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

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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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Authors: López-Torres, M., Gredilla, R., Sanz, A., & Barja, G.
Affiliations: Universidad Complutense de Madrid (ES)
ORCID: Gredilla, Ricardo
Sanz, Alberto
Barja, Gustavo
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
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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Influence of aging and long-term caloric restriction on oxygen radical generation and oxidative DNA damage in rat liver mitochondria

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