Are changes of the cell membrane structure causally involved in the aging process?
Lipid peroxidation is recognized by proliferation, wounding, and aging. The connecting link between these different events is a change in cell wall structure, which activates membrane bound phospholipases. These cleave phospholipids. Thus liberated polyunsaturated fatty acids (PUFAs) are substrates for lipoxygenases, which accept equally well linoleic acid and arachidonic acid and generate lipid hydroperoxides (LOOHs). If the amount of free PUFAs exceeds a certain amount, lipoxygenases commit suicide. The consequence is liberation of free iron ions that react with LOOHs by formation of radicals. These start a chain reaction. LOO* radicals produced in the course of this process attack proteins, nucleic acids, and also double bonds of all unsaturated compounds by epoxidation. Morever LOOHs are decomposed to toxic epoxy acids and alphabetagammadelta-unsaturated aldehydes. Both species react with glutathione. The resulting products seem to induce apoptosis. Since the products generated by wounding or aging are formed by decomposition of LOOHs the investigation of the aging processes can be simplified by studying the physiological action of artificially generated lipid peroxidation products derived from pure PUFAs. Degradation products of LOOHs are generated by thermal decomposition of fat-containing PUFAs. These products are induced into the body by adsorption in the intestine. They are at least partly incorporated in low density lipoproteins (LDLs). Primarily investigations seem to indicate that an overload of a diet rich in PUFAs induces only after two days an increase in oxidized LDL/PUFAs for a factor up to two in young people and for a factor of more than two in old individuals.
Spiteller
Gerhard
G
Organische Chemie, Universität Bayreuth, Universitätsstrasse 30, 95440 Bayreuth, Germany. Gerhard.Spiteller@uni-bayreuth.de
D000375:Aging / Q000502:physiology*; D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology / Q000503:physiopathology; D002462:Cell Membrane / Q000502:physiology* / Q000648:ultrastructure; D004041:Dietary Fats / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D005609:Free Radicals / Q000378:metabolism; D015227:Lipid Peroxidation; D008054:Lipid Peroxides / Q000378:metabolism*; D015394:Molecular Structure; D010084:Oxidation-Reduction
D004041:Dietary Fats; D005231:Fatty Acids, Unsaturated; D005609:Free Radicals; D008054:Lipid Peroxides