Thyroid Hormone Signaling and Homeostasis During Aging

Bowers, James; Terrien, Jérémy; Clerget-Froidevaux, Marie-Stéphanie; Gothié, Jean-David; Rozing, Maarten P.; Westendorp, Rudi G.J.; Heemst, Diana van; Demeneix, Barbara

doi:10.1210/er.2012-1056

Cited by 96 publications

(78 citation statements)

References 380 publications

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“…16 This potential adaptive mechanism could also be a hereditary phenotype that contributes to longevity, since the nonagenarian offspring of centenarians were shown to have higher circulating TSH and lower thyroid hormone concentrations than did the offspring of parents who died at younger ages. 29 …”

Section: Hypothalamic–pituitary–peripheral Organ Axesmentioning

confidence: 99%

The physiology of endocrine systems with ageing

Beld

Kaufman

Zillikens

et al. 2018

The Lancet Diabetes & Endocrinology

200

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During ageing, the secretory patterns of the hormones produced by the hypothalamic–pituitary axis change, as does the sensitivity of the axis to negative feedback by end hormones. Additionally, glucose homoeostasis tends towards disequilibrium with increasing age. Along with these endocrine alterations, a loss of bone and muscle mass and strength occurs, coupled with an increase in fat mass. In addition, ageing-induced effects are difficult to disentangle from the influence of other factors that are common in older people, such as chronic diseases, inflammation, and low nutritional status, all of which can also affect endocrine systems. Traditionally, the decrease in hormone activity during the ageing process has been considered to be detrimental because of the related decline in bodily functions. The concept of hormone replacement therapy was suggested as a therapeutic intervention to stop or reverse this decline. However, clearly some of these changes are a beneficial adaptation to ageing, whereas hormonal intervention often causes important adverse effects. In this paper, we discuss the effects of age on the different hypothalamic–pituitary–hormonal organ axes, as well as age-related changes in calcium and bone metabolism and glucose homoeostasis.

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Section: Hypothalamic–pituitary–peripheral Organ Axesmentioning

confidence: 99%

The physiology of endocrine systems with ageing

Beld

Kaufman

Zillikens

et al. 2018

The Lancet Diabetes & Endocrinology

200

View full text Add to dashboard Cite

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“…Of specific clinical importance is an adequate supply of TH during critical phases of life [4], e.g. in utero and in the neonatal period (for the child), during pregnancy (for the mother) or with older age.…”

Section: Th Dysfunction - a Canonical Definitionmentioning

confidence: 99%

“…However, detection of thyroid function values outside the assay reference ranges must not necessarily indicate a thyroid disorder. For this reason, there have been heated debates on the so-called ‘normal TSH values' for some years on both national and international stages [4,20,21]. Determination of TSH serum concentrations in clinical chemistry largely depends on the assay(s) used and usually manufacturer-derived reference ranges.…”

Section: Laboratory Th Assessmentmentioning

confidence: 99%

Understanding the Healthy Thyroid State in 2015

2015

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Thyroid hormones (TH) are of crucial importance for the physiological function of almost all organs. In cases of abnormal TH signaling, pathophysiological consequences may arise. The routine assessment of a healthy or diseased thyroid function state is currently based on the determination of serum concentrations of thyroid-stimulating hormone (TSH), and the TH T₃ and T₄. However, the definition of a ‘normal' TSH range and similarly ‘normal' T₃ and T₄ concentrations remains the subject of debate in different countries worldwide and has important implications on patient treatment in clinics. Not surprisingly, a significant number of patients whose thyroid function tests are biochemically determined to be within the normal range complain of impaired well-being. The reasons for this are so far not fully understood, but it has been recognized that thyroid function status needs to be ‘individualized' and extended beyond simple TSH measurement. Thus, more precise and reliable parameters are required in order to optimally define the healthy thyroid status of an individual, and as a perspective to employ these in clinical routine. With the recent identification of new key players in TH action, a more accurate assessment of a patient's thyroid status may in the future become possible. Recently described distinct TH derivatives and metabolites, TH transporters, nongenomic TH effects (either through membrane-bound or cytosolic signaling), and classical nuclear TH action allow for insights into molecular and cellular preconditions of a healthy thyroid state. This will be a prerequisite to improve management of thyroid dysfunction, and additionally to prevent and target TH-related nonthyroid disease.

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“…A causal relationship between thyroid function and longevity was further demonstrated by experimental induction of hypothyroidism in rats, which resulted in extended life span. Conversely, inducing hyperthyroidism resulted in significantly shorter life span [4][5][6].…”

Section: Introductionmentioning

confidence: 99%

“…Euthyroid 50 year-old participants with increased levels of TSH had a longer life expectancy than participants with decreased serum TSH levels [4]. Increased TSH levels were also associated with lower mortality in participants between ages 85 and 90 [5] and in their offspring [6], and even in centenarians [7,8]. In fact, increased familial longevity is characterized by higher TSH secretion, without altering whole body energy metabolism [9].…”

Section: Introductionmentioning

confidence: 99%

Adipose TSHB in Humans and Serum TSH in Hypothyroid Rats Inform About Cellular Senescence

Moreno-Navarrete

Liñares-Pose

Sabater

et al. 2018

Cell Physiol Biochem

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Background/Aims: Thyroid hormones have been recently linked to senescence and longevity. Given the recent description of TSHB mRNA in human adipose tissue (AT), we aimed to investigate the relationship between local AT TSH and adipose tissue senescence. Methods: TSHB mRNA (measured by real-time PCR) and markers of adipose tissue senescence [BAX, DBC1, TP53, TNF (real-time PCR), telomere length (Telo TAGGG Telomere Length Assay) and lipidomics (liquid chromatography mass spectrometry)] were analysed in subcutaneous (SAT) and visceral (VAT) AT from euthyroid subjects. The chronic effects of TSH were also investigated in AT from hypothyroid rats and after recombinant human TSH (rhTSH) administration in human adipocytes. Results: Both VAT and SAT TSHB gene expression negatively correlated with markers of AT cellular senescence (BAX, DBC1, TP53, TNF gene expression and specific glucosylceramides) and positively associated with telomere length. Supporting these observations, both rhTSH administration in human adipocytes and increased TSH in hypothyroid rats resulted in decreased markers of cellular senescence (Bax and Tp53 mRNA) in both gonadal and subcutaneous white adipose tissue. Conclusion: These data point to a possible role of TSH in AT cellular senescence.

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Thyroid Hormone Signaling and Homeostasis During Aging

Cited by 96 publications

References 380 publications

The physiology of endocrine systems with ageing

The physiology of endocrine systems with ageing

Understanding the Healthy Thyroid State in 2015

Adipose TSHB in Humans and Serum TSH in Hypothyroid Rats Inform About Cellular Senescence

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