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Effects of Aging on Mitochondrial DNA Copy Number and Cytochromec Oxidase Gene Expression in Rat Skeletal Muscle, Liver, and Heart
Open accessAbstract
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 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.
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“Age-associated alterations have been reported in skeletal muscle at both transcriptional and functional levels of mitochondrial gene expression (27).”
From Discovering pathways of sarcopenia in older adults: a role for insulin resistance on mitochondria dysfunction (2011) · cites this paper as [27]
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“Multiple groups have reported a decrease in skeletal muscle mitochondrial content and function with age.126-128”
From Hormonal and Metabolic Changes of Aging and the Influence of Lifestyle Modifications (2021) · cites this paper as [127]
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Metadata
- Authors
- Barazzoni, R., Short, K. R., & Nair, K. S.
- Affiliations
- Mayo Clinic (US)
- Corresponding author
- Nair, K.Sreekumaran
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2000-02
- Volume
- 275
- Issue
- 5
- Pages
- 3343-3347
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2011919513
- Cited by
- 367
- References
- 37
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 7 · 2023: 8 · 2022: 18 · 2021: 18 · 2020: 13 · 2019: 15 · 2018: 11 · 2017: 12 · 2016: 12 · 2015: 11 · 2014: 17 · 2013: 17 · 2012: 20
- FWCI
- 4.70
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- ArTS Archivio della ricerca di Trieste (University of Trieste https://www.units.it/) (submittedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (R0 AG 09531, R01AG009531)
- National Center for Research Resources (RR-00585, M01RR000585)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Keywords
- aging, mitochondrial DNA copy number, cytochrome c oxidase, mitochondrial gene expression, skeletal muscle, liver, heart, oxidative capacity, tissue-specific aging, gastrocnemius, soleus muscle
- MeSH terms
- Aging, Animals, Electron Transport Complex IV, DNA, Mitochondrial, Heart, Liver, Male, Rats, Inbred F344, Gene Expression, Muscle, Skeletal, Rats
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