Stimulating one variety of thyroid hormone receptor spurs cellular senescence, Zambrano et al. report. The finding might explain how thyroid hormones accelerate aging and protect against cancer.

Thyroid hormones fire up metabolism by binding to either of two receptors, thyroid hormone receptor α (THRA) or thyroid hormone receptor β (THRB) and can induce opposing impacts on health. On the one hand, people with hyperthyroidism accumulate liver damage and have shortened life spans. On the other hand, thyroid hormone receptor blocks cancer growth and metastasis.

Zambrano et al. discovered a possible explanation for this contradiction. They found that one thyroid hormone, T3, spurs cultured cells to senesce. T3 only triggered this effect through THRB, not THRA. Senescence didn’t require p53 but did require the DNA repair protein ATM.

T3 turned up mitochondrial activity, increasing production of noxious reactive oxygen species (ROS). This surge of ROS resulted in increased numbers of DNA double-strand breaks, thereby precipitating cellular senescence. Zambrano et al. also checked for the effect in young mice dosed with thyroid hormones for two weeks. Genetically altered mice lacking THRB showed little senescence, whereas wild-type animals carried a significant number of senescent cells in their livers.

Because senescent cells lose the ability to divide, the results suggest how activation of THRB can be both beneficial and detrimental. Although triggering senescence prevents damaged cells from becoming cancerous, it also might contribute to aging by curtailing the replacement of worn-out cells.


et al
J. Cell Biol.

Author notes

Text by Mitch Leslie