The diet an organism keeps is crucial in sustaining its health and fitness. The fruit fly Drosophila melanogaster and the nematode Caenorhabditis elegans are excellent models for nutritional studies due to their small size, large progeny numbers, quick development, and modifiable laboratory diets. Here I examine these two organisms in order to better understand the complex interrelationship between an animal and its diet. Previous work has shown that in the wild numerous organisms are capable of selecting specific nutrients in a non-random manner in order to maximize fitness. However, the genetic underpinnings driving these nutrient choices remain elusive. Female fruit flies consume higher levels of protein following mating to prepare for the costs of reproduction. I examined the role of S6 Kinase (S6K), a downstream effector of the nutrient-responsive target of rapamycin pathway, in mediating this decision. I demonstrate that neuronal S6K activity and serotonin are involved in regulating protein consumption when allowed to choose nutrients freely as well as following macronutrient deprivation; suggesting that they may play a role in mediating postmating dietary switch and maintaining nutrient balance. Modulating levels of dietary components can have extensive impacts on processes such as development, fecundity, and metabolism in multiple organisms. However, the influence of dietary genetics on the consumer is virtually unknown. I performed a screen feeding single-gene mutants of E. coli to C. elegans and monitored the effects on the insulin-like signalling pathway (ILS). When mutated, genes involved in multiple processes and functions in E. coli enhanced activity of the ILS downstream transcription factor, DAF-16. One mutant strain of E. coli I pursued had a knockout of the cAMP-producing, adenylate cyclase gene. Addition of exogenous cAMP to the diet containing live, metabolically active E. coli rescued all the effects of the mutant on C. elegans; thereby suggesting that bacterial metabolism of dietary cAMP can influence the C. elegans ILS. Collectively, my work demonstrates how the nutrient-sensing pathways of the consumer can shape and be shaped by interactions with its diet. These studies contribute to a better understanding of the consumer-diet relationship, and could help guide future work to investigate the role of diet in disease, quality of life, and longevity.

Ageing is a progressive impairment of function causing decreased defense against environmental challenges and increased risk of many diseases. The development of ageing and ageing-related diseases might be attenuated by nutrients such as carotenoids and polyunsaturated fatty acids. In the present study, for the first time, two nutrient-rich marine microalgae, namely Haematococcus pluvialis (HP) and Schizochytrium mangrovei (SM) were studied for their anti-ageing effects both in vitro and in vivo. Results of nutritional profile analysis confirmed that HP is rich in astaxanthin (AX) (978.9 μg/g). Using rat adrenal medulla pheochromocytoma (PC12) cells as an in vitro model, AX exhibited significant protective effects against oxidative stress induced by H2O2 or amyloid β-peptide (Aβ). To testify whether AX conveys such effects to HP, the anti-ageing property of HP was subsequently investigated on Drosophila melanogaster. In the group of SODn108 mutant fruit flies, lifespan elongation effect was observed, where HP may play as a complement of the defective endogenous antioxidant system to extend the lifespan and ameliorate the age-related decline of locomotor function. On the other hand, a long-term intake of HP (20 mg/mL) induced early mortality of wild type fruit flies, which was associated with the decreased enzymatic activities of CuZn-superoxide dismutase (SOD1) and Mn-superoxide dismutase (SOD2) as well as mRNA down-regulation of SOD1, SOD2, and Catalase (CAT). Further study showed that HP supplementation contributed to the defense of wild type OR fruit flies against chronic but not intensive oxidative stress. The observed ‘bifacial effect’ could be resulted from ‘hormesis’ responses, suggesting the therapeutic instead of the preventive potential of HP against ageing-related diseases. Another microalga SM was found to contain abundant docosahexaenoic acid (DHA) (53 mg/g). The in vitro studies showed that SM failed to protect PC12 cells under H2O2-induced oxidative stress due to its poor anti-oxidative activity. However, from in vivo studies, the SM supplementation significantly extended the lifespan of both wild type and SODn108 mutant fruit flies and ameliorated the age-related decline of locomotor function. Further studies revealed that the observed activities were associated with the mRNA up-regulation of endogenous stress-defending genes such as SOD1 and SOD2, as well as the down-regulation of methuselah (MTH) gene. It has been proposed that antioxidants may protect DHA against oxidative damage. To determine whether there is a synergistic effect for HP and SM, a mixture of these two algal samples was evaluated for its effects on the lifespan of D. melanogaster. Results showed that the wild type fruit flies fed with the mixture had no elevated survival rate, tentatively suggesting that the increased nutritional complexity may trigger elevated metabolic rate and lead to shortened lifespan. In conclusion, results of the present study demonstrated the anti-ageing properties of nutrient-rich microalgae both in vitro and in vivo, suggesting SM possesses the potential to be used as a preventive diet supplementation, while HP may be a suitable candidate as therapeutic agents. Based on these findings, the health benefits of nutrient-rich microalgae for the elderly as well as patients with ageing-related diseases were proposed. / published_or_final_version / Biological Sciences / Doctoral / Doctor of Philosophy

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