Inadequate control of thyroid hormones sensitizes to hepatocarcinogenesis and unhealthy aging

被引：12

作者：

Lopez-Noriega, Livia ^{[1
]}

Capilla-Gonzalez, Vivian ^{[1
]}

Cobo-Vuilleumier, Nadia ^{[1
]}

Martin-Vazquez, Eugenia ^{[1
]}

Isabel Lorenzo, Petra ^{[1
]}

Martinez-Force, Enrique ^{[2
]}

Soriano-Navarro, Mario ^{[3
]}

Garcia-Fernandez, Maria ^{[4
,5
]}

Yanina Romero-Zerbo, Silvana ^{[6
]}

Javier Bermudez-Silva, Francisco ^{[6
]}

Diaz-Contreras, Irene ^{[1
]}

Sanchez-Cuesta, Ana ^{[7
,8
]}

Santos-Ocana, Carlos ^{[7
,8
]}

Hmadcha, Abdelkrim ^{[1
]}

Soria, Bernat ^{[6
,9
]}

Martin, Franz ^{[1
,6
]}

Raymond Gauthier, Benoit ^{[1
,6
]}

Martin-Montalvo, Alejandro ^{[1
]}

机构：

[1] Univ Seville, CSIC, Univ Pablo de Olavide, Dept Regenerat & Cell Therapy,Andalusian Ctr Mol, Seville, Spain

[2] Univ Pablo de Olavide, Inst Grasa CSIC, Seville, Spain

[3] Ctr Invest Principe Felipe, Valencia, Spain

[4] Univ Malaga, Biomed Res Inst Malaga IBIMA, Dept Human Physiol, Malaga, Spain

[5] Hosp Reg Univ Malaga, UGC Endocrinol & Nutr, Inst Invest Biomed Malaga IBIMA, Malaga, Spain

[6] Inst Salud Carlos III, Biomed Res Network Diabet & Related Metab Dis CIB, Madrid, Spain

[7] Univ Pablo de Olavide, Ctr Andaluz Biol Desarrollo, Seville, Spain

[8] CIBERER, Alicante, Spain

[9] Univ Miguel Hernandez, Sch Med Sant Joan dAlacant, Dept Physiol, Alicante, Spain

来源：

AGING-US | 2019年 / 11卷 / 18期

关键词：

lifespan; healthspan; thyroid hormones; hyperthyroidism; hypothyroidism; glucose metabolism; FAMILIAL LONGEVITY; SUBCLINICAL HYPOTHYROIDISM; TRIIODOTHYRONINE LEVELS; CALORIC RESTRICTION; FATTY-ACIDS; LIFE-SPAN; EXPRESSION; MICE; CELLS; RISK;

D O I：

10.18632/aging.102285

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：7746 / 7779

页数：34

共 64 条

[1] MAFA and T3 Drive Maturation of Both Fetal Human Islets and Insulin-Producing Cells Differentiated From hESC [J].