Mecanismes d'acció de diferents tipus d'intervencions nutricionals sobre l'estrès oxidatiu i les seves implicacions en el procés fisiològic de l'envelliment

Resumen

The basic chemical process underlying aging was first advanced by Denham Harman in 1956 with the free radical theory of aging. The reaction of active free radicals, normally produced in the organisms, together with cellular constituents, initiates the changes associated with aging. The involvement of free radicals in aging is related to their key role in the origin and evolution of life. Nowadays, the available information shows that the specific composition of tissue macromolecules (proteins, nucleic acids, lipids and carbohydrates) in long-lived animal species gives them an intrinsically high resistance to modification that likely contributes to the superior longevity of these species, which also show a reduced rate of production of free radicals and endogenous oxidative damage. However, the correlation between maximum longevity and lower oxidative stress condition is necessary but not sufficient to validate a theory of aging, because correlation does not necessarily mean that it has to be a cause-effect relationship. Calorie restriction (CR) is the best known experimental manipulation that decreases the rate of aging and increases the maximum longevity in species ranging from invertebrates to vertebrates. It also has beneficial effects in health of mice, rats, primates and humans. Recent findings challenge the traditional consensus that the reduction in caloric intake by itself is the cause of increased longevity in the CR. It is known that protein restriction (PR) and methionine restriction (MetR) mimic the effects of CR, producing 50% of the CR effect in increasing longevity. However, the molecular mechanisms responsible for this effect are unknown. The aim of this study has been to elucidate the factors causing the reduction of oxidative stress and the mean and maximum longevity increase during the CR, in order to try to unravel some of the fundamental mechanisms of aging. In the present work, we have used different kinds of nutritional interventions in Wistar rats, like a 40% of PR, 40% and 80% of MetR, 40% of amino acids restriction except methionine, and finally, a methionine supplementation. Results show that protein and methionine restriction induce a significant decrease in endogenous oxidative molecular damage at the level of mitochondrial DNA and protein injury, derived from glyco and lipoxidative damage. These interventions also produce changes in the amino acid composition, showing a decrease in the susceptibility to lipid peroxidation. The MetR also shows an increase of proteins related to mitochondrial biogenesis, which is accompanied by a decrease in mitochondrial complexes, which produce the reactive oxygen species (ROS), suggesting increased mitochondrial efficiency. All these results place the methionine as a key aminoacid to modulate oxidative stress and longevity in rodents.