Journal
BIOGERONTOLOGY
Volume 10, Issue 5, Pages 579-592Publisher
SPRINGER
DOI: 10.1007/s10522-008-9200-4
Keywords
Free radical generation; Protein restriction; Aging; Protein damage; Fatty acid unsaturation; Mitochondrial respiratory complexes
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Funding
- Spanish Ministry of Education and Science [BFU2006-14495/BFI]
- Spanish Ministry of Health [RD06/0013/0012]
- Generalitat of Catalunya [2005SGR00101]
- Caixa'' Foundation
- Ministry of Education and Science [BFU2005-02584]
- CAM/UCM-GR74/07 [CCG07-UCM/BIO-2648]
- Ministry of Education and Science
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Previous studies have shown that the decrease in mitochondrial reactive oxygen species (mitROS) generation and oxidative damage to mitochondrial DNA (mtDNA) that occurs during life extending dietary restriction also occurs during protein or methionine restriction, whereas it does not take place during carbohydrate or lipid restriction. In order to study the possible effects of other amino acids, in this investigation all the dietary amino acids, except methionine, were restricted by 40% in male Wistar rats (RESTAAS group). After 6-7 weeks, experimental parameters were measured in the liver. Amino acid restriction did not change the levels of the methionine metabolites S-adenosylmethionine and S-adenosylhomocysteine, mitochondrial oxygen consumption and ROS generation, oxidative damage to mtDNA, amounts of the respiratory complexes I-IV, and the mitochondrial biogenesis factors PGC-1 alpha and NRF-2. On the other hand, adenylate energy charge, mitochondrial protein oxidation, lipooxidation and glycooxidation, the degree of mitochondrial fatty acid unsaturation, and the amount of the apoptosis inducing factor (AIF) were decreased in the RESTAAS group. Amino acid restriction also increased SIRT1 protein. These results, together with previous ones, strongly suggest that the decrease in mitROS generation and oxidative damage to mtDNA that occurs during dietary restriction is due to restriction of a single aminoacid: methionine. They also show for the first time that restriction of dietary amino acids different from methionine decreases mitochondrial protein oxidative modification and AIF, and increases SIRT1, in rat liver.
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