Effects of aging on the composition and metabolism of docosahexaenoate-containing lipids of retina.

The amount of docosahexaenoate (22:6n-3)-containing phospholipid species decreases with aging in the rat retina. Most lipids, but especially choline and serine glycerophospholipids, show a significant fall in 22:6n-3, which is not compensated by increases in other polyenoic fatty acids. The decrease not only affects 22:6 but also various very long chain n-3 hexaenoic fatty acids which, in phosphatidylcholine, have up to 36 carbon atoms, and which are probably synthesized by successive elongations of 22:6n-3. The in vitro incorporation of [2-3H]glycerol into retinal lipids indicates that the de novo biosynthetic pathways are not impaired by aging. The incorporation of [1-14C]docosahexaenoate is significantly stimulated into all lipids of aged retinas, but to the largest extent in those showing the largest decreases in 22:6, especially in choline glycerophospholipids. The results indicate that the decreased levels of 22:6 with aging are due not to an impaired activity of the enzymes involved in the synthesis and turnover of phospholipids but to a decreased availability of this polyene in the retina. It is suggested that this may stem from a defect in some of the enzymatic steps that lead to the synthesis of 22:6n-3, probably that catalyzed by delta 4 desaturase, the effect on longer hexaenes being secondary to the decreased synthesis of 22:6.