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Influence of aging and long-term caloric restriction on oxygen radical generation and oxidative DNA damage in rat liver mitochondria
Abstract
The effect of long-term caloric restriction and aging on the rates of mitochondrial H2O2 production and oxygen consumption as well as on oxidative damage to nuclear (nDNA) and mitochondrial DNA (mtDNA) was studied in rat liver tissue. Long-term caloric restriction significantly decreased H2O2 production of rat liver mitochondria (47% reduction) and significantly reduced oxidative damage to mtDNA (46% reduction) with no changes in nDNA. The decrease in ROS production was located at complex I because it only took place with complex I-linked substrates (pyruvate/malate) but not with complex II-linked substrates (succinate). The mechanism responsible for that decrease in ROS production was not a decrease in mitochondrial oxygen consumption because it did not change after long-term restriction. Instead, the caloric restricted mitochondria released less ROS per unit electron flow, due to a decrease in the reduction degree of the complex I generator. On the other hand, increased ROS production with aging in state 3 was observed in succinate-supplemented mitochondria because old control animals were unable to suppress H2O2 production during the energy transition from state 4 to state 3. The levels of 8-oxodG in mtDNA increased with age in old animals and this increase was abolished by caloric restriction. These results support the idea that caloric restriction reduces the aging rate at least in part by decreasing the rate of mitochondrial ROS production and so, the rate of oxidative attack to biological macromolecules like mtDNA.
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“Originally, it was shown that CR decreases ROS production in rodents, particularly at Complex I, thereby preventing oxidative damage in mitochondria from heart (Gredilla et al., 2002), liver (Lopez-Torres et al., 2002), skeletal muscle (Lass et al., 1998) and brain (Sanz et al., 2005).”
From Role of the mitochondrial DNA replication machinery in mitochondrial DNA mutagenesis, aging and age-related diseases (2017) · cites this paper as Lopez-Torres et al., 2002
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Metadata
- Authors
- López-Torres, M., Gredilla, R., Sanz, A., & Barja, G.
- Affiliations
- Universidad Complutense de Madrid (ES)
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2002-05
- Volume
- 32
- Issue
- 9
- Pages
- 882-889
- ISSN
- 0891-5849 (ISSN-L)
- OpenAlex
- W2089814579
- Cited by
- 277
- References
- 55
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 1 · 2023: 3 · 2022: 4 · 2021: 5 · 2020: 2 · 2019: 6 · 2018: 5 · 2017: 7 · 2016: 3 · 2015: 9 · 2014: 16 · 2013: 12 · 2012: 7
- FWCI
- 8.44
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Free Radical Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion)
- Funders
- National Research Foundation
- 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 › Cell Biology › Autophagy in Disease and Therapy
- Keywords
- caloric restriction, aging, liver mitochondria, reactive oxygen species, hydrogen peroxide production, oxidative DNA damage, mitochondrial DNA, nuclear DNA, complex I, 8-oxoguanine, mitochondrial oxygen consumption, succinic acid, pyruvate-malate
- MeSH terms
- 8-Hydroxy-2'-Deoxyguanosine, Aging, Animals, Cell Nucleus, Deoxyguanosine, Diet, Reducing, DNA, DNA Damage, DNA, Mitochondrial, Hydrogen Peroxide, Malates, Male, Mitochondria, Liver, Oxidation-Reduction, Oxygen, Rats, Wistar, Reactive Oxygen Species, Oxidative Stress, Pyruvic Acid, Succinic Acid, Rats
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