Expression of oxidative phosphorylation components in mitochondria of long-living Ames dwarf mice
Open accessAbstract
Reduced signaling of the growth hormone (GH)/insulin-like growth factor-1 (IGF-1) pathway is associated with extended life span in several species. Ames dwarf mice are GH-deficient and live >50% longer than wild-type littermates. Previously, we have shown that tissues from Ames mice exhibit elevated levels of antioxidative enzymes, less H(2)O(2) production, and lower oxidative damage suggesting that mitochondrial function may differ between genotypes. To explore the relationship between hormone deficiency and mitochondria in mice with extended longevity, we evaluated activity, protein, and gene expression of oxidative phosphorylation components in dwarf and wild-type mice at varying ages. Liver complex I + III activity was higher in dwarf mice compared to wild-type mice. The activity of I + III decreased between 3 and 20 months of age in both genotypes with greater declines in wild-type mice in liver and skeletal muscle. Complex IV activities in the kidney were elevated in 3- and 20-month-old dwarf mice relative to wild-type mice. In Ames mice, protein levels of the 39 kDa complex I subunit were elevated at 20 months of age when compared to wild-type mouse mitochondria for every tissue examined. Kidney and liver mitochondria from 20-month-old dwarf mice had elevated levels of both mitochondrially-encoded and nuclear-encoded complex IV proteins compared to wild-type mice (p < 0.05). Higher liver ANT1 and PGC-1α mRNA levels were also observed in dwarf mice. Overall, we found that several components of the oxidative phosphorylation (OXPHOS) system were elevated in Ames mice. Mitochondrial to nuclear DNA ratios were not different between genotypes despite the marked increase in PGC-1α levels in dwarf mice. The increased OXPHOS activities, along with lower ROS production in dwarf mice, predict enhanced mitochondrial function and efficiency, two factors likely contributing to long-life in Ames mice.
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The improved mitochondrial bioenergetics in Ames dwarf and GHR-KO mice is accompanied by increased expression of PGC1α and OXPHOS proteins.
“accompanied by increased expression of peroxisome proliferator-activated receptor-γ coactivator 1α (PGC1α) as well as proteins involved in OXPHOS26.”
From Mitochondrial and metabolic dysfunction in ageing and age-related diseases (2022) · cites this paper as [26]
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Mitochondrial and metabolic dysfunction in ageing and age-related diseases
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- Authors
- Brown-Borg, H. M., Johnson, W. T., & Rakoczy, S. G.
- Affiliations
- Agricultural Research Service (US)
- University of North Dakota (US)
- ORCID
- Johnson, W. Thomas
- Venue
- AGE
- Published
- 2011-02-16
- Volume
- 34
- Issue
- 1
- Pages
- 43-57
- ISSN
- 0161-9152 (ISSN-L)
- 1574-4647
- PMC
- PMC3260352
- OpenAlex
- W2038054416
- Cited by
- 52
- References
- 60
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 5 · 2022: 3 · 2021: 4 · 2020: 5 · 2019: 6 · 2018: 4 · 2017: 2 · 2016: 3 · 2015: 4 · 2014: 2 · 2013: 2 · 2012: 6
- FWCI
- 1.40
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- AGE (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- U.S. Public Health Service (01322899)
- National Institute on Aging (R15AG022909, R01AG034206)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Keywords
- Ames dwarf mice, oxidative phosphorylation, mitochondrial function, longevity, growth hormone deficiency, IGF-1 signaling, complex I, cytochrome c oxidase, ANT1, PGC-1α, reactive oxygen species, mitochondrial DNA, liver mitochondria, skeletal muscle mitochondria, kidney mitochondria
- MeSH terms
- Animals, Disease Models, Animal, Dwarfism, Pituitary, Hydrogen Peroxide, Insulin-Like Growth Factor I, Liver, Longevity, Mice, Mutant Strains, Mitochondria, Oxidation-Reduction, Oxidative Phosphorylation, Growth Hormone, Signal Transduction, Mice
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