Organisms from slime moulds to humans carefully regulate their macronutrient intake to optimize a wide range of life history characters including survival, stress resistance, and reproductive success. However, life history characters often differ in their response to nutrition, forcing organisms to make foraging decisions while balancing the trade-offs between these effects. To date, we have a limited understanding of how the nutritional environment shapes the relationship between life history characters and foraging decisions. To gain insight into the problem, we used a geometric framework for nutrition to assess how the protein and carbohydrate content of the larval diet affected key life history traits in the fruit fly, Drosophila melanogaster. In no-choice assays, survival from egg to pupae, female and male body size, and ovariole number - a proxy for female fecundity - were maximized at the highest protein to carbohydrate (P:C) ratio (1.5:1). In contrast, development time was minimized at intermediate P:C ratios, around 1:2. Next, we subjected larvae to two-choice tests to determine how they regulated their protein and carbohydrate intake in relation to these life history traits. Our results show that larvae targeted their consumption to P:C ratios that minimized development time. Finally, we examined whether adult females also chose to lay their eggs in the P:C ratios that minimized developmental time. Using a three-choice assay, we found that adult females preferentially laid their eggs in food P:C ratios that were suboptimal for all larval life history traits. Our results demonstrate that D. melanogaster larvae make foraging decisions that trade-off developmental time with body size, ovariole number, and survival. In addition, adult females make oviposition decisions that do not appear to benefit the larvae. We propose that these decisions may reflect the living nature of the larval nutritional environment in rotting fruit. These studies illustrate the interaction between the nutritional environment, life history traits, and foraging choices in D. melanogaster, and lend insight into the ecology of their foraging decisions.

Despite their fundamental importance for body size regulation, the mechanisms that stop growth are poorly understood. In Drosophila melanogaster, growth ceases in response to a peak of the molting hormone ecdysone that coincides with a nutrition-dependent checkpoint, critical weight. Previous studies indicate that insulin/insulin-like growth factor signaling (IIS)/Target of Rapamycin (TOR) signaling in the prothoracic glands (PGs) regulates ecdysone biosynthesis and critical weight. Here we elucidate a mechanism through which this occurs. We show that Forkhead Box class O (FoxO), a negative regulator of IIS/TOR, directly interacts with Ultraspiracle (Usp), part of the ecdysone receptor. While overexpressing FoxO in the PGs delays ecdysone biosynthesis and critical weight, disrupting FoxO–Usp binding reduces these delays. Further, feeding ecdysone to larvae eliminates the effects of critical weight. Thus, nutrition controls ecdysone biosynthesis partially via FoxO–Usp prior to critical weight, ensuring that growth only stops once larvae have achieved a target nutritional status.DOI: http://dx.doi.org/10.7554/eLife.03091.001

In most animals reproduction trades off with somatic maintenance and survival. Physiologically this trade-off is mediated by hormones with opposite effects on reproduction and maintenance. In many insects, this regulation is achieved by an endocrine network that integrates insulin-like/IGF-1 signaling (IIS), juvenile hormone (JH), and the yolk precursor vitellogenin (Vg) (or, more generally, yolk proteins [YPs]). Downregulation of this network promotes maintenance and survival at the expense of reproduction. Remarkably, however, queens of highly eusocial social insects exhibit both enormous reproductive output and longevity, thus escaping the trade-off. Here we argue - based on recent evidence - that the proximate reason for why eusocial insects can decouple this trade-off is that they have evolved a different 'wiring' of the IIS-JH-Vg/YP circuit.

1Manipulating amino acid (AA) intake in Drosophila can profoundly affect lifespan and reproduction. Remarkably, AA manipulation can uncouple the commonly observed trade-off between these traits. This finding seems to challenge the idea that this trade-off is due to competitive resource allocation, but here we argue that this view might be too simplistic. We also discuss the mechanisms of the AA response, mediated by the IIS/TOR and GCN2 pathways. Elucidating how these pathways respond to specific AA will likely yield important insights into how AA modulate the reproduction-lifespan relationship. The Drosophila model offers powerful genetic tools, combined with options for precise diet manipulation, to address these fundamental questions. Introduction: dietary effects on lifespan and reproductionNutrition plays a primary role in shaping the physiology, life history and behavior of organisms, and nutritional interventions can have substantial health benefits [1]. Dietary restriction (DR), that is, the reduced intake of nutrients without malnutrition, has been the most widely studied nutritional intervention since the 1930s when it was first demonstrated that DR extends lifespan in rats. Since then, a large body of research has established positive effects of DR on longevity and age-related pathology in numerous organisms, ranging from yeast and worms to insects and mammals. At the same time, DR typically reduces reproductive output [2,3]. The fact that reduced food intake extends lifespan at the expense of reproduction makes the study of DR, and of dietary effects more generally, of key significance for our understanding of the commonly observed trade-off between reproduction and longevity [4,5].Originally, reduced intake of calories was thought to be responsible for the lifespan-extending effects of DR, but this view began to shift when studies in Drosophila showed that lifespan extension under DR does not depend on caloric restriction [5,6]. By testing diets with different nutrient compositions ('nutritional geometry framework') [7], it was found that the ratio of proteins to carbohydrates (P:C ratio), not overall energetic content, affects lifespan and reproduction in Drosophila [8,9]. Today, there is growing evidence that especially dietary proteins play a major role in mediating the effects of DR [10,11] (but see [12]). Remarkably, beyond the effects of the proteins themselves, recent work suggests that the building blocks of proteins, that is, specific amino acids (AA), can profoundly impact lifespan and associated traits. For example, in both flies and mice, restriction of dietary methionine can extend lifespan to the same extent as DR [13][14][15][16].Here, we give a brief review of how AA modulate lifespan and reproduction, and the trade-off between these traits. We also provide a short overview of the molecular mechanisms by which AA might control these two traits and their relationship. We focus on recent research in the Drosophila model, given that this system combines unrivaled genetic tools, a solid...

Evolutionary theories of ageing predict a reduction in selection efficiency with age, a so-called ‘selection shadow’, due to extrinsic mortality decreasing effective population size with age. Classic symptoms of ageing include a deterioration in transcriptional regulation and protein homeostasis. Understanding how ant queens defy the trade-off between fecundity and lifespan remains a major challenge for the evolutionary theory of ageing. It has often been discussed that the low extrinsic mortality of ant queens, that are generally well protected within the nest by workers and soldiers, should reduce the selection shadow acting on old queens. We tested this by comparing strength of selection acting on genes upregulated in young and old queens of the ant, Cardiocondyla obscurior. In support of a reduced selection shadow, we find old-biased genes to be under strong purifying selection. We also analysed a gene co-expression network (GCN) with the aim to detect signs of ageing in the form of deteriorating regulation and proteostasis. We find no evidence for ageing. In fact, we detect higher connectivity in old queens indicating increased transcriptional regulation with age. Within the GCN, we discover five highly correlated modules that are upregulated with age. These old-biased modules regulate several anti-ageing mechanisms such as maintenance of proteostasis, transcriptional regulation and stress response. We observe stronger purifying selection on central hub genes of these old-biased modules compared to young-biased modules. These results indicate a lack of transcriptional ageing in old C. obscurior queens possibly facilitated by strong selection at old age and well-regulated anti-ageing mechanisms.

Life-history theory posits that investment into reproduction might occur at the expense of investment into somatic maintenance, including immune function. If so, reduced or curtailed reproductive effort might be expected to increase immunity. In support of this notion, work in Caenorhabditis elegans has shown that worms lacking a germline exhibit improved immunity, but whether the antagonistic relation between germline proliferation and immunity also holds for other organisms is less well understood. Here, we report that transgenic ablation of germ cells in late development or early adulthood in Drosophila melanogaster causes elevated baseline expression and increased induction of Toll and Imd immune genes upon bacterial infection, as compared to fertile flieswith an intact germline. We also identify immune genes whose expression after infection differs between fertile and germline-less flies in a manner that is conditional on their mating status. We conclude that germline activity strongly impedes the expression and inducibility of immune genes and that this physiological trade-off might be evolutionarily conserved.

Evolutionary theories of ageing predict a reduction in selection efficiency with age, a so-called 'selection shadow', due to extrinsic mortality decreasing effective population size with age. Classic symptoms of ageing include a deterioration in transcriptional regulation and protein homeostasis. Understanding how ant queens defy the trade-off between fecundity and lifespan remains a major challenge for the evolutionary theory of ageing. It has often been discussed that the low extrinsic mortality of ant queens, that are generally well protected within the nest by workers and soldiers, should reduce the selection shadow acting on old queens. We tested this by comparing strength of selection acting on genes upregulated in young and old queens of the ant, Cardiocondyla obscurior. In support of a reduced selection shadow, we find old-biased genes to be under strong purifying selection. We also analysed a gene co-expression network (GCN) with the aim to detect signs of ageing in the form of deteriorating regulation and proteostasis. We find no evidence for ageing. In fact, we detect higher connectivity in old queens indicating increased transcriptional regulation with age. Within the GCN, we discover five highly correlated modules that are upregulated with age. These old-biased modules regulate several anti-ageing mechanisms such as maintenance of proteostasis, transcriptional regulation and stress response. We observe stronger purifying selection on central hub genes of these old-biased modules compared to young-biased modules. These results indicate a lack of transcriptional ageing in old C. obscurior queens possibly facilitated by strong selection at old age and well-regulated anti-ageing mechanisms.

Despite their fundamental importance for body size regulation, the mechanisms that stop growth are poorly understood. In Drosophila melanogaster, growth ceases in response to a peak of the molting hormone ecdysone that coincides with a nutrition-dependent checkpoint, critical weight. Previous studies indicate that insulin/insulin-like growth factor signaling (IIS)/Target of Rapamycin (TOR) signaling in the prothoracic glands (PGs) regulates ecdysone biosynthesis and critical weight. Here we elucidate a mechanism through which this occurs. We show that Forkhead Box class O (FoxO), a negative regulator of IIS/TOR, directly interacts with Ultraspiracle (Usp), part of the ecdysone receptor. While overexpressing FoxO in the PGs delays ecdysone biosynthesis and critical weight, disrupting FoxO-Usp binding reduces these delays. Further, feeding ecdysone to larvae eliminates the effects of critical weight. Thus, nutrition controls ecdysone biosynthesis partially via FoxO-Usp prior to critical weight, ensuring that growth only stops once larvae have achieved a target nutritional status.