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Caloric restriction decreases mitochondrial free radical generation at complex I and lowers oxidative damage to mitochondrial DNA in the rat heart
Author(s) -
Gredilla Ricardo,
Sanz Alberto,
Lopez-Torres Monica,
Barja Gustavo
Publication year - 2001
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.00-0764fje
Subject(s) - mitochondrial dna , caloric theory , oxidative damage , oxidative phosphorylation , mitochondrion , chemistry , oxidative stress , dna , biophysics , biology , biochemistry , endocrinology , gene
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.