Inadequate control of thyroid hormones sensitizes to hepatocarcinogenesis and unhealthy aging


For Aging’s Volume 11, Issue 18, the Journal devoted the Cover to a research paper by Dr. Alejandro Martin-Montalvo from the 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, Sevilla, Spain

Herein, the authors 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.

Dr. Martin-Montalvo said, "The increasing burden of age-related diseases highlights the importance of uncovering the mechanisms underlying the aging process."

TSH stimulates the production of T4 and T3 in the thyroid gland, which in turn inhibit both TRH and TSH synthesis when THs reach the hypothalamus and hypophysis, respectively.

Greater life expectancy has been associated with reduced circulating levels of T4, T3, and/or high TSH levels in both animal models and humans.

In this line, the Laron, Ames and Snell dwarf mice, which have reduced GH signalling and reduced circulating TH levels, exhibit a consistent exceptional lifespan as well as other metabolic alterations such as enhanced hepatic insulin sensitivity.

Both rodents and humans under calorie restriction, which comprises a variety of nutritional interventions with several beneficial effects including extended longevity, exhibit reduced circulating T3 levels and/or high TSH levels.

Likewise, nonagenarians from families with exceptional long lifespans, as well as their descendants, have been reported to exhibit increased TSH levels and/or decreased circulating T3 levels.

The Martin-Montalvo research team concluded, "In 1908 Dr. Max Rubner proposed the rate of living theory of aging and longevity, postulating that species with a low metabolic rate would have increased life expectancy when compared to species with a higher metabolic rate.

In this line, restricted levels of THs, which control the metabolic rate, have been associated with increased longevity as well as metabolic fitness."

Full Text -

Correspondence to: Alejandro Martin-Montalvo; email: and Benoit Raymond Gauthier; email:

Keywords: lifespan, healthspan, thyroid hormones, hyperthyroidism, hypothyroidism, glucose metabolism

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Launched in 2009, Aging (Aging-US) publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways.

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