40% and 80% Methionine Restriction Reduce MitROS

Forty percent and eighty percent methionine restriction decrease mitochondrial ROS generation and oxidative stress in rat liver.
Caro P, Gómez J, López-Torres M, Sánchez I, Naudí A, Jove M, Pamplona R, Barja G.

Departamento de Fisiología Animal-II, Facultad de Ciencias Biológicas, Complutense University, c/Jose Antonio Novais-2, Madrid 28040, Spain.

Dietary restriction (DR) lowers mitochondrial reactive oxygen species (ROS) generation and oxidative damage and increases maximum longevity in rodents. Protein restriction (PR) or methionine restriction (MetR), but not lipid or carbohydrate restriction, also cause those kinds of changes. However, previous experiments of MetR were performed only at 80% MetR, and substituting dietary methionine with glutamate in the diet. In order to clarify if MetR can be responsible for the lowered ROS production and oxidative stress induced by standard (40%) DR, Wistar rats were subjected to 40% or 80% MetR without changing other dietary components. It was found that both 40% and 80% MetR decrease mitochondrial ROS generation and percent free radical leak in rat liver mitochondria, similarly to what has been previously observed in 40% PR and 40% DR. The concentration of complexes I and III, apoptosis inducing factor, oxidative damage to mitochondrial DNA, five different markers of protein oxidation, glycoxidation or lipoxidation and fatty acid unsaturation were also lowered. The results show that 40% isocaloric MetR is enough to decrease ROS production and oxidative stress in rat liver. This suggests that the lowered intake of methionine is responsible for the decrease in oxidative stress observed in DR.

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The abstract really should have specified the measurable oxidation differences in 40% vs. 80% methionine restriction. Are the effects additive, or is there a minimum threshold for positive results, beyond which no further benefits are derived?