Lipid peroxidation in relation to ageing and the role of endogenous aldehydes in diabetes and other age-related diseases

Lipid intermediates which are generated by ROS have drawn more attention after it was found that lipid peroxidation and lipid-radical cycles are two alternative processes. In biological membranes alpha-tocopherol and cytochrome b5, as known, act synergistically to overcome free radical injury and to form lipid-radical cycles. These cycles activate membrane proteins, protect membrane lipids from oxidation and prevent from formation of endogenous aldehydes. Experimental and clinical evidence accumulated for 5-6 years suggests that endogenous aldehydes, such as malonic dialdehyde (MDA) and methylglyoxal (MG), are the major initiators of the metabolic disorders. The age-related diseases emerge when cells cannot control formation of aldehydes and/or cannot abolish the negative effect of methylglyoxal on their metabolism. If the efficiency of the glyoxalase system is insufficient toxic aldehydes cause cumulative damage over a lifetime. In this paper, we provide evidence to consider ageing as a process in which lipid-radical cycles gradually substitute for lipid peroxidation. There are always two opposing tendencies or actions which counteract each other actions of melatonin, lipid-radical cycles and the glyoxalase system (anti-ageing effect) and negative actions of the toxic aldehydes (pro-ageing effect). Life span is determined by the balance of two opposing processes. (C) 2009 Elsevier Ireland Ltd. All rights reserved.