Investigating the effects of Natural and Synthetic Compounds on the health and ageing of the model organism C. elegans

The global population is ageing rapidly, with the developing countries of Asia and the Western world’s economies and healthcare systems projected to bear the biggest burden of the ageing demographics. One potential solution could lie in the age-old wisdom of traditional medicine, which has been practised for millennia and is still widely accepted and popular. Herbs, spices and other sources have been known for their health benefits, albeit research on their biologically active compounds and mechanisms of action is limited. In this research, I tested a range of natural compounds found in popular sources of traditional Asian medicine and Western diet to uncover their potential health benefits on the model organism C. elegans. In addition, I tested a novel class of synthetic compounds, the Supramolecular Self-Associating Amphiphiles (SSAs), known for their cytotoxic effects and chemotherapy-enhancing potential. This research showed that a group of natural compounds is activating HSP-4, a core component of the ER UPR, which translates into resistance to acute proteostatic stress. Furthermore, it is shown that one of the compounds, Crinamine, has differential effects on the nematode’s development, fertility and resistance to the proteotoxic agent Tunicamycin, depending on the exposure duration. Crinamine is also shown to reduce amyloid-induced paralysis in an Alzheimer’s disease nematode strain, without affecting total amyloid aggregation, while Crinamine and Isosteviol are shown to increase poly-glutamine-induced Paralysis and poly-glutamine aggregation in a Huntington’s Disease nematode strain. Lastly, this research shows that the SSAs are consumed and interact with the nematode’s intestinal lumen, without affecting its development and fertility. This research highlights the potential of natural compounds found in everyday diet sources as therapeutic agents, mediating protein regulation and interaction pathways and the potential of the SSAs as cytotoxic agents which do not affect a host multicellular organism, while killing cancer and bacterial cells.