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Aging is associated with low thyroid state and organ-specific sensitivity to thyroxine.
Thyroid 29, 1723-1733 (2019)
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.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Aging ; Hpt-axis ; Mice ; Thyroid Gland ; Thyroid Hormones; Subclinical Hypothyroidism; Cardiovascular Events; Hyperthyroidism; Age; Guidelines; Mortality; Hormones; Gland; Old; Sex
ISSN (print) / ISBN
1050-7256
e-ISSN
1557-9077
Journal
Thyroid
Quellenangaben
Volume: 29,
Issue: 12,
Pages: 1723-1733
Publisher
Mary Ann Liebert
Publishing Place
140 Huguenot Street, 3rd Fl, New Rochelle, Ny 10801 Usa
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
PPM-MEX-Molecular EXposomics (MEX)