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Forty percent and eighty percent methionine restriction decrease mitochondrial ROS generation and oxidative stress in
Pilar Caro1, José Gómez, Mónica López-Torres
1Departamento de Fisiología Animal-II, Facultad de Ciencias Biológicas, Complutense University, c/Jose Antonio Novais-2, Madrid 28040, Spain.
Abstract:
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.
Insights
Dietary methionine restriction (MetR) in rats significantly reduces mitochondrial reactive oxygen species (ROS) and oxidative stress. Even a 40% MetR is sufficient to achieve these beneficial effects, suggesting methionine intake is key to dietary restriction benefits.
Area of Science:
- Gerontology
- Mitochondrial Biology
- Nutritional Science
Background:
- Dietary restriction (DR) extends lifespan and reduces oxidative stress in rodents.
- Protein restriction (PR) and methionine restriction (MetR) mimic some DR effects.
- Previous MetR studies used 80% restriction and methionine substitution.
Purpose of the Study:
- To determine if methionine restriction (MetR) alone can reduce ROS production and oxidative stress.
- To investigate the effects of 40% and 80% MetR on Wistar rats.
- To clarify MetR's role in mediating DR-induced oxidative stress reduction.
Main Methods:
- Wistar rats were subjected to 40% or 80% isocaloric methionine restriction.
- Mitochondrial ROS generation and free radical leak were measured in liver mitochondria.
- Levels of mitochondrial DNA oxidative damage and various protein oxidation markers were assessed.
Main Results:
- Both 40% and 80% MetR significantly decreased mitochondrial ROS generation and free radical leak.
- MetR lowered oxidative damage to mitochondrial DNA and multiple markers of protein oxidation.
- Key mitochondrial components like complexes I and III were also affected by MetR.
Conclusions:
- 40% isocaloric methionine restriction is sufficient to decrease ROS production and oxidative stress in rat liver.
- Reduced methionine intake appears to be the primary driver of oxidative stress reduction seen in dietary restriction.
- These findings highlight the critical role of methionine in metabolic health and aging.
