A dietary sterol trade-off determines lifespan responses to dietary restriction in Drosophila melanogaster females.

Diet plays a significant role in maintaining lifelong health. In particular, lowering the dietary protein: carbohydrate ratio can improve lifespan. This has been interpreted as a direct effect of these macronutrients on physiology. Using Drosophila melanogaster, we show that the role of protein and carbohydrate on lifespan is indirect, acting by altering the partitioning of limiting amounts of dietary sterols between reproduction and lifespan. Shorter lifespans in flies fed on high protein: carbohydrate diets can be rescued by supplementing their food with cholesterol. Not only does this fundamentally alter the way we interpret the mechanisms of lifespan extension by dietary restriction, these data highlight the important principle that life histories can be affected by nutrient-dependent trade-offs that are indirect and independent of the nutrients (often macronutrients) that are the focus of study. This brings us closer to understanding the mechanistic basis of dietary restriction.

For the past fifteen years, animal studies have consistently shown that a low-protein, high-carbohydrate ('carbs') diet can extend the lifespan of many organisms, but at the cost of the number of offspring an individual can produce. Yet, it is still unclear what the best dietary balance is, and how these effects arise. One potential explanation could be that reproduction damages the body: low levels of proteins would therefore prolong life by lowering the reproductive output. Here, Zanco et al. examined the possibility that protein intake in fruit flies could instead be acting indirectly by changing the levels of a fat-like molecule called cholesterol, which is used to maintain the body and to support reproduction. To test this idea, groups of fruit flies were fed high levels of proteins. This led to increased reproduction rates, in turn depleting the mothers' reserves of cholesterol. Without enough of the molecule in their diet, the insects were less able to maintain their bodies, which reduced their lifespan. When Zanco et al. added cholesterol to a high-protein diet, the flies lived for the normal length of time. Longer lifespan therefore did not require restriction of the diet or any of its components. In fact, the flies that lived the longest ate protein rich diets, and reproduced the most. This study helps to better understand why changes in diet can influence how long an organism lives for, highlighting that the abundance of certain key molecules may be more important than restricting the levels of proteins, carbs or calories actually consumed.

Sex-specific transcriptomic responses to changes in the nutritional environment.

Males and females typically pursue divergent reproductive strategies and accordingly require different dietary compositions to maximise their fitness. Here we move from identifying sex-specific optimal diets to understanding the molecular mechanisms that underlie male and female responses to dietary variation in Drosophila melanogaster. We examine male and female gene expression on male-optimal (carbohydrate-rich) and female-optimal (protein-rich) diets. We find that the sexes share a large core of metabolic genes that are concordantly regulated in response to dietary composition. However, we also observe smaller sets of genes with divergent and opposing regulation, most notably in reproductive genes which are over-expressed on each sex's optimal diet. Our results suggest that nutrient sensing output emanating from a shared metabolic machinery are reversed in males and females, leading to opposing diet-dependent regulation of reproduction in males and females. Further analysis and experiments suggest that this reverse regulation occurs within the IIS/TOR network.

Turning food into eggs: insights from nutritional biology and developmental physiology of Drosophila.

Nutrition plays a central role in fecundity, regulating the onset of reproductive maturity, egg production, and the survival and health of offspring from insects to humans. Although decades of research have worked to uncover how nutrition mediates these effects, it has proven difficult to disentangle the relative role of nutrients as the raw material for egg and offspring development versus their role in stimulating endocrine cascades necessary to drive development. This has been further complicated by the fact that both nutrients and the signalling cascades they regulate interact in complex ways to control fecundity. Separating the two effects becomes important when trying to understand how fecundity is regulated, and in devising strategies to offset the negative effects of nutrition on reproductive health. In this review, we use the extensive literature on egg development in the fruit fly Drosophila melanogaster to explore how the nutrients from food provide the building blocks and stimulate signalling cascades necessary for making an egg.

Using artificial diets to understand the nutritional physiology of Drosophila melanogaster.

Artificial diets have been in use for rearing insects for more than 100 years. Their composition ranges from completely chemically defined (holidic), to semi-defined (meridic) to non-defined (oligidic). Recently, meridic and holidic diets have been used to demonstrate previously unrecognised nutrient-sensitive behaviours and patterns of fitness trait expression in adult Drosophila melanogaster. This article presents a summary of the basic nutritional requirements of Drosophila followed by an account of some of these nutrient-modified phenotypes and what they can reveal about fundamental mechanisms. Precisely controlled nutrition, combined with the many advantages of Drosophila present an ideal system for the development of large scale metabolic modelling.

Matching complex dietary landscapes with the signalling pathways that regulate life history traits.

The rise in obesity in human populations has reinvigorated research focused on how nutrition impacts life history traits, including body size, lifespan, reproductive success, stress resistance and propensity for disease. Studies have ranged in their approach from identifying the molecular machinery responding to changes in nutrient levels, to understanding the hormonal changes that occur in response to diet, to mapping the response of differing life history traits over complex dietary landscapes. Connecting insights across these approaches presents significant challenges primarily because we lack information about how signalling pathways respond to dietary complexity. Here, we offer our perspective on how to integrate insights from the cellular to the whole organism to understand the regulation of life history traits.