Plasmalogens (Pls) are phospholipids containing a vinyl-ether bond at the sn-1 position of the glycerol backbone. They represent between 1/2 and 2/3 of the ethanolamine phospholipids in the brain. During aging, the Pis content in human brain falls down. However, the role of Pis metabolism-related enzymes in the regulation of Pis levels remains to be determined. Dihydroxyacetone phosphate acyltransferase (DHAPAT) is the enzyme involved in the first step of Pls biosynthesis. In the brain, a phospholipase A(2), which selectively acts on Pis, has been isolated (Pls-PLA(2)s). In this work, we aimed to evaluate the impact of DHAP-AT (a key enzyme of Pis biosynthesis) and Pls-PLA(2) (a specific Pis degradation enzyme) on the evolution of Pis content in the rat brain during aging. The influence of n-3 fatty acid intake was also evaluated. Littermates from two generations of n-3 deficient rats were fed an equilibrated diet containing either alpha-LNA alone or with two doses of DHA. After weaning, 3.9 or 21 months of diet, rats were sacrificed. Enzymatic assays were performed, Pis levels were assessed and the sn-2 position of ethanolamine Pis was analyzed. DHAP-AT activity significantly increased between weaning and 3 months with a concomitant increase of brain Pis, which reached maximal levels after 9 months. Then, Pis levels and DHAP-AT activity significantly decreased while Pls-PLA(2)s activity significantly increased. Dietary n-3 fatty acids had no effect on DHAP-AT activity and on Pis levels. In conclusion, the increase of brain Pis content in the first part of the life may be related to the high increase of DHAP-AT activity, probably stimulated by DHA. In aged animals, the decrease of Pis levels may mainly be caused to an increase of their degradation by Pls-PLA2. Dietary DHA may not oppose the physiologic aging (C) 2005 Elsevier SAS. All rights reserved.