Effect of 40% restriction of dietary amino acids (except methionine) on mitochondrial oxidative stress and biogenesis, AIF and SIRT1 in rat liver

Abstract

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-1alpha 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.

The Mitochondrial Free Radical Theory of Aging

“…83 In addition, we have recently found that 40% MetR also decreases mtROSp, %FRL, and 8-oxodG in mtDNA and reverses aging-related increases in protein modification when implemented at old age (during 7 weeks in 24-month-old rats). 82 All those results, taken together, indicate that the lowered ingestion of methionine during MetR (and PR and DR) is responsible for the decreases in mitochondrial ROSp and oxidative stress observed in MetR (and PR and DR), and possibly for all (during PR and MetR) or part (during DR) of the life-extension effect observed during these dietary manipulations.…”

Resveratrol reduces lipid peroxidation and increases sirtuin 1 expression in adult animals programed by neonatal protein restriction

“…Studies have shown that methionine restriction can decrease mitochondrial ROS production and oxidative stress (Caro et al 2009a). Restriction of dietary amino acids other than methionine decreases mitochondrial protein oxidation and increases SIRT1 in rat liver (Caro et al 2009b).…”

Dietary restriction of amino acids other than methionine prevents oxidative damage during aging: Involvement of telomerase activity and telomere length

“…While feeding with PREMD significantly decreased protein carbonyl levels both in the liver homogenate and mitochondria of aging rats, it significantly prevented 8-OHdG formation only in mtDNA. There is limited number of studies evaluating the effects of PREMD on aging (Caro et al, 2009a(Caro et al, , 2009b. In these studies, 7 weeks old Wistar rats fed with PREMD for seven weeks did not exhibit any beneficial effects neither on superoxide and peroxide production rates nor 8-OHdG formation in the liver mitochondria.…”