ECE2014 Poster Presentations Thyroid (non-cancer) (125 abstracts)
1Department of Human Epigenetics, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland; 2Department of Geriatrics and Gerontology, Medical Center of Postgraduate Education, Warsaw, Poland.
Introduction: Decreased function of the thyroid axis during aging is associated with a better functional performance and longer survival. This phenomenon can be a result not only of a lower production of thyroid hormones including bioavailable triiodothyronine, but also of age-associated alterations regarding triiodothyronine receptors.
Methods: Functional studies regarding interaction between the 3′UTR of TRβ1 mRNA and in silico-identified miRNAs (miR-26a and miR-496) that potentially interact with this mRNA, were performed in HEK293 cells. Analysis of the expression of THRB and abovementioned miRNAs was performed in peripheral blood mononuclear cells (PBMCs) of young (Y, n=53, 1842 years), elderly (E, n=50, 6075 years), and long-lived (L, n=51, >90 years) individuals using Q8 real-time PCR. Statistical analysis was performed using Students t-test, KruskalWallis test, and Spearmans rank correlation coefficient.
Results: Functional studies showed that miR-26a interacted with two sites located within the 3′UTR of TRβ1 mRNA and that such interaction resulted in the reduction of activity of the reporter protein by 31 and 23.5%, (P<0.0001 and P=0.0005 respectively). miR-496 interacted with one of the two putative binding sites within the tested 3′UTR and reduced the activity of the reporter protein by 42.3% (P<0.0001).The median expression of THRB was significantly lower in the long-lived than in young group (P=0.03). In addition, the median expression of miR-26a was also significantly lower in the long-lived than in young group (P=0.032), while the expression of miR-496 was not affected by age in PBMCs. There was no correlation between the expression of THRB and of both miRNAs.
Conclusion: Age-related decrease of the expression of THRB in human PBMCs is independent of both miR-26a and miR-496.