in 7 of 17 (41%), and in the aged group, we found 5.7. kb deletions in 12 of 22 (54%), suggesting that the prevalence of mtDNA deletions is related to age. We found decreased mRNA levels of mtDNA in aged monkeys relative to young monkeys. The increases in mtDNA deletions and mtDNA levels in aged rhesus monkeys suggest that damaged DNA accumulates as rhesus monkeys age and these altered mtDNA changes may have physiological relevance to compensate decreased mitochondrial function.
AB - The purpose of this study was to determine the relationship between mitochondrial DNA (mtDNA) deletions, mtDNA content and aging in rhesus monkeys. Using 2 sets of specific primers, we amplified an 8. kb mtDNA fragment covering a common 5.7. kb deletion and the entire 16.5. kb mitochondrial genome in the brain and buffy-coats of young and aged monkeys. We studied a total of 66 DNA samples: 39 were prepared from a buffy-coat and 27 were prepared from occipital cortex tissues. The mtDNA data were assessed using a permutation test to identify differences in mtDNA, in the different monkey groups. Using real-time RT-PCR strategy, we also assessed both mtDNA and nuclear DNA levels for young, aged and male and female monkeys. We found a 5.7. kb mtDNA deletion in 81.8% (54 of 66) of the total tested samples. In the young group of buffy-coat DNA, we found 5.7. kb deletions in 7 of 17 (41%), and in the aged group, we found 5.7. kb deletions in 12 of 22 (54%), suggesting that the prevalence of mtDNA deletions is related to age. We found decreased mRNA levels of mtDNA in aged monkeys relative to young monkeys. The increases in mtDNA deletions and mtDNA levels in aged rhesus monkeys suggest that damaged DNA accumulates as rhesus monkeys age and these altered mtDNA changes may have physiological relevance to compensate decreased mitochondrial function.
KW - Aging
KW - Mitochondrial DNA
KW - Mitochondrial DNA deletion
KW - Mitochondrial-encoded DNA
KW - Real-time RT-PCR
KW - Rhesus monkeys
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U2 - 10.1016/j.bbadis.2011.10.014
DO - 10.1016/j.bbadis.2011.10.014
M3 - Article
C2 - 22056405
AN - SCOPUS:83055168354
SN - 0925-4439
VL - 1822
SP - 111
EP - 119
JO - Biochimica et Biophysica Acta - Molecular Basis of Disease
JF - Biochimica et Biophysica Acta - Molecular Basis of Disease
IS - 2
ER -