Dietary restriction (DR) extends life span in many organisms, through unknown mechanisms that may or may not be evolutionarily conserved. Because different laboratories use different diets and techniques for implementing DR, the outcomes may not be strictly comparable. This complicates intra- and interspecific comparisons of the mechanisms of DR and is therefore central to the use of model organisms to research this topic. Drosophila melanogaster is an important model for the study of DR, but the nutritional content of its diet is typically poorly defined. We have compared fly diets composed of different yeasts for their effect on life span and fecundity. We found that only one diet was appropriate for DR experiments, indicating that much of the published work on fly "DR" may have included adverse effects of food composition. We propose procedures to ensure that diets are suitable for the study of DR in Drosophila.

One-carbon metabolism in yeast is an essential process that relies on at least one of three one-carbon donor molecules: serine, glycine, or formate. By a combination of genetics and biochemistry we have shown how cells regulate the balance of one-carbon flow between the donors by regulating cytoplasmic serine hydroxymethyltransferase activity in a side reaction occurring in the presence of excess glycine. This control governs the level of 5,10-methylene tetrahydrofolate (5,10-CH 2 -H 4 folate) in the cytoplasm, which has a direct role in signaling transcriptional control of the expression of key genes, particularly those encoding the unique components of the glycine decarboxylase complex (GCV1, GCV2, and GCV3). Based on these and other observations, we propose a model for how cells balance the need to supplement their one-carbon pools when charged folates are limiting or when glycine is in excess. We also propose that under normal conditions, cytoplasmic 5,10-CH 2 -H 4 folate is mainly directed to generating methyl groups via methionine, whereas one-carbon units generated from glycine in mitochondria are more directed to purine biosynthesis. When glycine is in excess, 5,10-CH 2 -H 4 folate is decreased, and the regulation loop shifts the balance of generation of one-carbon units into the mitochondrion.

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Reduction of food intake without malnourishment extends life span in many different organisms. The majority of work in this field has been performed in rodents where it has been shown that both restricting access to the entire diet and restricting individual dietary components can cause life-span extension. Thus, for insights into the mode of action of this intervention, it is of great interest to investigate the aspects of diet that are critical for life span extension. Further studies on the mechanisms of how food components modify life span are well suited to the model organism Drosophila melanogaster because of its short life span and ease of handling and containment. Therefore, we summarize practical aspects of implementing dietary restriction in this organism, as well as highlight the major advances already made. Delineation of the nutritional components that are critical for life-span extension will help to reveal the mechanisms by which it operates.

AbstractDiet composition, especially the relative abundance of key macronutrients, is well known to affect animal wellbeing by changing reproductive output, metabolism and length of life. However, less attention has been paid to the ways the quality of these nutrients modify these macronutrient interactions. Nutritional Geometry can be used to model the effects of multiple dietary components on life-history traits and to compare these responses when diet quality is varied. Previous studies have shown that dietary protein quality can be increased for egg production in Drosophila melanogaster by matching the dietary amino acid proportions to the balance of amino acids used by the sum of proteins in the fly’s in silico translated exome. Here, we show that dietary protein quality dramatically alters the effect of protein quantity on female reproduction across a broad range of diets varying in both protein and carbohydrate concentrations. These data show that when sources of ingredients vary, their relative value to the consumer can vastly differ and yield very different physiological outcomes. Such variations could be particularly important for meta analyses that look to draw generalisable conclusions from diverse studies.

23Males and females typically pursue divergent reproductive strategies and accordingly require 24 different dietary compositions to maximise their fitness. Here we move from identifying sex-25 specific optimal diets to understanding the molecular mechanisms that underlie male and 26 female responses to dietary variation. We examine male and female gene expression on male-27 optimal (carbohydrate-rich) and female-optimal (protein-rich) diets. We find that the sexes 28 share a large core of metabolic genes that are concordantly regulated in response to dietary 29 composition. However, we also observe smaller sets of genes with divergent and opposing 30 regulation, most notably in reproductive genes which are over-expressed on each sex's 31 optimal diet. Our results suggest that nutrient sensing output emanating from a shared 32 metabolic machinery are reversed in males and females, leading to opposing diet-dependent 33 regulation of reproduction in males and females. Further analysis and experiments suggest 34 that this reverse regulation occurs within the IIS/TOR network. 35 36 [3]. 46Studies in insect species [3][4][5][6][7] have shown that the two sexes require different diets to 47 maximise fitness. Female fitness is typically maximised on a high concentration of protein, 48 which fulfils the demands of producing and provisioning eggs. Males, in contrast, achieve 49 optimal fitness with a diet consisting of more carbohydrate, which can fuel activities such as 50 locating and attracting mates. Work on nutritional choices has shown that individuals tailor 51 their diet in line with their physiological needs. In insects, females overall prefer diets with 52 higher protein content, whereas males chose a more carbohydrate-rich diet [8, 9]. These 53 choices are further adapted to reflect the individual's current condition and reproductive 54 investment [9, 10]. For example, Camus et al. [11] found that the female preference for 55 protein in fruit flies was significantly higher in mated females (who require resources to 56 produce eggs) than virgins, while the preferences of males (who start producing sperm before 57 reaching sexual maturity) did not significantly differ between mated and virgin flies. 58But individuals not only choose diets to suit their needs where possible, they also adapt 59 their physiology and reproductive investment in response to the quality and quantity of 60 nutrition available. This has been studied extensively using experiments that either alter the 61 macronutrients composition (carbohydrates vs. protein) of the diet while keeping the overall 62 caloric intent constant, or by manipulating the overall nutrient content of the food-dietary 63 restriction (DR). These studies have shown that a wide range of life history traits respond to 64 changes in both the composition of the food [7, 12, 13] and the quantity of nutrients supplied 65 [14][15][16]. For example, DR typically causes an extension of lifespan at the cost of reduced 66reproduction [17], and a similar response can be triggered ...

Nutrition shapes a broad range of life-history traits, ultimately impacting animal fitness. A key fitness-related trait, female fecundity is well known to change as a function of diet. In particular, the availability of dietary protein is one of the main drivers of egg production, and in the absence of essential amino acids egg laying declines. However, it is unclear whether all essential amino acids have the same impact on phenotypes like fecundity. Using a holidic diet, we fed adult female Drosophila melanogaster diets that contained all necessary nutrients except one of the 10 essential amino acids and assessed the effects on egg production. For most essential amino acids, depleting a single amino acid induced as rapid a decline in egg production as when there were no amino acids in the diet. However, when either methionine or histidine were excluded from the diet, egg production declined more slowly. Next, we tested whether GCN2 and TOR mediated this difference in response across amino acids. While mutations in GCN2 did not eliminate the differences in the rates of decline in egg laying among amino acid drop-out diets, we found that inhibiting TOR signalling caused egg laying to decline rapidly for all drop-out diets. TOR signalling does this by regulating the yolk-forming stages of egg chamber development. Our results suggest that amino acids differ in their ability to induce signalling via the TOR pathway. This is important because if phenotypes differ in sensitivity to individual amino acids, this generates the potential for mismatches between the output of a pathway and the animal’s true nutritional status.

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