Medizinische Universität Graz - Research portal
Selected Publication:
Pfennich, PS.
The role of triiodothyronine in modulating mitochondrial signaling during aging.
[ Diplomarbeit/Master Thesis (UNI) ] Universität Graz; 2025. pp.47.
FullText
- Authors Med Uni Graz:
- Advisor:
- Madreiter-Sokolowski Corina
- Altmetrics:
- Abstract:
- Aging is a complex biological process characterized by a decline in cellular function and metabolic efficiency. Mitochondria, the powerhouses of the cell and initiators of programmed cell death, play a crucial role in energy production and the aging process. Thyroid hormones, key regulators of metabolism, profoundly impact mitochondrial function. Our previous work demonstrated that the biologically active triiodothyronine (T3) enhances mitochondrial metabolism in cancer cells by upregulating mitochondrial calcium (Ca2+) handling proteins, which in turn boost the activity of tricarboxylic adic cycle dehydrogenases and overall mitochondrial metabolism. Given that subclinical hypothyroidism is associated with slower metabolism, reduced oxidative stress, and prolonged lifespan, we hypothesize that T3 induces mitochondrial-specific signaling cascades during aging. To test this hypothesis, we induced premature senescence in HFF-1 fibroblasts using tert-butyl hydroperoxide (tBHP) and utilized this cellular aging model to investigate the impact of T3 on young and senescent cells. We measured mitochondrial nicotinamide adenine dinucleotide (NADH) index, mitochondrial Ca2+, and adenosine triphosphate (ATP) homeostasis, as well as cytosolic and mitochondrial reactive oxygen species (ROS) levels using organelle-targeted biosensors. Additionally, we analyzed the expression levels of genes related to senescence, oxidative stress defense, and mitochondrial Ca2+ handling via quantitative real-time PCR. We found that oxidative-stress induced senescence increases the colocalisation between mitochondria and the endoplasmic reticulum, boosts stress in the endoplasmic reticulum, and increases cytosolic Ca2+ and ROS levels. Interestingly, T3 seems to counteract these observed changes. These results might help to further characterize mechanisms of T3-induced signaling cascades that modulate lifespan and health span, identifying critical targets for novel anti-aging strategies.