The thyroid hormone receptor β induces DNA damage and premature senescence

摘要: There is increasing evidence that the thyroid hormone (TH) receptors (THRs) can play a role in aging, cancer and degenerative diseases. In this paper, we demonstrate binding of TH T3 (triiodothyronine) to THRB induces senescence deoxyribonucleic acid (DNA) damage cultured cells tissues young hyperthyroid mice. rapid activation ATM (ataxia telangiectasia mutated)/PRKAA (adenosine monophosphate–activated protein kinase) signal transduction recruitment NRF1 (nuclear respiratory factor 1) promoters genes with key on mitochondrial respiration. Increased respiration leads production reactive oxygen species, which turn causes oxidative stress DNA double-strand breaks triggers response ultimately premature susceptible cells. Our findings provide mechanism for integrating metabolic effects THs tumor suppressor activity THRB, effect thyroidal status longevity, occurrence tissue hyperthyroidism.