Free Radicals and Glycoxidative Stress in Ageing and Age‐Related Diseases

Abstract

Abstract. Free radicals and glycoxidative reactions are known to be associated with ageing on the level of the cell and whole organism. Free radicals are ubiquitous in living things and they lead to irreversible reactions in cell organelles and cell metabolism. One important source of free radicals is advanced glycation end products (AGEs) resulting from non‐enzymatic glycation and oxidation of proteins and lipids. Ageing, and thus life span, correlate with free radical generation and antioxidative defense as well as with advanced glycation end products. Most chronic diseases are also associated with free radicals and AGEs. Overproduction of free radicals accelerates cell ageing and is counteracted by antioxidants. Antioxidant status is in part amendable through nutritional and pharmacological interventions. AGE interaction with its receptor contributes also to accelerated ageing in many pathological conditions. Particularly vulnerable are long‐lived proteins, eg. in lens crystallin and skin collagen. The analysis of the mechanism generating free radicals and of the reaction of AGEs with cellular metabolism opens new avenues for the delaying of the development of chronic diseases such as atherosclerosis and neurodegenerative disease. On the other hand, the impact of free radicals on carcinogenesis may differ according to the cancer stage and hence the preventive potential of antioxidants is proposed to be different in early and late stages of cancer development. Free radicals and AGE products are important mediators of age‐related diseases and ageing per se. Intake of antioxidants over the life‐time determines, among other factors, the rate of ageing and the development of degenerative diseases. Interventive strategies such as soluble receptors for AGEs and effective antioxidants might become important therapeutic strategies in the near future.