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Effects of aging and methionine restriction applied at old age on ROS generation and oxidative damage in rat liver mitochondria

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Abstract

It is known that a global decrease in food ingestion (dietary restriction, DR) lowers mitochondrial ROS generation (mitROS) and oxidative stress in young immature rats. This seems to be caused by the decreased methionine ingestion of DR animals. This is interesting since isocaloric methionine restriction in the diet (MetR) also increases, like DR, rodent maximum longevity. However, it is not known if old rats maintain the capacity to lower mitROS generation and oxidative stress in response to MetR similarly to young immature animals, and whether MetR implemented at old age can reverse aging-related variations in oxidative stress. In this investigation the effects of aging and 7 weeks of MetR were investigated in liver mitochondria of Wistar rats. MetR implemented at old age decreased mitROS generation, percent free radical leak at the respiratory chain and mtDNA oxidative damage without changing oxygen consumption. Protein oxidation, lipoxidation and glycoxidation increased with age, and MetR in old rats partially or totally reversed these age-related increases. Aging increased the amount of SIRT1, and MetR decreased SIRT1 and TFAM and increased complex IV. No changes were observed in the protein amounts of PGC1, Nrf2, MnSOD, AIF, complexes I, II and III, and in the extent of genomic DNA methylation. In conclusion, treating old rats with isocaloric short-term MetR lowers mitROS production and free radical leak and oxidative damage to mtDNA, and reverses aging-related increases in protein modification. Aged rats maintain the capacity to lower mitochondrial ROS generation and oxidative stress in response to a short-term exposure to restriction of a single dietary substance: methionine.

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Abbreviations

AASA:

Aminoadipic semialdehyde

CEL:

Carboxyethyl-lysine

CML:

Carboxymethyl-lysine

DR:

Dietary restriction

FRL:

Percent free radical leak at the respiratory chain

GSA:

Glutamic semialdehyde

MetR:

Methionine restriction

mitROS:

Mitochondrial ROS

mtDNA:

Mitochondrial DNA

Nrf2:

Nuclear factor erythroid 2-related factor 2

8-oxodG:

8-Oxo-7,8-dihydro-2′deoxyguanosine

PGC1:

Peroxisome proliferator-activated receptor γ coactivator 1

ROS:

Reactive oxygen species

SIRT1:

Sirtuin 1

MnSOD:

Mitochondrial manganese superoxide dismutase

TFAM:

Mitochondrial transcription factor A

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Acknowledgments

This investigation was supported in part by I + D grants from the Spanish Ministry of Science and Innovation (BFU2008-00335/BFI) and a UCM/BSCH Grant in 2010 to G. Barja; and I + D grants from the Spanish Ministry of Science and Innovation (BFU2009-118/79BFI) and the Generalitat of Catalonia (2009SGR735) to R. Pamplona. I. Sanchez received a pre-doctoral fellowship from the Spanish Ministry of Education (FPU) and A. Gomez received a fellowship from the Spanish Ministry of Science and Innovation (FPI). We thank David Argiles for excellent technical assistance.

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Authors and Affiliations

  1. Department of Animal Physiology-II, Faculty of Biological Sciences, Complutense University of Madrid (UCM), c/Jose Antonio Novais 2, Madrid, Spain

    Inés Sanchez-Roman, Alexia Gómez, Irene Pérez, Carlota Sanchez, Henar Suarez, Mónica Lopez-Torres & Gustavo Barja

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

    Alba Naudí, Mariona Jové & Reinald Pamplona

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  1. Inés Sanchez-Roman
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  2. Alexia Gómez
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  3. Irene Pérez
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  4. Carlota Sanchez
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  6. Alba Naudí
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  9. Reinald Pamplona
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  10. Gustavo Barja
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Correspondence to Gustavo Barja.

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Sanchez-Roman, I., Gómez, A., Pérez, I. et al. Effects of aging and methionine restriction applied at old age on ROS generation and oxidative damage in rat liver mitochondria. Biogerontology 13, 399–411 (2012). https://doi.org/10.1007/s10522-012-9384-5

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