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