Effects of age on glycogen synthase and phosphorylase activities in rat liver

The activities of glycogen synthase and phosphorylase were determined in homogenates and subcellular fractions of liver from young adult (6 months' old), adult (12 months' old) and aged (24 months' old) rats. The specific activities (enzyme activity expressed as units per mg protein) of the active form of glycogen synthase (synthase a) as well as of total synthase (synthase a + b) were significantly lower in liver homogenates of aged compared to young adult or adult rats. The age-associated decrease in the specific activity of synthase a was most marked in the 10 000 g and 100 000 g particulate fractions of liver. The specific activities of the active form of phosphorylase (phosphorylase a) as well as of total phosphorylase (phosphorylase a + b) were also significantly lower in liver homogenates of aged compared to young adult or adult animals. The age-related decrease in the specific activity of phosphorylase a was most pronounced in the 10 000 g particulate fraction of liver. Analysis of the specific activity ratios of glycogen synthase a/glycogen synthase a + b indicated a disproportionately greater age-related decrement in the active form of this enzyme. No such age-related difference was evident in the specific activity ratios of phosphorylase a/phosphorylase a + b. The age-associated decrease in the activities of glycogen synthase (a or a + b) and phosphorylase (a or a + b) was also discernible when the enzyme activities were expressed as units per g liver; this decrement in enzyme activity was reflected in all subcellular fractions examined. The levels of plasma insulin, plasma glucose and liver glycogen were not significantly different in rats of the three age groups used in these studies. The reduced activities of liver glycogen synthase and phosphorylase in aged rats is indicative of a likely diminution in the turnover of glycogen in liver during aging. Such an age-associated deficit in liver glycogen metabolism may contribute, at least in part, to the generally observed glucose intolerance upon aging.