Lipid Peroxidation and Membrane Aging

This critique points out that a number of possible alterations in cell metabolism could lead to changes in membrane structure and that the observed effects might not necessarily play a primary role in the physiology of aging. Experimental approaches, while not simple, should distinguish causes of altered membrane asymmetry from its consequences. THE idea that cross-linking agents might play a role in the aging process arose initially from studies on the tanning of animal hides and later from research on the synthesis of organoplastics [1]. That malondialdehyde could be the cross-linking agent produced in vivo from the peroxidation of polyunsaturated fatty acids also came first from industry, as a result of investigations on the rancidity of foodstuffs. The theory proposed by Schroeder [8] states further that the cross-linking somehow leads to loss of membrane asymmetry and that this deficit accounts for the pathophysiologi-cal changes seen in aging. In regard to the possibility that malondialdehyde is an endogenous cross-linker, additional support comes from studies indicating that temporal changes in erythrocyte membranes may be accounted for by malon-dialdehyde production [4]. Also, the detection of ethane and pentane in the breath are indications of the in vivo peroxida-tion of to3 and to6 fatty acids, respectively [7,9], and will also result in malondialdehyde production. Nevertheless, the contribution of other products of lipid peroxidation to the initiation of degenerative processes should be considered. For example, free radicals, which could lead to tissue damage , are generated. Also, the lysophospholipids produced following fatty acid release may also have detrimental effects. Oxidation or peroxidation products of other lipids such as the terpenoids, should additionally be considered. Bat-ten's disease is often referred to as a model for aging of the nervous system, since lipofuscin is produced. In this instance , altered dolichol metabolism has been reported [5]. A peroxidase defect has also been described in this disease, but the claim is at present controversial. Oxidized cholesterol may also have deleterious effect on membranes. The presence of 25-hydroxycholesterol in the diet has been reported to produce vascular damage [6]. If malondialdehyde indeed proves to be the culprit, Schroeder's theory would be sharpened by a proposal for precisely how it produces its damage. While it can cross-link amino groups of phos-phatidylethanolamine and phosphatidylserine, malondial-dehyde can also cross-link proteins. The cross-linking of such important proteins as ankyrin or spectrin (fodrin in the nervous system) would seem to suffice to limit membrane …