Thermogenesis and longevity in mammals. Thyroxin model of accelerated aging

Development of experimental models of life span regulation is an important goal of modern gerontology. We proposed a thyroxin model of accelerated aging. Male Wistar rats at the age of 17 months received thyroxin in drinking water at a concentration of 6 mg/L for 2 months as a model of induced hyperthyroidism (IH). Administration of thyroxin resulted in a decrease in life span and a 2 degrees C increase in body temperature that was accompanied by a 2 fold increase in thyroxin level and a 40% increase in triiodothyronine in blood serum. Induced hyperthyroidism can be used as a model of accelerated aging. We also found that thyroxin administration acts as uncoupler of oxidative phosphorylation as treatment was accompanied by an increase in the generation of superoxide radicals by 50%. Antioxidant enzyme activity remained unchanged (glutathione peroxidase, glutathione reductase mitochondrial) or was reduced (glutathione-S-transferase by 1.7 times) as compared with the control. The activity of glucose-6-transferase was increased by 2.8 times as compared with control, and malate dehydrogenase activity in liver increased by 6.8 times. Induced hyperthyroidism in rats resulted in distinct epigenotype which was accompanied by a decrease in life span. (C) 2014 Elsevier Inc. All rights reserved.