Caloric restriction decreases mitochondrial free radical generation at complex I and lowers oxidative damage to mitochondrial DNA in the rat heart
Abstract
The effect of caloric restriction (CR) (40%) on the rates of mitochondrial H 2 O 2 production and oxygen consumption and oxidative damage to nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) was studied for short‐term (6‐wk) and long‐term (1‐year) periods in the heart of young and old rats. Short‐term CR did not change any of the parameters measured. However, long‐term CR significantly decreased the rate of mitochondrial H 2 O 2 generation (by 45%) and significantly lowered oxidative damage to mtDNA (by 30%) without modifying damage to nDNA. The decrease in H 2 O 2 production occurred exclusively at the complex I free radical generator of the respiratory chain. The mechanism allowing that decrease was not a simple decrease in mitochondrial oxygen consumption. Instead, the mitochondria of caloric‐restricted animals released fewer oxygen radicals per unit electron flow in the respiratory chain. This was due to a decrease in the degree of reduction of the complex I generator in caloric‐restricted mitochondria. The results are consistent with the concept that CR decreases the aging rate at least in part by decreasing the rate of mitochondrial oxygen radical generation and then the rate of attack on mtDNA.
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Resveratrol increases mitochondrial biogenesis partly through activation of SIRT1 and PGC-1α.
“However, resveratrol, a naturally occurring small molecule that induces metabolic benefits resembling those of CR, does increase mitochondrial biogenesis, in part through activation of SIRT1 and PGC-1α116.”
From Stem cell aging: mechanisms, regulators and therapeutic opportunities (2014) · cites this paper as [116]
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- Authors
- Gredilla, R., Sanz, A., Lopez-Torres, M., & Barja, G.
- Affiliations
- Universidad Complutense de Madrid (ES)
- Department of Animal Biology‐II (Animal Physiology) Faculty of Biology Complutense University Madrid 28040 Spain
- Venue
- The FASEB Journal
- Publisher
- Wiley
- Published
- 2001-05-09
- Volume
- 15
- Issue
- 9
- Pages
- 1589-1591
- ISSN
- 0892-6638 (ISSN-L)
- 1530-6860
- OpenAlex
- W2143996615
- Cited by
- 372
- References
- 45
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 7 · 2023: 8 · 2022: 6 · 2021: 13 · 2020: 4 · 2019: 8 · 2018: 9 · 2017: 8 · 2016: 15 · 2015: 7 · 2014: 17 · 2013: 19 · 2012: 19
- FWCI
- 6.30
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The FASEB Journal (publishedVersion)
- PubMed (publishedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion)
- Funders
- National Science Foundation, United Arab Emirates (99/1049)
- 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, mitochondrial free radicals, complex I, mitochondrial DNA oxidation, hydrogen peroxide production, oxidative DNA damage, heart, aging, electron transport chain, oxygen consumption
- MeSH terms
- Animals, Calorimetry, DNA, Mitochondrial, Free Radicals, Heart, Hydrogen Peroxide, Mitochondria, Myocardium, Rats, Wistar, Oxidative Stress, Rats
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