|Budget Amount *help
¥2,100,000 (Direct Cost : ¥2,100,000)
Fiscal Year 1993 : ¥800,000 (Direct Cost : ¥800,000)
Fiscal Year 1992 : ¥1,300,000 (Direct Cost : ¥1,300,000)
1. Age-associated damage in mitochondrial DNA(mtDNA)in human hearts ; Mitochondrial DNA specimens from post-mortem human heart muscles of subjects in differing age groups were hydrolyzed. 8-Hydroxy-deoxyguanosine(8-OH-dG), a hydroxyl-radical adduct of deoxyguanosine, in mtDNA was quantitatively determined using a micro high-performance-liquid-chromatorgaphy/mass spectrometry system. In each specimen, the mtDNA with a 7.4 kilo base-pair deletion was quantified by the kinetic PCR method. In association with age, the 8-OH-dG content accumulated exponentially up to 1.5% with a correlative increase in the content of the deleted mtDNA up to 7%. There was a clear correlation between the 8-OH-dG content and the population of mtDNA with deletion(r=0.93, P<0.01).
2. Changes in skeletal muscle, hert and liver mitochondrial electron transport activities in rats and dogs of various ages. ; We determined skeletal muscle, heart and liver mitochondrial electron transport activities in rats and dogs of
various ages. The activity of complex I was the most susceptible to aging among the activities of complexes. Skeletal muscle mitochondria were the most susceptible to aging among the tissues, and heart mitochondria were second susceptible. Liver was the most stable organ to aging. Involvement of mitochondria in the development of age-associated declines in cellular function is especially emphasized in post mitotic cells, and age-associated mitochondrial functional changes are stressed in mitochondrial complexes that contain mitochondrial DNA-encoded subunits.
3. Animal model of mitochondrial disease ; Tow kinds of drugs were used to two animal models of mitochondrial disease, i.e., AZT, which was reported to cause mitochondrial disease in many AIDS patients, and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, a potent mutagenic agent produced during thermal processing of meats. We measured mitochondrial respiratory activities, and the amounts of 8-OH-dG and deletions in mtDNA.As a result, AZT as well as 2-amino-1-methyl-6-phnylimidazo[4,5-b]pyridine, induced he decline in mitochondrial function, and accelerated the accumulation of 8-OH-dG and deletions in mtDNA. Less