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J Biol Chem, Vol. 275, Issue 5, 3343-3347, February 4, 2000
From the Endocrine Research Unit, Mayo Clinic and Foundation,
Rochester, Minnesota 55905
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 (
Effects of Aging on Mitochondrial DNA Copy Number and Cytochrome
c Oxidase Gene Expression in Rat Skeletal Muscle, Liver,
and Heart*
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 base-line 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.
*
This work was supported by National Institutes of Health
Grants RO AG 09531 and RR 00585.The costs of publication of this article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Mayo Clinic, Endocrine
Research Unit, Joseph 5-194, Rochester, MN 55905. Tel.: 507-255-2949;
Fax: 507-255-4828; E-mail: nair.sree@mayo.edu.
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