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Aging (Albany NY). 2019 Sep 13;11(18):7746-7779. doi: 10.18632/aging.102285. Epub 2019 Sep 13.

Inadequate control of thyroid hormones sensitizes to hepatocarcinogenesis and unhealthy aging.

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Department of Regeneration and Cell Therapy, Andalusian Center for Molecular Biology and Regenerative Medicine-CABIMER, Junta de Andalucia-University of Pablo de Olavide-University of Seville-CSIC, Seville, Spain.
Instituto de la Grasa (CSIC), Universidad Pablo de Olavide, Sevilla, Spain.
Centro de Investigación Príncipe Felipe, Valencia, Spain.
Department of Human Physiology, Málaga University, Biomedical Research Institute of Málaga (IBIMA), Málaga, Spain.
Instituto de Investigación Biomédica de Málaga-IBIMA, UGC Endocrinología y Nutrición. Hospital Regional Universitario de Málaga, Málaga, Spain.
Biomedical Research Network on Diabetes and Related Metabolic Diseases-CIBERDEM, Instituto de Salud Carlos III, Madrid, Spain.
Centro Andaluz de Biología del Desarrollo, Universidad Pablo de Olavide and CIBERER, Sevilla, Spain.
Deptartment of Physiology, University Miguel Hernández School of Medicine Sant Joan d'Alacant, Alicante, Spain.


An inverse correlation between 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. However, hypothyroidism is a medical condition associated with compromised health and reduced life expectancy. Herein, we show, using wild-type and the Pax8 ablated model of hypothyroidism in mice, that hyperthyroidism and severe hypothyroidism are associated with an overall unhealthy status and shorter lifespan. Mild hypothyroid Pax8 +/- mice were heavier and displayed insulin resistance, hepatic steatosis and increased prevalence of liver cancer yet had normal lifespan. These pathophysiological conditions were precipitated by hepatic mitochondrial dysfunction and oxidative damage accumulation. These findings indicate that individuals carrying mutations on PAX8 may be susceptible to develop liver cancer and/or diabetes and raise concerns regarding the development of interventions aiming to modulate thyroid hormones to promote healthy aging or lifespan in mammals.


glucose metabolism; healthspan; hyperthyroidism; hypothyroidism; lifespan; thyroid hormones

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