Related Experiment Video
Updated: Jun 19, 2026
04:39
Generation of a Mouse Spontaneous Autoimmune Thyroiditis Model
Published on: March 17, 2023
Genetic predisposition to elevated serum thyrotropin is associated with exceptional longevity.
Gil Atzmon1, Nir Barzilai, Martin I Surks
1Division of Endocrinology, Department of Medicine, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
The Journal of Clinical Endocrinology and Metabolism
|October 20, 2009
Summary
Offspring of exceptionally long-lived individuals exhibit higher thyroid-stimulating hormone (TSH) levels, a heritable trait. Specific TSH receptor (TSHR) gene variants are linked to increased TSH and longevity.
Area of Science:
- Genetics
- Endocrinology
- Gerontology
Background:
- Exceptional longevity in humans is linked to elevated serum thyroid-stimulating hormone (TSH).
- Understanding the genetic and phenotypic basis of longevity is crucial for public health.
- The role of TSH in human aging and lifespan requires further investigation.
Purpose of the Study:
- To investigate if offspring of centenarians have elevated serum TSH.
- To determine the heritability of serum TSH levels.
- To examine the association between specific single nucleotide polymorphisms (SNPs) in the TSH-B and TSH receptor (TSHR) genes and the longevity phenotype.
Main Methods:
- Serum TSH and free T4 levels were measured in Ashkenazi Jewish centenarians, their offspring, and age-matched controls.
- TSH heritability and distribution were analyzed.
- Association studies were conducted for SNPs in the TSH-B and TSHR genes with serum TSH and longevity.
Main Results:
- Offspring of centenarians exhibited significantly higher median serum TSH compared to controls (P=0.02).
- TSH heritability was estimated at 0.33 (P=0.004).
- Specific TSHR SNPs (rs10149689 and rs12050077) and a GA haplotype were more frequent in centenarians and their offspring, associated with increased TSH.
Conclusions:
- A heritable phenotype of raised serum TSH is associated with human longevity.
- Carriers of specific TSHR SNPs (rs12050077 and rs10149689) demonstrate higher serum TSH.
- These genetic variations may contribute to decreased thyroid function and enhanced longevity.
Related Concept Videos
01:25Hyperthyroidism I: Introduction
Hyperthyroidism is a type of thyrotoxicosis characterized by the thyroid gland's overproduction of the thyroid hormones triiodothyronine (T3) and thyroxine (T4). This hormone excess increases the basal metabolic rate and enhances sensitivity to catecholamines.DiagnosisDiagnosis is based on clinical features and biochemical testing. It typically shows suppressed thyroid-stimulating hormone (TSH) levels below 0.4 mIU/L, with elevated free T3 and/or T4. Additional tests, including thyroid...
01:27Hyperthyroidism II: Pathophysiology
Hyperthyroidism is a hypermetabolic state caused by elevated levels of thyroid hormones, triiodothyronine (T3) and thyroxine (T4). It results from dysregulation at the thyroid, pituitary, or immune system level and affects multiple organ systems.PathophysiologyThe most common cause of hyperthyroidism is Graves’ disease, an autoimmune disorder in which antibodies, specifically thyroid-stimulating antibodies (TSAb), a subtype of TSH receptor antibodies (TRAb), bind to and activate TSH receptors...
01:28Graves' Disease I: Introduction
Graves' disease is an autoimmune disorder that causes hyperthyroidism, or overactivity of the thyroid gland. It results from autoantibodies called thyroid-stimulating immunoglobulins (TSIs), which bind to thyroid-stimulating hormone (TSH) receptors, leading to overstimulation of hormone production and a hypermetabolic state.EtiologyAlthough considered idiopathic, Graves’ disease has well-established contributing factors. There is a strong genetic component, with increased prevalence in...
01:11Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
01:24Graves Disease II: Pathophysiology
Graves’ disease is an autoimmune disorder characterized by the production of thyroid-stimulating immunoglobulins (TSI) that activate TSH receptors, leading to excessive synthesis and release of thyroid hormones (T3 and T4) and resulting in hyperthyroidism.Among all causes of hyperthyroidism, Graves’ disease is the most common and can happen at any age, though it is more frequent in women. It produces a hypermetabolic state with features such as weight loss, tachycardia, tremor, and heat...
01:27Goiter
Goiter refers to an abnormal enlargement of the thyroid gland that may appear as a diffuse goiter (uniform enlargement) or nodular (single or multiple nodules). Functionally, it is classified as nontoxic (normal/low hormone levels) or toxic (excess hormone production).PathophysiologyDiffuse thyroid enlargement typically results from prolonged stimulation by thyroid-stimulating hormone (TSH) or TSH-like agents, commonly seen in hypothyroidism or iodine deficiency. In contrast, in hyperthyroid...