Age-related changes in brain mitochondrial DNA deletion and oxidative stress are differentially modulated by dietary fat type and coenzyme Q10

doi:10.1016/j.freeradbiomed.2011.02.004

Free Radical Biology and Medicine

Volume 50, Issue 9, 1 May 2011, Pages 1053-1064

https://doi.org/10.1016/j.freeradbiomed.2011.02.004 Get rights and content

Abstract

Mitochondria-related oxidative damage is a primary event in aging and age-related neurodegenerative disorders. Some dietary treatments, such as antioxidant supplementation or the enrichment of mitochondrial membranes with less oxidizable fatty acids, reduce lipid peroxidation and lengthen life span in rodents. This study compares life-long feeding on monounsaturated fatty acids (MUFAs), such as virgin olive oil, and n-6 polyunsaturated fatty acids, such as sunflower oil, with or without coenzyme Q₁₀ supplementation, with respect to age-related molecular changes in rat brain mitochondria. The MUFA diet led to diminished age-related phenotypic changes, with lipoxidation-derived protein markers being higher among the older animals, whereas protein carbonyl compounds were lower. It is noteworthy that the MUFA diet prevented the age-related increase in levels of mitochondrial DNA deletions in the brain mitochondria from aged animals. The findings of this study suggest that age-related oxidative stress is related, at the mitochondrial level, to other age-related features such as mitochondrial electron transport and mtDNA alterations, and it can be modulated by selecting an appropriate dietary fat type and/or by suitable supplementation with low levels of the antioxidant/electron carrier molecule coenzyme Q.

Section snippets

Chemicals

All the chemical products and solvents, of the highest grade available, were acquired from Sigma (St. Louis, MO, USA) and Merck (Darmstadt, Germany).

Animals and diets

A total of 64 male Wistar rats (Rattus norvegicus) initially weighing 80–90 g were housed four to a cage and maintained in a 12-h light/12-h dark cycle, with free access to food and water. The rats were randomly assigned to four experimental groups and fed from weaning until 24 months of age a semisynthetic and isoenergetic diet according to the

Body weight, brain weight, and food intake

The body weights of the animals were similar for all groups at 6 and at 24 months (data not shown). Aging led to similar increases in body weight for all groups. No differences concerning brain weight were found between groups or by age (data not shown). The brain-to-body weight ratios (data not shown) were similar for all groups, being lower at 24 months. No differences concerning food intake were found between groups or in relation to age.

Mitochondrial fatty-acid profile

When a nutritional intervention is conducted, the

Discussion

Studies of dietary fat (mainly long-chain PUFAs from the (n-3) family) effects on neurobiology and neurodegeneration have a long history [43]. There are important links between fatty acid unsaturation and aging: it has been previously reported that n-6 PUFA-rich diets lead to higher levels of lipid peroxidation and DNA double-strand breaks in rat tissues and blood during aging, compared with MUFA-based diets [9], [10], [11], [12]. Moreover, it has been described that long-lived animals have

Acknowledgments

This study was supported in part by I + D grants from the Spanish Ministry of Education and Science (1FD97-0457-c02-01, BFU2009-11879/BFI, AGL2006-12433, and AGL2008-01057), the Spanish Ministry of Health (Red de Envejecimiento y Fragilidad RD06/0013/0012, PI04/0355, and PI05/2214), and the Autonomous Government of Andalusia (AGR832) and Catalonia (2009SGR735). We thank David Argiles for excellent technical assistance. We are also grateful to Dr. Ricardo Ramos, from the Genomic Facility of the

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Original ContributionAge-related changes in brain mitochondrial DNA deletion and oxidative stress are differentially modulated by dietary fat type and coenzyme Q10

Abstract

Section snippets

Chemicals

Animals and diets

Body weight, brain weight, and food intake

Mitochondrial fatty-acid profile

Discussion

Acknowledgments

Mech. Ageing Dev.

Free Radic. Biol. Med.

Exp. Gerontol.

Mech. Ageing Dev.

Exp. Gerontol.

Methods Enzymol.

J. Biol. Chem.

J. Lipid Res.

J. Ethnopharmacol.

Biochim. Biophys. Acta

Biochem. Biophys. Res. Commun.

Methods Enzymol.

Anal. Biochem.

J. Biol. Chem.

Mutat. Res.

Methods

J. Lipid Res.

J. Lipid Res.

Am. J. Clin. Nutr.

Prostaglandins Leukot. Essent. Fatty Acids

Int. J. Biochem. Cell Biol.

Mitochondrion

Clin. Chim. Acta

Free Radic. Biol. Med.

Biochem. Biophys. Res. Commun.

Free Radic. Biol. Med.

Free Radic. Biol. Med.

Biochim. Biophys. Acta

Mech. Ageing Dev.

Free Radic. Biol. Med.

Exp. Gerontol.

Free Radic. Biol. Med.

J. Biol. Chem.

Aging: a theory based on free radical and radiation chemistry

J. Gerontol.

Brain mitochondrial dysfunction in ovariectomized mice injected with d-galactose

Neurochem. Res.

Mitochondrial oxygen consumption and reactive oxygen species production are independently modulated: implications for aging studies

Rejuvenation Res.

Mitochondrial role in cell aging

Exp. Gerontol.

Mitochondrial threshold effects

Biochem. J.

Oxidative damage to mitochondria and aging

Exp. Gerontol.

Age-related mitochondrial DNA deletion in rat liver depends on dietary fat unsaturation

J. Gerontol. A Biol. Sci. Med. Sci.

Original Contribution
Age-related changes in brain mitochondrial DNA deletion and oxidative stress are differentially modulated by dietary fat type and coenzyme Q₁₀