Lipid peroxidation in aging and age-dependent diseases

Aging is related with an increase in oxidation products derived from nucleic acids, sugars, sterols and lipids. Evidence will be presented that these different oxidation products are generated by processes induced by changes in the cell membrane structure (CMS), and not by superoxide, as commonly assumed. CMS activate apparently membrane bound phospholipases A2 in mammals and plants. Such changes occur by proliferation, aging and especially by wounding. After activation of phospholipases, influx of Ca2+ ions and activation of lipoxygenases (LOX) is induced. The LOX transform polyunsaturated fatty acids (PUFAs) into lipid hydroperoxides (LOOHs), which seem to be decomposed by action of enzymes to signalling compounds. Following severe cell injury, LOX commit suicide. Their suicide liberates iron ions that induce nonenzymic lipid peroxidation (LPO) processes by generation of radicals. Radicals attack all compounds with the structural element -CH=CH-CH(2)-CH=CH-. Thus, they act on all PUFAs independently either in free or conjugated form. The most abundant LPO products are derived from linoleic acid. Radicals induce generation of peroxyl radicals, which oxidise a great variety of biological compounds including proteins and nucleic acids. Nonenzymic LPO processes are induced artificially by the treatment of pure PUFAs with bivalent metal ions. The products are separable after appropriate derivatisation by gas chromatography (GC). They are identified by electron impact mass spectrometry (EI/MS). The complete spectrum of LPO products obtained by artificial LPO of linoleic acid is detectable after wounding of tissue, in aged individuals and in patients suffering from age-dependent diseases. Genesis of different LPO products derived from linoleic acid will be discussed in detail. Some of the LPO products are of high chemical reactivity and therefore escape detection in biological surrounding. For instance, epoxides and highly unsaturated aldehydic compounds that apparently induce apoptosis.