QUALITATIVE AND QUANTITATIVE CHANGES IN SKELETAL-MUSCLE MTDNA AND EXPRESSION OF MITOCHONDRIAL-ENCODED GENES IN THE HUMAN AGING PROCESS

It has been widely postulated that age-dependent changes in the mitoch ondrial genetic system may contribute to the human aging process. We r ecently reported unchanged specific activities of mitochondrial respir atory chain enzymes and a decrease in oxidation capacity of different substrates with aging, due, in part, to some confounding variables suc h as physical activity or tobacco consumption. The present study deals with age-related changes in muscle mtDNA structure and its biogenesis in humans. We found a low prevalence of mtDNA rearrangements with agi ng, only detected by PCR. The mtDNA content increased significantly wi th age (b = 0.0115, P < 0.0001), Also, an unchanged steady-state level of mitochondrial transcripts, a reduced transcription rate (P < 0.000 1), and an increase in mitochondrial membrane lipid peroxidation (P < 0.0001) were observed in aging, These data demonstrate that minor stru ctural mtDNA changes appear during the human aging process, By contras t, alterations in mitochondrial homeostasis ultimately producing modif ications in mitochondrial biogenesis rates could play a role in the pr ocess of human senescence. (C) 1997 Academic Press.