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Effect of 8.5% and 25% caloric restriction on mitochondrial free radical production and oxidative stress in rat liver

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Abstract

Previous studies have consistently shown that 40% caloric restriction (CR) decreases the rate of mitochondrial ROS production and steady-state levels of markers of oxidative damage to macromolecules including mitochondrial DNA. However, few investigations have studied whether these changes also occur in lower CR regimes. This is of potential interest since moderate levels of dietary restriction are more practicable for humans. In this investigation male Wistar rats were subjected to 8.5% and 25% caloric restriction. Neither 8.5% nor 25% CR changed mitochondrial ROS production, oxygen consumption or mtDNA oxidative damage in rat liver mitochondria. However, both 8.5% and 25% CR significantly decreased the five different markers of protein oxidation, glycoxidation and lipoxidation measured, aminoadipic and glutamic semialdehyde, carboxyethyl-lysine, carboxymethyl-lysine, and malondialdehyde-lysine. The fatty acid composition of liver mitochondria was also affected and led to a moderate decrease in the degree of membrane unsaturation in both 8.5% and 25% CR. While 8.5% CR only affected complex I concentration (which was decreased), 25% CR decreased complexes I and IV and increased complexes II and III of the respiratory chain. Apoptosis-inducing factor (AIF) significantly decreased in 25% CR but not in 8.5% CR. The results show that moderate levels of caloric restriction can have beneficial effects including decreases in oxidative protein modification and a lower sensitivity of membranes to lipid peroxidation, in association with a reprogramming of the respiratory chain complexes and AIF content.

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Abbreviations

AASA:

Aminoadipic semialdehyde in proteins

CEL:

Carboxyethyl-lysine in proteins

CML:

Carboxymethyl-lysine in proteins

DBI:

Double bond index

GSA:

Glutamic semialdehyde in proteins

MDAL:

Malondialdehyde-lysine in proteins

MtDNA:

Mitochondrial DNA

8-oxodG:

8-oxo-7,8-dihydro-2′-deoxyguanosine

ROS:

Reactive oxygen species

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Acknowledgements

This study was supported in part by I + D grants from the Spanish Ministry of Education and Science (BFU2006-14495/BFI), Spanish Ministry of Health (ISCIII, Red de Envejecimiento y Fragilidad, RD06/0013/0012), and the Generalitat of Catalunya (2005SGR00101) to R.P.; from the COST B35 Action, Spanish Ministry of Health (FIS 05-2241), Spanish Ministry of Education and Science (AGL2006-12433), and “La Caixa” Foundation to M.P.O.; and from the Spanish Ministry of Education and Science (BFU2005-02584) and from CAM/UCM groups (910521) to G.B.; 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. Department of Animal Physiology-II, Complutense University, c/Antonio Novais-2, Madrid, 28040, Spain

    José Gómez, Pilar Caro & Gustavo Barja

  2. Department of Basic Medical Sciences, University of Lleida, Lleida, 25008, Spain

    Alba Naudí, Manuel Portero-Otin & Reinald Pamplona

Authors
  1. José Gómez
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  2. Pilar Caro
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  3. Alba Naudí
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  4. Manuel Portero-Otin
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  5. Reinald Pamplona
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  6. Gustavo Barja
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Correspondence to Gustavo Barja.

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Gómez, J., Caro, P., Naudí, A. et al. Effect of 8.5% and 25% caloric restriction on mitochondrial free radical production and oxidative stress in rat liver. Biogerontology 8, 555–566 (2007). https://doi.org/10.1007/s10522-007-9099-1

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  • DOI: https://doi.org/10.1007/s10522-007-9099-1

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