AGE-DEPENDENT INCREASE OF MITOCHONDRIAL-DNA DELETIONS TOGETHER WITH LIPID PEROXIDES AND SUPEROXIDE-DISMUTASE IN HUMAN LIVER-MITOCHONDRIA

We previously reported an age-dependent deterioration of mitochondrial respiration as well as two age-associated mitochondrial DNA (mtDNA) deletions in the human liver. In this study, we further determined the relative quantities of the deleted mtDNAs in liver biopsies from 64 subjects of different ages. The results showed that both mtDNA deletions increase in frequency and quantity with age. Moreover, we measured hepatic lipid peroxides (malondialdehyde; MDA) of isolated mitochondria and manganese superoxide dismutase (Mn-SOD) activity of submitochondrial particles. We found a significant age-dependent increase in both MDA and Mn-SOD levels in liver mitochondria. These results confirm the previous contention that enhanced generation of lipid peroxides in the mitochondria during the aging process may damage mtDNA, and mtDNA deletions may be one of the important factors contributing to aging in humans.