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Identifying the genes that yield the benefits of dietary restriction without the costs

Javier Gomez Ortega

School of Biological Sciences, Faculty of Sciences, Melbourne, Victoria, Australia

From dietary restriction [caloric restriction] to the manipulation of TOR (Target of Rapamycin) and insulin signalling, most anti-ageing strategies have shown side effects that make them inappropriate for translation to humans. This is thought to be due to the overlap between mechanisms affecting ageing and mechanisms associated with other physiological traits such as immunity, growth and fecundity. To solve this problem, we seek to separate anti-ageing processes from the associated costs. To do this, we study the effects of precise, single nutrient manipulations on fruit flies (Drosophila melanogaster). This approach reduces biological noise by simplifying the phenotypic changes associated with longevity. Specifically, we select nutrient manipulations that modify lifespan independently of fecundity. This makes it possible to differentiate between molecular changes that modulate lifespan, fecundity or both. Using these diets and transcriptomics, we adopt a systems biology approach to model the gene regulatory networks associated with lifespan and/or fecundity. I will present data from progress so far in a genetic screen to test modifiers of these gene networks in fruit flies.