TY - JOUR
T1 - Effects of aging on mitochondrial DNA copy number and cytochrome c oxidase gene expression in rat skeletal muscle, liver, and heart
AU - Barazzoni, Rocco
AU - Short, Kevin R.
AU - Nair, K. Sreekumaran
PY - 2000/2/4
Y1 - 2000/2/4
N2 - Mitochondrial DNA (mtDNA) deletions and mutations have been reported to occur with aging in various tissues. To determine the functional impact of these changes, we measured mtDNA copy number, mitochondria-encoded cytochrome c oxidase (COX) subunit I and III transcript levels, and COX enzyme activity in skeletal muscles (medial and lateral gastrocnemius and soleus), liver, and heart in 6- and 27-month-old rats. Substantial age-related reductions of mtDNA copy number occurred in skeletal muscle groups (-23-40%, p < 0.03) and liver (-50%, p < 0.01) but not in the heart. The decline in mtDNA was not associated with reduced COX transcript levels in tissues with high oxidative capacities such as red soleus muscle or liver, while transcript levels were reduced with aging in the less oxidative mixed fiber gastrocnemius muscle (- 17-22%, p < 0.05). Consistent with transcript levels, COX activity also remained unchanged in aging liver and heart but declined with age in the lateral gastrocnemius (-32%, p < 0.05). Thus, the effects of aging on mitochondrial gene expression are tissue-specific. A substantial age-related decline in mtDNA copy number proportional to tissue oxidative capacities is demonstrated in skeletal muscle and liver. mtDNA levels are in contrast preserved in the aging heart muscle, presumably due to its incessant aerobic activity. Reduced mtDNA copy number has no major effects on mitochondrial encoded transcript levels and enzyme activities in various tissues under these baseline study conditions. In contrast, maintenance of mitochondrial transcript levels that may be linked to oxidative metabolism and energy demand appears to be the main determinant of mitochondrial oxidative capacity in aging tissues.
AB - Mitochondrial DNA (mtDNA) deletions and mutations have been reported to occur with aging in various tissues. To determine the functional impact of these changes, we measured mtDNA copy number, mitochondria-encoded cytochrome c oxidase (COX) subunit I and III transcript levels, and COX enzyme activity in skeletal muscles (medial and lateral gastrocnemius and soleus), liver, and heart in 6- and 27-month-old rats. Substantial age-related reductions of mtDNA copy number occurred in skeletal muscle groups (-23-40%, p < 0.03) and liver (-50%, p < 0.01) but not in the heart. The decline in mtDNA was not associated with reduced COX transcript levels in tissues with high oxidative capacities such as red soleus muscle or liver, while transcript levels were reduced with aging in the less oxidative mixed fiber gastrocnemius muscle (- 17-22%, p < 0.05). Consistent with transcript levels, COX activity also remained unchanged in aging liver and heart but declined with age in the lateral gastrocnemius (-32%, p < 0.05). Thus, the effects of aging on mitochondrial gene expression are tissue-specific. A substantial age-related decline in mtDNA copy number proportional to tissue oxidative capacities is demonstrated in skeletal muscle and liver. mtDNA levels are in contrast preserved in the aging heart muscle, presumably due to its incessant aerobic activity. Reduced mtDNA copy number has no major effects on mitochondrial encoded transcript levels and enzyme activities in various tissues under these baseline study conditions. In contrast, maintenance of mitochondrial transcript levels that may be linked to oxidative metabolism and energy demand appears to be the main determinant of mitochondrial oxidative capacity in aging tissues.
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U2 - 10.1074/jbc.275.5.3343
DO - 10.1074/jbc.275.5.3343
M3 - Article
C2 - 10652323
AN - SCOPUS:0034602958
SN - 0021-9258
VL - 275
SP - 3343
EP - 3347
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 5
ER -