Tissue-Specific Suppression of Thyroid Hormone Signaling in Various Mouse Models of Aging.

Autor: Visser WE; Dept of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands., Bombardieri CR; MGC Dept of Genetics, Cancer Genomics Center, Erasmus Medical Center, Rotterdam, The Netherlands., Zevenbergen C; Dept of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands., Barnhoorn S; MGC Dept of Genetics, Cancer Genomics Center, Erasmus Medical Center, Rotterdam, The Netherlands., Ottaviani A; MGC Dept of Genetics, Cancer Genomics Center, Erasmus Medical Center, Rotterdam, The Netherlands.; Institute for Research on Cancer and Aging, Nice (IRCAN), UMR 7284 CNRS U1081 INSERM UNS, 28 avenue de Valombrose Faculté de Médecine, Nice, France., van der Pluijm I; MGC Dept of Genetics, Cancer Genomics Center, Erasmus Medical Center, Rotterdam, The Netherlands., Brandt R; MGC Dept of Genetics, Cancer Genomics Center, Erasmus Medical Center, Rotterdam, The Netherlands., Kaptein E; Dept of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands., van Heerebeek R; Dept of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands., van Toor H; Dept of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands., Garinis GA; MGC Dept of Genetics, Cancer Genomics Center, Erasmus Medical Center, Rotterdam, The Netherlands., Peeters RP; Dept of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands., Medici M; Dept of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands., van Ham W; Laboratory of Comparative Endocrinology, Biology Department, KULeuven, Leuven, Belgium., Vermeij WP; MGC Dept of Genetics, Cancer Genomics Center, Erasmus Medical Center, Rotterdam, The Netherlands., de Waard MC; MGC Dept of Genetics, Cancer Genomics Center, Erasmus Medical Center, Rotterdam, The Netherlands., de Krijger RR; Dept of Pathology, Erasmus Medical Center, Rotterdam, The Netherlands., Boelen A; Dept of Endocrinology and Metabolism, Academic Medical Center, Amsterdam, The Netherlands., Kwakkel J; Dept of Endocrinology and Metabolism, Academic Medical Center, Amsterdam, The Netherlands., Kopchick JJ; Dept of Biomedical Sciences, Edison Biotechnology Institute, Ohio University, Athens, Ohio, United States of America., List EO; Dept of Biomedical Sciences, Edison Biotechnology Institute, Ohio University, Athens, Ohio, United States of America., Melis JP; Dept of Toxicogenetics, Leiden University Medical Center, Leiden, The Netherlands., Darras VM; Laboratory of Comparative Endocrinology, Biology Department, KULeuven, Leuven, Belgium., Dollé ME; Centre for Health Protection Research, National Institute of Public Health and the Environment (RIVM), Bilthoven, The Netherlands., van der Horst GT; MGC Dept of Genetics, Cancer Genomics Center, Erasmus Medical Center, Rotterdam, The Netherlands., Hoeijmakers JH; MGC Dept of Genetics, Cancer Genomics Center, Erasmus Medical Center, Rotterdam, The Netherlands., Visser TJ; Dept of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2016 Mar 08; Vol. 11 (3), pp. e0149941. Date of Electronic Publication: 2016 Mar 08 (Print Publication: 2016).
DOI: 10.1371/journal.pone.0149941
Abstrakt: DNA damage contributes to the process of aging, as underscored by premature aging syndromes caused by defective DNA repair. Thyroid state changes during aging, but underlying mechanisms remain elusive. Since thyroid hormone (TH) is a key regulator of metabolism, changes in TH signaling have widespread effects. Here, we reveal a significant common transcriptomic signature in livers from hypothyroid mice, DNA repair-deficient mice with severe (Csbm/m/Xpa-/-) or intermediate (Ercc1-/Δ-7) progeria and naturally aged mice. A strong induction of TH-inactivating deiodinase D3 and decrease of TH-activating D1 activities are observed in Csbm/m/Xpa-/- livers. Similar findings are noticed in Ercc1-/Δ-7, in naturally aged animals and in wild-type mice exposed to a chronic subtoxic dose of DNA-damaging agents. In contrast, TH signaling in muscle, heart and brain appears unaltered. These data show a strong suppression of TH signaling in specific peripheral organs in premature and normal aging, probably lowering metabolism, while other tissues appear to preserve metabolism. D3-mediated TH inactivation is unexpected, given its expression mainly in fetal tissues. Our studies highlight the importance of DNA damage as the underlying mechanism of changes in thyroid state. Tissue-specific regulation of deiodinase activities, ensuring diminished TH signaling, may contribute importantly to the protective metabolic response in aging.
Databáze: MEDLINE