AGE-DEPENDENT MODIFICATIONS IN THE METABOLISM OF MEVALONATE PATHWAY LIPIDS IN RAT-BRAIN

The levels and rates of biosynthesis of mevalonate pathway lipids in r at brain were investigated during development and aging. Between birth and 18 months of age there are only moderate decreases in the phospho lipid and cholesterol contents but an increase in the levels of dolich yl-P and, particularly of dolichol. The amount of ubiquinone is unchan ged. The rate of incorporation of [H-3]leucine into protein decreases by 10% during the first year, while the incorporation of [H-3]glycerol into phospholipids decreases by 20%. The high rates of [3H]mevalonate incorporation into cholesterol and dolichol after birth decreases rap idly. In contrast, the rate of incorporation into ubiquinone is consta nt. Squalene synthase activity decreases rapidly in the early postnata l period and at 18 months of age this activity is 10-fold lower than i mmediately after birth. cis-Prenyltransferase activity is also high du ring the first postnatal month and reaches a constant level at 4 month s of age. Significantly, nonaprenyl 4-hydroxybenzoate transferase acti vity is high during the entire period investigated. The rate of lipid peroxidation does not change during aging. These results demonstrate t hat brain cholesterol and dolichol exhibit a low rate of turnover duri ng aging, whereas ubiquinone is synthesized at a high rate and exhibit s rapid turnover throughout the entire lifespan.