The aged-related increase in xanthine oxidase expression and activity in several tissues from mice is not shown in long-lived animals

Xanthine oxidase (XO) is an important source of oxidant production and plays an essential role in several oxidative stress-related diseases. Aging is associated with a progressive deregulation of homeostasis as a result of a chronic oxidative stress situation. In the present work the age-related changes in XO expression and activity, as well as the activities of superoxide dismutase and catalase have been investigated in liver, kidney and thymus from four different age groups of mice, including long-lived animals. Furthermore, we have evaluated the contribution of the XO to the oxidative stress-associated with aging, in comparison to another enzymatic key source of oxidant generation, the NADPH oxidase, in peritoneal leukocytes from old mice. In all the tissues analyzed, the old mice showed higher activity and expression of XO, and decreased or unchanged superoxide dismutase and catalase activities as compared with adult mice. Moreover, the inhibition of reactive oxygen species with allopurinol or apocynin in peritoneal leukocytes from old mice, suggest that both XO and NADPH oxidase contribute to the generation of superoxide anion, whereas the XO may have a special relevance in the production of hydrogen peroxyde. Finally, long-lived animals showed a well-preserved redox state, in terms of antioxidant defenses and oxidant compounds in tissues and immune cells, which may be related to the ability of these subjects to reach a very advanced age in healthy condition. These results confirm that XO plays an important role in the age-related oxidative stress in tissues and immune cells.