Age-associated changes in dolichol and dolichyl phosphate metabolism in the kidneys and liver of mice

Abstract

The total amounts of cholesterol, dolichol and dolichyl phosphate (Dol-P) in kidneys and liver from 1- and 24-month-old mice were measured after saponification of the tissues. The cholesterol content of kidneys decreased by about 4-fold per g of tissue between the two ages, while the amount of cholesterol/g liver remained constant. The dolichol content of both tissues increased by about 2-fold. The amount of Dol-P in kidneys increased by 7-fold over 23 months, while the concentration in liver decreased some 6-fold. Metabolic labelling experiments using tritiated water demonstrated that the rate of synthesis of total dolichol (dolichol + Dol-P) in the kidneys did not change as a function of age. However, the kidneys of young mice incorporated 3-fold more radioactivity into dolichol than Dol-P, whereas this distribution was reversed in old mice. In liver, the rate of dolichol synthesis decreased 2-fold over 23 months. It was not possible to compare the rates of Dol-P biosynthesis between ages as Dol-P was undetectable in liver of old mice. The relative abundance of the 19 isoprene unit homologs of both dolichol and Dol-P decreased approx. 5% while the 17 isoprene unit homologs increased by a similar amount in both tissues of the old mice.