Catalyst Awardee

Project Description

The mechanisms of lifespan regulation by dietary manipulation

Obata Fumiaki, PhD

Competition Sponsor: Japan Agency for Medical Research and Development

Almost all animals, including humans, develop into adults and eventually age over time. As an environmental factor, dietary intake is essential throughout life. Diet contributes to metabolic and physiological homeostasis via nutrition, the composition of which is modulated by gut microbiota. Although the significance of dietary quality is well recognised, how each nutrient in diet and each bacterium in the gut influence the healthspan are poorly understood at a molecular level. This study utilises the short lifecycle and abundant genetic tools of fruit fly Drosophila melanogaster to understand how diet impacts organismal homeostasis and lifespan. We take advantage of an established chemically-defined diet. This synthetic medium is composed of approximately 40 compounds, which allows us to restrict a single nutrient to perform “loss of function” experiment. In particular, we focus on how each amino acid or mineral plays a role in lifespan determination. At the same time, the gnotobiotic experiment, by which we can produce flies with defined gut microbial composition, is readily accessible. We will elucidate the molecular mechanism of nutritional and microbial regulation of the host healthspan by multi-omics analysis and genetic dissection of responsible molecular pathways. We also aim to elucidate the mechanism underlying the prolonged effect of early-life diet on adult physiology. Our study would provide basic knowledge of evolutionally-conserved molecular mechanisms of dietary regulation of organismal longevity. This should help create an effective dietary intervention to extend the human healthspan by targeting people in all life stages.

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