Estudio de la xantina oxidasa y otros parámetros de estado redox en el envejecimiento cronológico, prematuro y patológico en raton

Laburpena

The chronic oxidative and inflammatory state underlying the aging process, that affects all physiological systems of the organism, results in a progressive loss of homeostasis and the health. Thus, according to the theory of oxidation proposed by Harman in 1956 to explain how aging occurs, the oxidative stress is caused by increased production of oxidants and / or reduction systems antioxidant defenses, resulting increased oxidative damage in biomolecules (lipids, proteins, DNA), which explains the deterioration of cell functionality associated with the age. In this context, it is proposed that various oxidizing enzymes such as xanthine oxidase (XO), could contribute in a relevant manner to the oxidative stress associated with aging. The XO has been described as a major cytoplasmic source of O2 • - and H2O2, as well as RNS, and plays an important role in the regulation of the cellular redox state, as well as contributes to oxidative stress and chronic inflammation that occur in many diseases associated with aging, however, is not yet clear its role as a prooxidant mechanism in physiological aging. Moreover, there are not studies in which the activity and expression of this enzyme have been characterized along the aging process. Furthermore, although inhibition assays performed with allopurinol, a specific XO inhibitor, demonstrated the involvement of this enzyme in oxidative and inflammatory stress underlying to several pathologies associated with aging (i.e. Hypertension, diabetes, etc.). However, there are no direct studies on the effects of allopurinol on oxidative stress associated with aging. Furthermore, an age-related decline in antioxidant enzymes, such as superoxide dismutase (SOD) and catalase (CAT), has been described, which is is critical to maintaining a good redox balance, as well as to prevent cell damage caused by ROS generated by the XO and other oxidants sources. In this context, it is important to note that previous studies of our laboratory revealed that the higher oxidative stress state observed in leukocytes from old mice, could explain the impaired immune function of these animals. However, immune cells from naturally long-lived animals or centenarians showed preservation of immune function in response to stimuli and controlled oxidative stress and the increased oxidation in these cells. Moreover, in the context of the neuro-immune communication there are several examples of alteration of survival responses, in which an oxidation-inflammation occurs, that accelerates the rate of aging...