Aging-related decrease in liver peroxisomal fatty acid oxidation in control and clofibrate-treated mice. A biochemical study and mechanistic approach.

Membrane fatty acid composition affects membrane structure and function. Alterations in membrane composition have been reported in old animals and it is now hypothesized that these alterations may contribute to the onset of age-related diseases. Previously, we proposed that peroxisomes might also be involved in these aging-related membrane alterations. In order to extend our previous work, we have assayed acyl-CoA oxidase activity and cyanide-insensitive fatty acid oxidation activity for both arachidonic 20:4(n-6) and docosahexaenoic 22:6(n-3) acids, catalase and urate oxidase activities, microsomal cytochrome P450 content and cytochrome P4504A1 laurate hydroxylase activity in the liver of young and old mice fed either a control or a clofibrate-supplemented diet. Our results suggest a progressive general decrease in peroxisomal function during aging, including a decrease in the fatty acid oxidation pathway that takes place via a specific decrease in acyl-CoA oxidase activity. The aging-related decrease in peroxisomal function is linked to a concomitant decrease in cytochrome P4504A laurate hydroxylase activity in control animals but not in clofibratetreated mice. This suggests aging impairs a mechanism in peroxisome proliferation that is subsequent to the cytochrome P4504A step. Implications of the aging-related peroxisomal fatty acid oxidation decrease on health through possible alterations in membrane composition and function and very long chain fatty acid accumulation are discussed.