Taste Perception Beyond Flavour: Bitter Taste Receptors in the Gastrointestinal Tract and Their Role in Ageing

Identifier:  TDX:4439

Handle: https://hdl.handle.net/20.500.11797/TDX4439

Authors:  Jalševac, Florijan

Abstract:
The population of the world is growing ever older, and with it, the incidence of age-associated disorders is on the rise. The constant internal and external stressors are balanced by homeostatic systems, which minimise their negative effects. Dysregulation of metabolic homeostasis is one of the main drivers of many age-accompanying disorders. Chemosensory receptors of the gastrointestinal tract (GIT) can be influenced to elicit several beneficial effects. One group of these receptors are the bitter taste receptors (TAS2R). TAS2R and their ligands, such as grape seed proanthocyanidin extract (GSPE) have been proposed as novel ways to achieve healthier ageing. In this dissertation, we discuss the diversity in the TAS2R throughout GIT, their evolution with ageing, and focus on establishing which out of 26 human receptors are more likely to have a role in the progress of ageing. Additionally, we focus on how GSPE and its constituents influence the changes in the presence of TAS2R in the GIT, and how they influence the secretory potential of the GIT. We discovered that some receptors are more present in specific segments of the GIT, and interestingly, the ageing upregulated the expression of a handful of TAS2Rs in the colon mucosa. TAS2R5 was labelled as the most probable receptor to have important roles in the progress of ageing, due to its correlations with several parameters that are known to impact overall health. Finally, GSPE has proven to be a potent regulator of TAS2R expression, and its constituent epicatechin has been shown to impact the secretory role of the GIT cells. In summary, this thesis presents TAS2R as interesting novel targets for potentially impacting the progress of ageing, due to their involvement in the centre of metabolic regulation and possible activation with bioactive compounds, which could elicit multiple beneficial effects.