Journal of Bioenergetics and Biomembranes

, Volume 37, Issue 2, pp 83–90 | Cite as

Dietary Restriction at Old Age Lowers Mitochondrial Oxygen Radical Production and Leak at Complex I and Oxidative DNA Damage in Rat Brain

  • Alberto Sanz
  • Pilar Caro
  • Jorge Ibañez
  • José Gómez
  • Ricardo Gredilla
  • Gustavo Barja


Previous studies in mammalian models indicate that the rate of mitochondrial reactive oxygen species ROS production and the ensuing modification of mitochondrial DNA (mtDNA) link oxidative stress to aging rate. However, there is scarce information concerning this in relation to caloric restriction (CR) in the brain, an organ of maximum relevance for ageing. Furthermore, it has never been studied if CR started late in life can improve those oxidative stress-related parameters. In this investigation, rats were subjected during 1 year to 40% CR starting at 24 months of age. This protocol of CR significantly decreased the rate of mitochondrial H2O2 production (by 24%) and oxidative damage to mtDNA (by 23%) in the brain below the level of both old and young ad libitum-fed animals. In agreement with the progressive character of aging, the rate of H2O2 production of brain mitochondria stayed constant with age. Oxidative damage to nuclear DNA increased with age and this increase was fully reversed by CR to the level of the young controls. The decrease in ROS production induced by CR was localized at Complex I and occurred without changes in oxygen consumption. Instead, the efficiency of brain mitochondria to avoid electron leak to oxygen at Complex I was increased by CR. The mechanism involved in that increase in efficiency was related to the degree of electronic reduction of the Complex I generator. The results agree with the idea that CR decreases aging rate in part by lowering the rate of free radical generation of mitochondria in the brain.


Caloric restriction brain mitochondria free radical generation aging old age oxygen radicals Complex I oxidative DNA damage 8-hydroxydeoxyguanosine mitochondrial DNA 





mitochondrial DNA


nuclear DNA




reactive oxygen species


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Copyright information

© Springer Science + Business Media, Inc. 2005

Authors and Affiliations

  • Alberto Sanz
    • 1
  • Pilar Caro
    • 1
  • Jorge Ibañez
    • 1
  • José Gómez
    • 1
  • Ricardo Gredilla
    • 1
  • Gustavo Barja
    • 1
    • 2
  1. 1.Department of Animal Physiology-II, Faculty of Biological SciencesComplutense UniversityMadridSpain
  2. 2.Departamento de Fisiología Animal-II, Facultad de Ciencias BiológicasUniversidad ComplutenseMadridSpain

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