Endocrine Abstracts

Since thyroid hormone is a key regulator of metabolism, changes in thyroid hormone signaling have widespread effects. Thyroid state changes during aging and vice versa lifespan is affected by thyroid state. However, underlying mechanisms remain elusive. DNA damage importantly contributes to the process of aging, as underscored by premature aging syndromes caused by defective DNA repair.

In different mouse models of premature (DNA-repair deficient animals) and normal aging, thyroid hormone signaling is attenuated in specific tissues. This is associated with tissue-specific induction of the thyroid hormone-inactivating deiodinase D3 and decrease of thyroid hormone-activating D1 activities. Also, the T3-receptor beta appears important in mediating the T3-effects on aging. From the current knowledge it can be speculated that tissue-specific attenuated thyroid hormone signaling may contribute to the adaptive survival response during aging.

Future studies should reveal if decreasing thyroid hormone signaling improves survival and if interventions that (further) suppress TH signaling extend lifespan. Such studies on modulating thyroid hormone signaling may have important implications for future therapeutic strategies to promote healthy aging.