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Aging is associated with low thyroid state and organ specific sensitivity to thyroxine.
Thyroid 2019T

Abstract

BACKGROUND

Serum thyroid state in the elderly correlates with extended longevity. We hypothesized that age impacts systemic, but also organ-specific thyroid state and response to thyroxine (T4).

METHODS

Young (3 months) and old (23 months) male mice were analysed at baseline and after acute T4 challenge. Age effects on circulating thyroid stimulating hormone (TSH) and thyroid hormone (TH) concentrations, transcript expression in the pituitary and thyroid were compared to organ-specific response 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 vs. 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. 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 reduced activity of the aged thyroid is responsible for the systemic low TH state in old mice. Furthermore, 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 elderly patients to avoid overtreatment.

Authors+Show Affiliations

University Hospital Essen, University Duisburg-Essen, Department of Endocrinology, Metabolism and Diabetes, Hufelandstr.55, Essen, Germany, 45122; helena.rakov@uk-essen.de.Helmholtz Zentrum München-German Research Center for Environmental Health (GmbH), Molecular EXposomics, Munich, Germany; meri.deangelis@helmholtz-muenchen.de.Charité- Universitätsmedizin Berlin, Institut für Experimentelle Endokrinologie, Augustenburger Platz 1, Berlin, Berlin, Germany, 13353; kostja.renko@charite.de.University Hospital Essen, University Duisburg-Essen, Department of Endocrinology, Metabolism and Diabetes, Essen, Germany; sebastian.hoenes@uk-essen.de.University Hospital Essen, University Duisburg-Essen, Department of Endocrinology, Metabolism and Diabetes, Essen, Germany; denise.zwanziger@uk-essen.de.University Hospital Essen, University Duisburg-Essen, Department of Endocrinology, Metabolism and Diabetes, Essen, Germany; lars.moeller@uni-due.de.Helmholtz Zentrum München-German Research Center for Environmental Health (GmbH), Molecular EXposomics, Munich, Germany. Technische Universität München, Department für Biowissenschaftliche Grundlagen, Munich, Germany; schramm@helmholtz-muenchen.de.University Hospital Essen, University Duisburg-Essen, Department of Endocrinology, Metabolism and Diabetes, Essen, Germany; dagmar.fuehrer@uk-essen.de.

Pub Type(s)

Journal Article

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, 2019.
Rakov H, De Angelis M, Renko K, et al. Aging is associated with low thyroid state and organ specific sensitivity to thyroxine. Thyroid. 2019.
Rakov, H., De Angelis, M., Renko, K., Hoenes, S., Zwanziger, D., Moeller, L. C., ... Fuehrer, D. (2019). Aging is associated with low thyroid state and organ specific sensitivity to thyroxine. Thyroid : Official Journal of the American Thyroid Association, doi:10.1089/thy.2018.0377.
Rakov H, et al. Aging Is Associated With Low Thyroid State and Organ Specific Sensitivity to Thyroxine. Thyroid. 2019 Aug 23; 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 - Hoenes,Sebastian, AU - Zwanziger,Denise, AU - Moeller,Lars Christian, AU - Schramm,Karl-Werner, AU - Fuehrer,Dagmar, Y1 - 2019/08/23/ PY - 2019/8/24/entrez JF - Thyroid : official journal of the American Thyroid Association JO - Thyroid N2 - BACKGROUND: Serum thyroid state in the elderly correlates with extended longevity. We hypothesized that age impacts systemic, but also organ-specific thyroid state and response to thyroxine (T4). METHODS: Young (3 months) and old (23 months) male mice were analysed at baseline and after acute T4 challenge. Age effects on circulating thyroid stimulating hormone (TSH) and thyroid hormone (TH) concentrations, transcript expression in the pituitary and thyroid were compared to organ-specific response 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 vs. 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. 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 reduced activity of the aged thyroid is responsible for the systemic low TH state in old mice. Furthermore, 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 elderly patients 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 -