A. Barrientos et al., QUALITATIVE AND QUANTITATIVE CHANGES IN SKELETAL-MUSCLE MTDNA AND EXPRESSION OF MITOCHONDRIAL-ENCODED GENES IN THE HUMAN AGING PROCESS, Biochemical and molecular medicine, 62(2), 1997, pp. 165-171
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.