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Aging Is Associated with Low Thyroid State and Organ-Specific Sensitivity to Thyroxine.
Thyroid. 2019 12; 29(12):1723-1733.T

Abstract

Background:

Serum thyroid state in older adults correlates with extended longevity. We hypothesized that age impacts not only systemic but also organ-specific thyroid state and response to thyroxine (T4).

Methods:

Young (3 months) and old (23 months) male mice were analyzed at baseline and after acute T4 challenge. Age effects on circulating thyrotropin (TSH) and thyroid hormone (TH) concentrations, transcript expression in the pituitary and thyroid were compared with organ-specific responses characterized by hepatic and cardiac content of TH and TH metabolites and expression of TH-target genes, as well as hepatic deiodinase 1 activity.

Results:

Circulating TH concentrations and hepatic and cardiac TH content were lower in old versus young mice. After injection with T4, conversion of T4 to triiodothyronine was decreased in old mice while TH transport in liver and heart was not affected. Organ-specific TH response was augmented in old mice in liver but not heart, indicating age- and tissue-specific sensitivity to TH. A compensatory increase of thyroid stimulating hormone subunit beta expression in the pituitary and increased serum TSH concentrations, but reduced expression of thyroid differentiation markers were found in old mice.

Conclusions:

We suggest that a reduced activity of the aged thyroid is responsible for the systemic low TH state in old mice. Further, divergent TH metabolism and tissue response in liver and heart occur after T4 treatment in an aged organism. These rodent data are in agreement with a much narrower window for T4 substitution in the older adults to avoid overtreatment.

Authors+Show Affiliations

Department of Endocrinology, Diabetes and Metabolism; Department of Endocrinology, Diabetes and Metabolism; University Hospital Essen, University Duisburg-Essen, Essen, Germany.Molecular EXposomics, Helmholtz Zentrum München - German Research Center for Environmental Health (GmbH), Neuherberg, Germany.Institut für Experimentelle Endokrinologie, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.Department of Endocrinology, Diabetes and Metabolism; Department of Endocrinology, Diabetes and Metabolism; University Hospital Essen, University Duisburg-Essen, Essen, Germany.Department of Endocrinology, Diabetes and Metabolism; Department of Endocrinology, Diabetes and Metabolism; University Hospital Essen, University Duisburg-Essen, Essen, Germany. Clinical Chemistry-Division of Laboratory Research, Department of Endocrinology, Diabetes and Metabolism; University Hospital Essen, University Duisburg-Essen, Essen, Germany.Department of Endocrinology, Diabetes and Metabolism; Department of Endocrinology, Diabetes and Metabolism; University Hospital Essen, University Duisburg-Essen, Essen, Germany.Molecular EXposomics, Helmholtz Zentrum München - German Research Center for Environmental Health (GmbH), Neuherberg, Germany. Department für Biowissenschaften, Wissenschaftszentrum Weihenstephan für Ernährung, Landnutzung und Umwelt, Technische Universität München, Freising, Germany.Department of Endocrinology, Diabetes and Metabolism; Department of Endocrinology, Diabetes and Metabolism; University Hospital Essen, University Duisburg-Essen, Essen, Germany.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

31441387

Citation

Rakov, Helena, et al. "Aging Is Associated With Low Thyroid State and Organ-Specific Sensitivity to Thyroxine." Thyroid : Official Journal of the American Thyroid Association, vol. 29, no. 12, 2019, pp. 1723-1733.
Rakov H, De Angelis M, Renko K, et al. Aging Is Associated with Low Thyroid State and Organ-Specific Sensitivity to Thyroxine. Thyroid. 2019;29(12):1723-1733.
Rakov, H., De Angelis, M., Renko, K., Hönes, G. S., Zwanziger, D., Moeller, L. C., Schramm, K. W., & Führer, D. (2019). Aging Is Associated with Low Thyroid State and Organ-Specific Sensitivity to Thyroxine. Thyroid : Official Journal of the American Thyroid Association, 29(12), 1723-1733. https://doi.org/10.1089/thy.2018.0377
Rakov H, et al. Aging Is Associated With Low Thyroid State and Organ-Specific Sensitivity to Thyroxine. Thyroid. 2019;29(12):1723-1733. PubMed PMID: 31441387.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Aging Is Associated with Low Thyroid State and Organ-Specific Sensitivity to Thyroxine. AU - Rakov,Helena, AU - De Angelis,Meri, AU - Renko,Kostja, AU - Hönes,Georg Sebastian, AU - Zwanziger,Denise, AU - Moeller,Lars Christian, AU - Schramm,Karl-Werner, AU - Führer,Dagmar, Y1 - 2019/09/26/ PY - 2019/8/24/pubmed PY - 2019/8/24/medline PY - 2019/8/24/entrez KW - HPT-axis KW - aging KW - mice KW - thyroid gland KW - thyroid hormones SP - 1723 EP - 1733 JF - Thyroid : official journal of the American Thyroid Association JO - Thyroid VL - 29 IS - 12 N2 - Background: Serum thyroid state in older adults correlates with extended longevity. We hypothesized that age impacts not only systemic but also organ-specific thyroid state and response to thyroxine (T4). Methods: Young (3 months) and old (23 months) male mice were analyzed at baseline and after acute T4 challenge. Age effects on circulating thyrotropin (TSH) and thyroid hormone (TH) concentrations, transcript expression in the pituitary and thyroid were compared with organ-specific responses characterized by hepatic and cardiac content of TH and TH metabolites and expression of TH-target genes, as well as hepatic deiodinase 1 activity. Results: Circulating TH concentrations and hepatic and cardiac TH content were lower in old versus young mice. After injection with T4, conversion of T4 to triiodothyronine was decreased in old mice while TH transport in liver and heart was not affected. Organ-specific TH response was augmented in old mice in liver but not heart, indicating age- and tissue-specific sensitivity to TH. A compensatory increase of thyroid stimulating hormone subunit beta expression in the pituitary and increased serum TSH concentrations, but reduced expression of thyroid differentiation markers were found in old mice. Conclusions: We suggest that a reduced activity of the aged thyroid is responsible for the systemic low TH state in old mice. Further, divergent TH metabolism and tissue response in liver and heart occur after T4 treatment in an aged organism. These rodent data are in agreement with a much narrower window for T4 substitution in the older adults to avoid overtreatment. SN - 1557-9077 UR - https://www.unboundmedicine.com/medline/citation/31441387/Aging_is_associated_with_low_thyroid_state_and_organ_specific_sensitivity_to_thyroxine L2 - https://www.liebertpub.com/doi/full/10.1089/thy.2018.0377?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -
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