2026-06-14T03:54:04Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/179092024-09-21T22:34:17Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16927

00925njm 22002777a 4500 dc López-Noriega, Livia author Capilla-González, Vivian author Cobo-Vuilleumier, Nadia author Martin-Vazquez, Eugenia author Lorenzo, Petra Isabel author Martinez-Force, Enrique author Soriano-Navarro, Mario author García-Fernández, María author Romero-Zerbo, Silvana Yanina author Bermúdez-Silva, Francisco Javier author Díaz-Contreras, Irene author Sánchez-Cuesta, Ana author Santos-Ocaña, Carlos author Hmadcha, Abdelkrim author Soria, Bernat author Martín, Franz author Gauthier, Benoit Raymond author Martin-Montalvo, Alejandro author 2019-09-13 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. 10.18632/aging.102285 1945-4589 Aging http://hdl.handle.net/10668/14504 31518338 http://hdl.handle.net/20.500.12105/17909 Glucose metabolism Healthspan Hyperthyroidism Hypothyroidism Lifespan Thyroid hormones Inadequate control of thyroid hormones sensitizes to hepatocarcinogenesis and unhealthy aging.