Medizinische Universität Graz - Research portal
Selected Publication:
Reiner, B.
The role of thyroid hormone T3 in modulating cellular signaling during senescence.
[ Diplomarbeit/Master Thesis (UNI) ] TU Graz; 2025. pp.47.
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- Authors Med Uni Graz:
- Advisor:
- Madreiter-Sokolowski Corina
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- Abstract:
- In our aging society, we experience a rise in aging-associated diseases and, thus, the necessity of understanding molecular mechanisms to develop novel anti-aging strategies. As one of the primary hallmarks of aging, cellular senescence represents a suitable starting point for intervening in the emergence of age-related diseases and enhancing longevity. Senescence is characterized by cellular hypertrophy and permanent cell cycle arrest while still being metabolically active. The key hubs of metabolism are mitochondria, the main place of intracellular ATP synthesis. The energy production is strongly influenced by Ca2+ homeostasis due to the Ca2+-dependence of dehydrogenases of the tricarboxylic acid cycle, which provide the electron donors for later ATP synthesis via oxidative phosphorylation. Thyroid hormones, especially the biologically active form 3,5,3'-L-triiodothyonine (T3), are known to be master regulators of cellular and organismal metabolism. Hence, we aimed to uncover the impact of T3 on the mitochondrial function in a cellular aging model based on oxidative stress-induced senescence. Therefore, we utilized tert-butyl hydroperoxide (tBHP)-treated fibroblasts to investigate the impact of T3 on expression levels of senescence- and mitochondrial Ca2+-related genes by qRT-PCR, performed fluorescence microscopy to measure mitochondrial ATP synthesis and cellular Ca2+ homeostasis, and checked senescence by the SA-β-galactosidase staining. We found that tBHP-induced senescence is linked to increased cytosolic Ca2+ levels, a drop in the mitochondrial membrane potential, and alterations in the mRNA expression levels of Ca2+ handling proteins and senescence markers. Notably, T3 treatment for 3 h showed a tendency to counteract most of these effects. Most prominently, increased p16ink4 expression found in tBHP-treated fibroblasts was normalized by T3. This result implies a potential involvement of T3 in the homeostasis of oxidative stress, which will be further investigated in follow-up studies.