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.
Dmitriev
L F
LF
Group of Neurobiology, Cardiology Research Center, 121552 Moscow, Russia. leon.d@mail.ru
Titov
V N
VN
D000375:Aging / Q000378:metabolism* / Q000473:pathology; D000447:Aldehydes / Q000378:metabolism*; D005609:Free Radicals / Q000378:metabolism*; D006801:Humans; D007791:Lactoylglutathione Lyase / Q000378:metabolism*; D050356:Lipid Metabolism / Q000502:physiology; D015227:Lipid Peroxidation / Q000502:physiology*; D008659:Metabolic Diseases / Q000378:metabolism / Q000503:physiopathology; D018384:Oxidative Stress / Q000502:physiology*; D011765:Pyruvaldehyde / Q000378:metabolism
D000447:Aldehydes; D005609:Free Radicals; D011765:Pyruvaldehyde; D007791:Lactoylglutathione Lyase