David Raubenheimer

Lifespan and reproduction in Drosophila: New insights from nutritional geometry

Modest dietary restriction (DR) prolongs life in a wide range of organisms, spanning single-celled yeast to mammals. Here, we report the use of recent techniques in nutrition research to quantify the detailed relationship between diet, nutrient intake, lifespan, and reproduction in Drosophila melanogaster. Caloric restriction (CR) was not responsible for extending lifespan in our experimental flies. Response surfaces for lifespan and fecundity were maximized at different protein–carbohydrate intakes, with longevity highest at a protein-to-carbohydrate ratio of 1:16 and egg-laying rate maximized at 1:2. Lifetime egg production, the measure closest to fitness, was maximized at an intermediate P:C ratio of 1:4. Flies offered a choice of complementary foods regulated intake to maximize lifetime egg production. The results indicate a role for both direct costs of reproduction and other deleterious consequences of ingesting high levels of protein. We unite a body of apparently conflicting work within a common framework and provide a platform for studying aging in all organisms.

The Ratio of Macronutrients, Not Caloric Intake, Dictates Cardiometabolic Health, Aging, and Longevity in Ad Libitum-Fed Mice

The fundamental questions of what represents a macronutritionally balanced diet and how this maintains health and longevity remain unanswered. Here, the Geometric Framework, a state-space nutritional modeling method, was used to measure interactive effects of dietary energy, protein, fat, and carbohydrate on food intake, cardiometabolic phenotype, and longevity in mice fed one of 25 diets ad libitum. Food intake was regulated primarily by protein and carbohydrate content. Longevity and health were optimized when protein was replaced with carbohydrate to limit compensatory feeding for protein and suppress protein intake. These consequences are associated with hepatic mammalian target of rapamycin (mTOR) activation and mitochondrial function and, in turn, related to circulating branched-chain amino acids and glucose. Calorie restriction achieved by high-protein diets or dietary dilution had no beneficial effects on lifespan. The results suggest that longevity can be extended in ad libitum-fed animals by manipulating the ratio of macronutrients to inhibit mTOR activation.

Analysis of covariance: an alternative to nutritional indices

Some statistical problems are added to the growing list of cautionary tales regarding the use of the conventional, ratio‐based nutritional indices (RCR, RGR, ECI, AD and ECD). Analysis of ratios is based on the, probably unrealistic, assumption of an isometric relationship between denominator and numerator variables. Analysis of covariance (ANCOVA) makes less restrictive assumptions, and additionally provides important information about the data which is lost by using ratio variables. We demonstrate, using computer‐generated data sets, some of the pitfalls of statistical analysis of ratios and illustrate how these may be avoided using ANCOVA. Some possible consequences of such statistical iniquities for biological interpretations are discussed.

Obesity: the protein leverage hypothesis

The obesity epidemic is among the greatest public health challenges facing the modern world. Regarding dietary causes, most emphasis has been on changing patterns of fat and carbohydrate consumption. In contrast, the role of protein has largely been ignored, because (i) it typically comprises only ∼15% of dietary energy, and (ii) protein intake has remained near constant within and across populations throughout the development of the obesity epidemic. We show that, paradoxically, these are precisely the two conditions that potentially provide protein with the leverage both to drive the obesity epidemic through its effects on food intake, and perhaps to assuage it. We formalize this hypothesis in a mathematical model. Some supporting epidemiological, experimental and animal data are presented, and predictions are made for future testing.

Sex-Specific Fitness Effects of Nutrient Intake on Reproduction and Lifespan

Diet affects both lifespan and reproduction [1-9], leading to the prediction that the contrasting reproductive strategies of the sexes should result in sex-specific effects of nutrition on fitness and longevity [6, 10] and favor different patterns of nutrient intake in males and females. However, males and females share most of their genome and intralocus sexual conflict may prevent sex-specific diet optimization. We show that both male and female longevity were maximized on a high-carbohydrate low-protein diet in field crickets Teleogryllus commodus, but male and female lifetime reproductive performances were maximized in markedly different parts of the nutrient intake landscape. Given a choice, crickets exhibited sex-specific dietary preference in the direction that increases reproductive performance, but this sexual dimorphism in preference was incomplete, with both sexes displaced from the optimum diet for lifetime reproduction. Sexes are, therefore, constrained in their ability to reach their sex-specific dietary optima by the shared biology of diet choice. Our data suggest that sex-specific selection has thus far failed fully to resolve intralocus sexual conflict over diet optimization. Such conflict may be an important factor linking nutrition and reproduction to lifespan and aging.

Flexible diet choice offsets protein costs of pathogen resistance in a caterpillar

Mounting effective resistance against pathogens is costly in terms of energy and nutrients. However, it remains unexplored whether hosts can offset such costs by adjusting their dietary intake so as to recoup the specific resources involved. We test this possibility by experimentally challenging caterpillars (Spodoptera littoralis) with a highly virulent entomopathogen (nucleopolyhedrovirus), under dietary regimes varying in the content of protein and digestible carbohydrate. We found that dietary protein influenced both resistance to pathogen attack and constitutive immune function to a greater extent than did dietary carbohydrate, indicating higher protein costs of resistance than energy costs. Moreover, when allowed to self-compose their diet, insects surviving viral challenge increased their relative intake of protein compared with controls and those larvae dying of infection, thus demonstrating compensation for protein costs associated with resistance. These results suggest that the change in the hosts nutritional demands to fight infection induces a compensatory shift in feeding behaviour.

Integrating nutrition: a geometrical approach

We present and illustrate using data from insects an integrative approach to modelling animal nutrition. This framework enables the unification within simple geometrical models of several nutritionally relevant measures. These include: the optimal balance and amounts of nutrients required to be ingested and allocated to growth by an animal over a given time period (the intake and growth targets, respectively); the animals current state in relation to these requirements; available foods and the consequences for the animals state of ingesting them; the amounts of ingested nutrients that are retained and eliminated; and animal performance. Data are presented on intake targets in insects, illustrating how they change over various time-scales (physiological, developmental, and evolutionary). Most importantly, the geometrical approach enables a clear description to be made of the tradeoffs reached by animals in regulating their nutritional balance. Animals given a nutritionally balanced food, or two or more imbalanced but complementary foods, can satisfy their nutrient requirements. However, those eating non-complementary imbalanced foods must reach a suitable compromise between over-ingesting some nutrients and under-ingesting others. Data are presented comparing the rules of compromise for protein and carbohydrate ingestion in grass-feeding (Locusta migratoria) and polyphagous (Schistocerca gregaria) locusts.

Nutrient balancing in grasshoppers: behavioural and physiological correlates of dietary breadth

SUMMARY We examined correlates of nutrient balancing with dietary range by comparing diet selection and ingestive, post-ingestive and performance-related responses to macronutrient imbalance in two species of grasshopper. One of the two species, Locusta migratoria (the African migratory locust), is a specialist grass-feeder, while the other, Schistocerca gregaria (the desert locust), is a generalist herbivore that includes both grasses and forbs in its diet. In ad libitum conditions, both species composed a balanced intake of the two macronutrients protein and carbohydrate from nutritionally complementary synthetic foods, but the composition of the selected diet differed, with the generalist selecting more protein, but not carbohydrate, than the grass-specialist. The grass-specialist, by contrast, retained ingested nitrogen more efficiently on the ad libitum diets. When confined to nutritionally imbalanced foods, both species regulated ingestion in such a way as to mitigate excesses as well as deficits of the two nutrients. The responses were, however, distinct in the two species, with the generalist feeder ingesting greater excesses of protein than the specialist. The species also differed in their post-ingestive responses to ingested excesses of nutrient, with the generalist but not the specialist using protein-derived carbon as an energy source when fed carbohydrate-deficient foods. The generalist also retained a higher level of body protein when confined to protein-deficient diets. The data suggested one functional reason why the generalist species selected a diet with higher protein content in the ad libitum treatment because, when confined to the nutritionally imbalanced foods, development rate peaked on higher protein foods for the generalist compared with the specialist. Many aspects of these data agree with the prediction that generalist-feeding animals should show greater behavioural and physiological flexibility in their responses to nutrient imbalance than do specialists.

Modelling the ecological niche from functional traits

The niche concept is central to ecology but is often depicted descriptively through observing associations between organisms and habitats. Here, we argue for the importance of mechanistically modelling niches based on functional traits of organisms and explore the possibilities for achieving this through the integration of three theoretical frameworks: biophysical ecology (BE), the geometric framework for nutrition (GF) and dynamic energy budget (DEB) models. These three frameworks are fundamentally based on the conservation laws of thermodynamics, describing energy and mass balance at the level of the individual and capturing the prodigious predictive power of the concepts of ‘homeostasis’ and ‘evolutionary fitness’. BE and the GF provide mechanistic multi-dimensional depictions of climatic and nutritional niches, respectively, providing a foundation for linking organismal traits (morphology, physiology, behaviour) with habitat characteristics. In turn, they provide driving inputs and cost functions for mass/energy allocation within the individual as determined by DEB models. We show how integration of the three frameworks permits calculation of activity constraints, vital rates (survival, development, growth, reproduction) and ultimately population growth rates and species distributions. When integrated with contemporary niche theory, functional trait niche models hold great promise for tackling major questions in ecology and evolutionary biology.

THE GEOMETRIC ANALYSIS OF NUTRIENT–ALLELOCHEMICAL INTERACTIONS: A CASE STUDY USING LOCUSTS

We present the first data that comprehensively quantify the interactive effects on an herbivore of a plant allelochemical and dietary macronutrients. Locusts (Locusta migratoria) were reared across the fifth larval stadium on one of 20 foods with fixed total macronutrient content (42%), but varying in protein:carbohydrate (P:C) ratio (7:35, 14:28, 21:21, 28:14, or 35:7) and tannic acid (TA) content (0, 3.3, 6.7, or 10%). The effects of the allelochemical on consumption, nutrient uptake, body composition, development rate, and survivorship were highly dependent on the balance of macronutrients in the food. Mortality was low and independent of TA on the near-optimally balanced 21:21 food, but rose markedly with increasing TA levels as dietary P:C ratio became more unbalanced. The time course of deaths differed for excess P and excess C foods, suggesting different underlying causes. The major effect of TA in foods of low P:C ratio was to reduce the rate of intake, while TA in foods containing excess protein ...