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?

Every Other Day Feeding Schedule Mimics Dietary Restriction without Lowered IGF-1

http://www.ncbi.nlm.nih.gov/pubmed/18593280?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_Discovery_RA&linkpos=5&log$=relatedarticles&logdbfrom=pubmed


1: Rejuvenation Res. 2008 Jun;11(3):621-9.Click here to read Links
Effect of every other day feeding on mitochondrial free radical production and oxidative stress in mouse liver.
Caro P, Gómez J, López-Torres M, Sánchez I, Naudi A, Portero-Otín M, Pamplona R, Barja G.

Department of Animal Physiology-II, Complutense University, Madrid, Spain.

It is known that dietary restriction (DR) increases maximum longevity in rodents, but the mechanisms involved remain unknown. Among the possible mechanisms, several lines of evidence support the idea that decreases in mitochondrial oxidative stress and in insulin signaling are involved but it is not known if they are interconnected. It has been reported that when C57BL/6 mice are maintained on an every other day (EOD) feeding their overall food intake is only slightly decreased and plasma insulin-like growth factor (IGF)-1 is even somewhat increased. In spite of this, their maximum longevity is increased, analogously to what occurs in classic DR. Thus, this model dissociates the increase in longevity from the decrease in IGF-1 observed in classic DR. Based on these facts, we have studied the effect of EOD DR on the rate of mitochondrial reactive oxygen species (ROS) production, oxygen consumption, and the percent free radical leak (FRL) of well-coupled liver mitochondria, the marker of mtDNA oxidative damage 8-oxo-7,8-dihydro-2'deoxyguanosine (8-oxodG), the content of complexes I to IV of the respiratory chain, the apoptosis inducing factor (AIF), PGC1-alpha, UCP2, five different markers of oxidative damage to proteins and the full fatty acid composition on C57BL/6 mice liver. It was found that EOD DR decreased ROS production in complex I but not in complex III without changes in oxygen consumption. As a result, FRL was decreased in complex I. Oxidative damage to mtDNA (8-oxodG) and protein oxidation, glycoxidation and lipoxidation were also lower in the EOD restricted group in comparison with the control one while the degree of fatty acid unsaturation was held constant. The EOD group also showed decreases in AIF, PGC1-alpha, and UCP2. These results support the possibility that EOD DR increases maximum life span at least in part through decreases in mitochondrial oxidative stress which are independent from insulin/IGF-1-like signaling.

PMID: 18593280 [PubMed - indexed for MEDLINE]

Methionine Restriction Reduces MitROS

http://www.fasebj.org/cgi/content/abstract/20/8/1064

© 2006 FASEB
Methionine restriction decreases mitochondrial oxygen radical generation and leak as well as oxidative damage to mitochondrial DNA and proteins
Alberto Sanz*, Pilar Caro*, Victoria Ayala{dagger}, Manuel Portero-Otin{dagger}, Reinald Pamplona{dagger} and Gustavo Barja*,1

* Department of Animal Physiology-II, Complutense University, Madrid, Spain;

{dagger} Department of Basic Medical Sciences, University of Lleida, Lleida, Spain

1Correspondence: Departamento de Fisiología Animal-II, Facultad de Ciencias Biológicas, Universidad Complutense, c/Antonio Novais-2, Madrid 28040, Spain. E-mail: gbarja@bio.ucm.es

Previous studies have consistently shown that caloric restriction (CR) decreases mitochondrial reactive oxygen species (ROS) (mitROS) generation and oxidative damage to mtDNA and mitochondrial proteins, and increases maximum longevity, although the mechanisms responsible for this are unknown. We recently found that protein restriction (PR) also produces these changes independent of energy restriction. Various facts link methionine to aging, and methionine restriction (MetR) without energy restriction increases, like CR, maximum longevity. We have thus hypothesized that MetR is responsible for the decrease in mitROS generation and oxidative stress in PR and CR. In this investigation we subjected male rats to exactly the same dietary protocol of MetR that is known to increase their longevity. We have found, for the first time, that MetR profoundly decreases mitROS production, decreases oxidative damage to mtDNA, lowers membrane unsaturation, and decreases all five markers of protein oxidation measured in rat heart and liver mitochondria. The concentration of complexes I and IV also decreases in MetR. The decrease in mitROS generation occurs in complexes I and III in liver and in complex I in heart mitochondria, and is due to an increase in efficiency of the respiratory chain in avoiding electron leak to oxygen. These changes are strikingly similar to those observed in CR and PR, suggesting that the decrease in methionine ingestion is responsible for the decrease in mitochondrial ROS production and oxidative stress, and possibly part of the decrease in aging rate, occurring during caloric restriction.—Sanz, A., Caro, P., Ayala, V., Portero-Otin, M., Pamplona, R., Barja, G. Methionine restriction decreases mitochondrial oxygen radical generation and leak as well as oxidative damage to mitochondrial DNA and proteins.


Key Words: mitochondria • methionine restriction • caloric restriction • free radicals • aging • DNA damage • oxidative damage