Mitochondrial dysfunction in the senescence accelerated mouse (SAM).
Oxidative damage to DNA, proteins, and lipids in mitochondria caused by free radicals may be one factor in aging. Oxidative phosphorylation was estimated in liver mitochondria from senescence accelerated mice (SAMP8) and a senescence resistant substrain (SAMR1). The respiratory control ratio decreased in liver mitochondria of SAMP8 during aging, and it was estimated that at 18 months of age this respiratory control value suggested that it might be insufficient to provide ATP synthesis necessary for normal cell metabolism. In addition, the ADP/O, an index of efficiency of ATP synthesis, was depressed at 18 months of age. Dinitrophenol-dependent uncoupled respiration in liver mitochondria of SAMP8 mice was markedly decreased with aging, suggesting a dysfunctional energy transfer mechanism in mitochondria of aged SAMP8 mice. Active uptake of calcium in liver mitochondria was markedly dysfunctional in SAMP8 mice with aging, and uncoupling of respiration was induced more easily in aged mitochondria. Milder effects on these functional parameters were observed in SAMR1 mice. A similar dysfunction was also observed in heart mitochondria of SAMP8 mice at 12 months of age. The amount of Bcl-x in liver mitochondria was slightly decreased in SAMP8. We suggest that these changes in mitochondrial function may be related to the shorter life span of the senescence accelerated mouse.
Nakahara
H
H
Institute of Medical Science, Center for Adult Diseases, Kuraashiki, Japan.
Kanno
T
T
Inai
Y
Y
Utsumi
K
K
Hiramatsu
M
M
Mori
A
A
Packer
L
L
D000375:Aging / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000502:physiology; D019069:Cell Respiration / Q000502:physiology; D005609:Free Radicals; D006861:Hydrogen Peroxide / Q000378:metabolism; D015227:Lipid Peroxidation / Q000502:physiology; D051379:Mice; D008813:Mice, Inbred ICR; D008929:Mitochondria, Heart / Q000502:physiology*; D008930:Mitochondria, Liver / Q000502:physiology*; D010085:Oxidative Phosphorylation; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
D005609:Free Radicals; D011518:Proto-Oncogene Proteins; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase; D002118:Calcium