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Forty percent and eighty percent methionine restriction decrease mitochondrial ROS generation and oxidative stress in rat liver

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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.

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Abbreviations

AIF:

Apoptosis inducing factor

AASA:

Aminoadipic semialdehyde in proteins

CEL:

Carboxyethyl-lysine in proteins

CML:

Carboxymethyl-lysine in proteins

DBI:

Double bond index

DR:

Dietary restriction

PI:

Peroxidizability index

PR:

Protein restriction

GSA:

Glutamic semialdehyde in proteins

MDAL:

Malondialdehyde-lysine in proteins

MetR:

Methionine restriction

ROS:

Reactive oxygen species

8-oxodG:

8-Oxo-7,8-dihydro-2′deoxyguanosine

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Acknowledgments

This study was supported in part by I + D grants from the Spanish Ministry of Education and Science (BFU2006-14495/BFI), the Spanish Ministry of Health (ISCIII, Red de Envejecimiento y Fragilidad, RD06/0013/0012), the Generalitat of Catalunya (2005SGR00101) and “La Caixa” Foundation to R. Pamplona; and from the Ministry of Education and Science (BFU2005-02584) and from CAM/UCM groups (910521) to G. Barja; A. Naudi received a predoctoral fellowship from “La Caixa” Foundation. P. Caro and J. Gómez received predoctoral fellowships from the Ministry of Education and Science. We thank David Argiles for excellent technical assistance.

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Authors and Affiliations

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

    Pilar Caro, José Gómez, Mónica López-Torres, Inés Sánchez & Gustavo Barja

  2. Department of Experimental Medicine, University of Lleida-IRBLLEIDA, Lleida, 25008, Spain

    Alba Naudí, Mariona Jove & Reinald Pamplona

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  1. Pilar Caro
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  2. José Gómez
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  3. Mónica López-Torres
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  4. Inés Sánchez
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  5. Alba Naudí
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  6. Mariona Jove
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  7. Reinald Pamplona
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  8. Gustavo Barja
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Correspondence to Gustavo Barja.

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Caro, P., Gómez, J., López-Torres, M. et al. Forty percent and eighty percent methionine restriction decrease mitochondrial ROS generation and oxidative stress in rat liver. Biogerontology 9, 183–196 (2008). https://doi.org/10.1007/s10522-008-9130-1

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