Age-associated increase of thyroid hormone receptor β gene promoter methylation coexists with decreased gene expression

ABSTRACTPurpose: It is not established if healthy aging of the thyroid axis is associated with alterations other than changes in hormone secretion.Methods: The expression of thyroid hormone receptor β gene (THRB) was analyzed in peripheral blood mononuclear cells (PBMC) obtained from young, elderly, and long-lived individuals. The interaction between the 3ʹUTR of TRβ1 mRNA and selected miRNAs was measured using pmirGLO reporter vector. Methylation of the THRB CpG island was analyzed using methylation-sensitive restriction/RT-PCR and bisulfite sequencing methods.Results: Old age was associated with a significantly lower amount of total TRβ mRNA (p = 0.033) and of TRβ1 mRNA (p = 0.02). Older age was also associated with significantly higher methylation of the THRB promoter (restriction/RT-PCR: p = 0.0023, bisulfite sequencing: p = 0.0004). Higher methylation corresponded to a lower expression of the THRB mRNA, but this correlation did not reach the level of significance. miR-26a interacted with two sites in...