A delicate balance on thyroid hormones controls metabolic health and longevity in mice

An inverse correlation between circulating thyroid hormone levels and longevity has been reported in several species and reduced thyroid hormone levels have been proposed as a biomarker for healthy aging and metabolic fitness in humans. However, hypothyroidism is a serious medical condition associated with reduced health and life expectancy. In this report, we show that severe and even subtle modulations on thyroid hormone levels leading to different forms of hyperthyroidism and hypothyroidism produce an overall unhealthy status and reduced lifespan in mice. A mild reduction in circulating T4 levels (~10%) resulted in hepatic mitochondrial dysfunction, increased ROS production and oxidative damage accumulation. These actions may contribute to the development of metabolic disorders, increased prevalence of hepatocellular carcinomas and early mortality in mice. Our findings raise concerns regarding the development of interventions aiming to modulate thyroid hormones to promote healthy aging or lifespan extension in mammals. Murine pancreatic islets for mWt and Pax8+/- mice were isolated. RNA was extracted and hybridized on Affymetrix microarrays. We sought to obtain the transcriptional profile of pancreatic islets of Wt and Pax8 +/- mice .