TY - JOUR
T1 - Qualitative and quantitative changes in skeletal muscle mtDNA and expression of mitochondrial-encoded genes in the human aging process
AU - Barrientos, Antoni
AU - Casademont, Jordi
AU - Cardellach, Francesc
AU - Ardite, Esther
AU - Estivill, Xavier
AU - Urbano-Márquez, Alvaro
AU - Fernández-Checa, J. Carlos
AU - Nunes, Virginia
N1 - Funding Information:
We thank Helena Kruyer for her help with the manuscript. This work was supported by Grants DGICYT PB93-0019, CICYT SAF191-95, FIS94/1563, and CICYT SAF96-0027. X.E. and V.N. are supported by Servei CatalaÁ de la Salut, Generalitat de Catalunya.
PY - 1997/12
Y1 - 1997/12
N2 - It has been widely postulated that age-dependent changes in the mitochondrial genetic system may contribute to the human aging process. We recently reported unchanged specific activities of mitochondrial respiratory chain enzymes and a decrease in oxidation capacity of different substrates with aging, due, in part, to some confounding variables such 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 aging, only detected by PCR. The mtDNA content increased significantly with age (b = 0.0115, P < 0.0001). Also, an unchanged steady-state level of mitochondrial transcripts, a reduced transcription rate (P < 0.0001), and an increase in mitochondrial membrane lipid peroxidation (P < 0.0001) were observed in aging. These data demonstrate that minor structural mtDNA changes appear during the human aging process. By contrast, alterations in mitochondrial homeostasis ultimately producing modifications in mitochondrial biogenesis rates could play a role in the process of human senescence.
AB - It has been widely postulated that age-dependent changes in the mitochondrial genetic system may contribute to the human aging process. We recently reported unchanged specific activities of mitochondrial respiratory chain enzymes and a decrease in oxidation capacity of different substrates with aging, due, in part, to some confounding variables such 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 aging, only detected by PCR. The mtDNA content increased significantly with age (b = 0.0115, P < 0.0001). Also, an unchanged steady-state level of mitochondrial transcripts, a reduced transcription rate (P < 0.0001), and an increase in mitochondrial membrane lipid peroxidation (P < 0.0001) were observed in aging. These data demonstrate that minor structural mtDNA changes appear during the human aging process. By contrast, alterations in mitochondrial homeostasis ultimately producing modifications in mitochondrial biogenesis rates could play a role in the process of human senescence.
KW - Aging
KW - Mitochondrial transcription
KW - Mitochondrial translation
KW - mtDNA changes
KW - OXPHOS
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U2 - 10.1006/bmme.1997.2647
DO - 10.1006/bmme.1997.2647
M3 - Article
C2 - 9441868
AN - SCOPUS:0031430744
VL - 62
SP - 165
EP - 171
JO - Biochemical Medicine and Metabolic Biology
JF - Biochemical Medicine and Metabolic Biology
SN - 1096-7192
IS - 2
ER -