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Cited by 277Mitochondrial Function and PathologyGenetics, Aging, and Longevity in Model OrganismsAutophagy in Disease and Therapy

Influence of aging and long-term caloric restriction on oxygen radical generation and oxidative DNA damage in rat liver mitochondria

López-Torres, Mónica, Gredilla, Ricardo, Sanz, Alberto, Barja, Gustavo·2002·Free Radical Biology and Medicine
DOI 10.1016/s0891-5849(02)00773-6
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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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  • Caloric restriction decreases ROS production in rodents, particularly at Complex I, thereby preventing oxidative damage in mitochondria from heart, liver, skeletal muscle and brain.

    “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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Authors
López-Torres, M., Gredilla, R., Sanz, A., & Barja, G.
Affiliations
Universidad Complutense de Madrid (ES)
ORCID
Venue
Free Radical Biology and Medicine
Publisher
Elsevier BV
Published
2002-05
Volume
32
Issue
9
Pages
882-889
ISSN
0891-5849 (ISSN-L)
DOI
10.1016/s0891-5849(02)00773-6
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
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
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
  • Health Sciences › Medicine › Epidemiology › 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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