Reversal of age-related changes in microsomal enzyme activities following the administration of triamcinolone, triiodothyronine and phenobarbital

Abstract

1. 1. Microsomes were isolated from the livers of 3- and 24-month-old Fischer rats, and specific activities were determined for glucose-6-phosphatase, NADPH cytochrome c reductase, NADPH diaphorase, NADH cytochrome c reductase, NADH diaphorase and NADH neotetrazolium reductase. 2. 2. In agreement with other reports the specific activities of glucose-6-phosphatase and NADPH cytochrome c reductase decreased in the old animals, and NADH cytochrome c reductase increased. 3. 3. Chronic administration of low doses of triamcinolone almost doubled the specific activity of glucose-6-phosphatase in old animals, but caused essentially no change in young animals. In contrast, treatment with phenobarbital halved this activity in young animals, but was essentially without effect in old animals. Treatment with triiodothyronine and caused a marked stimulation of this activity in both young and old animals. 4. 4. There was very little change in the specific activity of NADPH cytochrome c reductase or NADPH diaphorase following these treatments. 5. 5. NADH cytochrome c reductase, NADH neotetrazolium reductase and NADH diaphorase activities were greatly decreased in both young and old animals by administration of all three compounds. 6. 6. Age-related differences in the activity of these enzymes were either diminished or reversed following each treatment. Old animals were as responsive to these stimuli as young animals, and the highest and lowest specific activities observed for each enzyme during the course of all experiments were very similar for young and old animals of the same sex. These observations suggest that age-related differences in these enzyme activities are probably caused by a different metabolic or endocrine state in young and old animals or their hepatocytes, and not by a deterioration of the integrity or control of the synthesis of these proteins.