Research

Thesis title: "Intestinal barrier dysfunction in ageing: Dissecting the underlying signalling cascades"

Thesis outline: The integrity of the intestinal barrier plays a critical role in maintaining human health. With
increasing age, the gut barrier becomes progressively compromised, contributing to systemic inflammation ("inflammaging") and age-related diseases. Lifestyle factors, especially diet, influence this decline. Notably, while high fructose intake has been associated with adverse effects on gut health in young individuals, preliminary data suggest that low fructose intake may actually improve gut barrier function and reduce cellular senescence in aged organisms.

This project aims to (1) investigate how low-dose fructose intake affects the ageing intestinal barrier in both humans and mice, and (2) elucidate the involvement of nitric oxide (NO) homeostasis and polyamine metabolism in modulating this process. By systematically investigating the complex interactions between fructose metabolism, NO signalling, and gut integrity in ageing, this study aims to identify novel dietary or
pharmacological strategies to maintain gut health in older individuals and mitigate age-associated decline.

Methodological Approach:

• Human Study: Randomized, blinded, crossover study investigating effects of acute and short-term fructose intake on intestinal permeability in healthy adults.
• Animal Studies: Long-term dietary interventions in aged C57BL/6 mice, as well as Arg2-knockout mice, to assess gut function and molecular markers.
• Ex vivo and in vitro Models: Use of everted gut sacs and CaCo-2 cells to analyze permeability, senescence induction, and involvement of NO and polyamine pathways (via specific inhibitors and activators).

Supervisor: Ina Bergheim

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