Longevity and aging. Role of free radicals and xanthine oxidase. A review

Longevity and aging are differently regulated. Longevity has an important part of genetic determinants, aging is essentially post-genetic. Among the genes involved in longevity determination, sirtuins, activated also by calorie restriction and some others as the TOR pathway, attracted special interest after the insulin-IGF pathway first shown to regulate longevity in model organisms. For most of these genes, postponement of life-threatening diseases is the basis of their action which never exceeds about 35% of all determinants, in humans. Among the post-genetic mechanisms responsible for age-related decline of function, free radicals attracted early interest as well as the Maillard reaction, generating also free radicals. Most attempts to remediate to free radical damage failed however, although different scavenger mechanisms and protective substances are present in the organism. Synthetic protectors were also tested without success. The only example of a successful treatment of a free radical mediated pathology is the case of xanthine oxidase, involved in cardiovascular pathology, essentially during the ischemia-reperfusion process. Its inhibition by allopurinol is currently used to fight this deadly syndrome. (C) 2014 Elsevier Masson SAS. All rights reserved.