PMID- 10098461
OWN - NLM
STAT- MEDLINE
DCOM- 19990521
LR  - 20191210
IS  - 1071-5762 (Print)
IS  - 1029-2470 (Linking)
VI  - 29
IP  - 6
DP  - 1998 Dec
TI  - Age-associated change in mitochondrial DNA damage.
PG  - 573-9
AB  - There is an age-associated decline in the mitochondrial function of the Wistar 
      rat heart. Previous reports from this lab have shown a decrease in mitochondrial 
      cytochrome c oxidase (COX) activity associated with a reduction in COX gene and 
      protein expression and a similar decrease in the rate of mitochondrial protein 
      synthesis. Damage to mitochondrial DNA may contribute to this decline. Using the 
      HPLC-Coularray system (ESA, USA), we measured levels of nuclear and mitochondrial 
      8-oxo-2'-deoxyguanosine (8-oxodG) from 6-month (young) and 23-month-old 
      (senescent) rat liver DNA. We measured the sensitivity of the technique by 
      damaging calf thymus DNA with photoactivated methylene blue for 30s up to 2h. The 
      levels of damage were linear over the entire time course including the shorter 
      times which showed levels comparable to those expected in liver. For the liver 
      data, 8-oxodG was reported as a fraction of 2-deoxyguanosine (2-dG). There was no 
      change in the levels of 8-oxodG levels in the nuclear DNA from 6 to 23-months of 
      age. However, the levels of 8-oxodG increased 2.5-fold in the mitochondrial DNA 
      with age. At 6 months, the level of 8-oxodG in mtDNA was 5-fold higher than 
      nuclear and increased to approximately 12-fold higher by 23 months of age. These 
      findings agree with other reports showing an age-associated increase in levels of 
      mtDNA damage; however, the degree to which it increases is smaller. Such damage 
      to the mitochondrial DNA may contribute to the age-associated decline in 
      mitochondrial function.
FAU - Hudson, E K
AU  - Hudson EK
AD  - Laboratory of Molecular Genetics, Gerontology Research Center, NIA, NIH, 
      Baltimore, MD 21224-6823, USA.
FAU - Hogue, B A
AU  - Hogue BA
FAU - Souza-Pinto, N C
AU  - Souza-Pinto NC
FAU - Croteau, D L
AU  - Croteau DL
FAU - Anson, R M
AU  - Anson RM
FAU - Bohr, V A
AU  - Bohr VA
FAU - Hansford, R G
AU  - Hansford RG
LA  - eng
PT  - Journal Article
PL  - England
TA  - Free Radic Res
JT  - Free radical research
JID - 9423872
RN  - 88847-89-6 (8-Hydroxy-2'-Deoxyguanosine)
RN  - 9007-49-2 (DNA)
RN  - EC 1.9.3.1 (Electron Transport Complex IV)
RN  - EC 3.1.- (Endodeoxyribonucleases)
RN  - EC 3.1.25.- (mitochondrial oxidative damage endonuclease)
RN  - G9481N71RO (Deoxyguanosine)
SB  - IM
MH  - 8-Hydroxy-2'-Deoxyguanosine
MH  - Age Factors
MH  - Animals
MH  - DNA/isolation & purification
MH  - *DNA Damage/drug effects/radiation effects
MH  - Deoxyguanosine/analogs & derivatives/analysis
MH  - Electron Transport Complex IV/metabolism
MH  - Endodeoxyribonucleases/metabolism
MH  - Gene Expression Regulation
MH  - Mitochondria, Liver/*genetics/metabolism
MH  - Protein Biosynthesis
MH  - Rats
EDAT- 1999/03/31 00:00
MHDA- 1999/03/31 00:01
CRDT- 1999/03/31 00:00
PHST- 1999/03/31 00:00 [pubmed]
PHST- 1999/03/31 00:01 [medline]
PHST- 1999/03/31 00:00 [entrez]
AID - 10.1080/10715769800300611 [doi]
PST - ppublish
SO  - Free Radic Res. 1998 Dec;29(6):573-9. doi: 10.1080/10715769800300611.