Biological rule of mitochondrial structure and function in relation to mtDNA deletion during brain aging of senescent mice

Aim: To study the changes of mitochondria isolated from the brain of aged mice, and probe into the senescent mechanism. Methods: The experiment was finished in the Scientific Experiment Center of Guangzhou Physical Education and Medical College of Sun Yat-sen University from January 2002 to April 2003. Morphometric quantitative study of mitochondria in myocardium was investigated with electron microscopy, the activities of cytochrome C oxidase and activities of nicotinamide-adenine dinucleotide(NADH) dehydrognase in respiratory chain were measured with Clark oxygen electrode, the activities of antioxidant enzyme were measured with spectrophotography, the levels of mtDNA 3 866 bp deletion were determined with polymerase chain reaction(PCR). Results: The decreased quantity of mitochondrion, RCR, activities of NADH dehydrognase and cytochrome oxidase and increased volum of brain mitochondria and activities of antioxidant enzyme were found in 20-month aged mice as compared with 5-month mice, meanwhile, the mtDNA 3 866 bp deletion was increased, and there was no significant difference in ADP/O. Correlated analysis to all indexes, it was found that RCR and mtDNA deletion were significantly correlated(r = 0.739, P < 0.01), and so between the NADH dehydrognase, activities of cytochrome C oxidase and mtDNA deletion(r = 0.582, P < 0.05. r = 0.810, P < 0.01), but it was not between antioxidant enzyme and mtDNA deletion(r = 0.256, P > 0.05). Conclusion: These observations suggest that accumulation of mtDNA damage causes the decreased activities of enzyme compound, hypofunction of respiratory chain when senility, and those may be the foundation of onset of aging regressive disease and organism senility.