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

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 . We examine male and female gene expression on male-optimal (carbohydrate-rich) and female-optimal (protein-rich) diets.

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.

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.

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.

Protocols to Study Aging in Drosophila.

The fruit fly Drosophila melanogaster offers a host of advantages for studying the biology of aging: a well-understood biology, a wide range of genetic reagents, well-defined dietary requirements, and a relatively short life span, with a median of ~80 days and maximum ~100 days. Several phenotypes can be used to assess the aging process, but the simplest and most widely used metric is length of life. Here we describe a standard life span assay for Drosophila housed on a simple sugar/yeast diet.

Nuclear hormone receptor DHR96 mediates the resistance to xenobiotics but not the increased lifespan of insulin-mutant Drosophila.

Lifespan of laboratory animals can be increased by genetic, pharmacological, and dietary interventions. Increased expression of genes involved in xenobiotic metabolism, together with resistance to xenobiotics, are frequent correlates of lifespan extension in the nematode worm Caenorhabditis elegans, the fruit fly Drosophila, and mice. The Green Theory of Aging suggests that this association is causal, with the ability of cells to rid themselves of lipophilic toxins limiting normal lifespan.

QuantiFly: Robust Trainable Software for Automated Drosophila Egg Counting.

We report the development and testing of software called QuantiFly: an automated tool to quantify Drosophila egg laying. Many laboratories count Drosophila eggs as a marker of fitness. The existing method requires laboratory researchers to count eggs manually while looking down a microscope.

Using doubly-labeled water to measure energy expenditure in an important small ectotherm Drosophila melanogaster.

Energy expenditure is a key variable in the study of ageing, and the fruit fly Drosophila melanogaster is a model organism that has been used to make step changes in our understanding of the ageing process. Standard methods for measurement of energy expenditure involve placing individuals in metabolic chambers where their oxygen consumption and CO2 production can be quantified. These measurements require separating individuals from any social context, and may only poorly reflect the environment in which the animals normally live.

Target of rapamycin signalling mediates the lifespan-extending effects of dietary restriction by essential amino acid alteration.

Dietary restriction (DR), defined as a moderate reduction in food intake short of malnutrition, has been shown to extend healthy lifespan in a diverse range of organisms, from yeast to primates. Reduced signalling through the insulin/IGF-like (IIS) and Target of Rapamycin (TOR) signalling pathways also extend lifespan. InDrosophila melanogaster the lifespan benefits of DR can be reproduced by modulating only the essential amino acids in yeast based food.

A holidic medium for Drosophila melanogaster.

A critical requirement for research using model organisms is a well-defined and consistent diet. There is currently no complete chemically defined (holidic) diet available for Drosophila melanogaster. We describe a holidic medium that is equal in performance to an oligidic diet optimized for adult fecundity and lifespan.

Analysing variation in Drosophila aging across independent experimental studies: a meta-analysis of survival data.

Survival records of longevity experiments are a key component in research on aging. However, surprisingly there have been very few cross-study analyses, besides comparisons of median lifespans or similar summary information. Here, we use a large set of full survival data from various studies to address questions in aging, which are beyond the scope of individual studies.

Detrimental effects of RNAi: a cautionary note on its use in Drosophila ageing studies.

RNA interference (RNAi) provides an important tool for gene function discovery. It has been widely exploited in Caenorhabditis elegans ageing research because it does not appear to have any non-specific effects on ageing-related traits in that model organism. We show here that ubiquitous, adult-onset activation of the RNAi machinery, achieved by expressing a double stranded RNA targeting GFP or lacZ for degradation, or by increasing expression of Dicer substantially reduces lifespan in Drosophila melanogaster.

Absence of effects of Sir2 overexpression on lifespan in C. elegans and Drosophila.

Overexpression of sirtuins (NAD(+)-dependent protein deacetylases) has been reported to increase lifespan in budding yeast (Saccharomyces cerevisiae), Caenorhabditis elegans and Drosophila melanogaster. Studies of the effects of genes on ageing are vulnerable to confounding effects of genetic background. Here we re-examined the reported effects of sirtuin overexpression on ageing and found that standardization of genetic background and the use of appropriate controls abolished the apparent effects in both C.

Dietary restriction and aging: a unifying perspective.

Dietary restriction (DR) and mutations in nutrient signaling pathways can extend healthy life span in diverse organisms. Studying the interaction between these interventions should reveal mechanisms of aging, but has yielded some apparently contradictory results. A multidimensional representation of nutrition, called the geometric framework, can better describe the responses of life span and other traits, including metabolism, and can reconcile these apparent contradictions.

Amino-acid imbalance explains extension of lifespan by dietary restriction in Drosophila.

Dietary restriction extends healthy lifespan in diverse organisms and reduces fecundity. It is widely assumed to induce adaptive reallocation of nutrients from reproduction to somatic maintenance, aiding survival of food shortages in nature. If this were the case, long life under dietary restriction and high fecundity under full feeding would be mutually exclusive, through competition for the same limiting nutrients.

Quantification of food intake in Drosophila.

Measurement of food intake in the fruit fly Drosophila melanogaster is often necessary for studies of behaviour, nutrition and drug administration. There is no reliable and agreed method for measuring food intake of flies in undisturbed, steady state, and normal culture conditions. We report such a method, based on measurement of feeding frequency by proboscis-extension, validated by short-term measurements of food dye intake.

Effect of a standardised dietary restriction protocol on multiple laboratory strains of Drosophila melanogaster.

Background: Outcomes of lifespan studies in model organisms are particularly susceptible to variations in technical procedures. This is especially true of dietary restriction, which is implemented in many different ways among laboratories.

Principal Findings: In this study, we have examined the effect of laboratory stock maintenance, genotype differences and microbial infection on the ability of dietary restriction (DR) to extend life in the fruit fly Drosophila melanogaster.

Diet and aging.

Interventions that extend life span by moderately reduced nutrient intake are often referred to as dietary or calorie restriction. Its efficacy in many species has led to the conclusion that a single, evolutionarily conserved, molecular mechanism operates in all cases to extend life. Here we discuss examples of diet/genotype interactions that show a more complex mechanistic view is required and that mild dietary modifications can dramatically change the interpretation of model organism aging studies.

Evidence for lifespan extension and delayed age-related biomarkers in insulin receptor substrate 1 null mice.

Recent evidence suggests that alterations in insulin/insulin-like growth factor 1 (IGF1) signaling (IIS) can increase mammalian life span. For example, in several mouse mutants, impairment of the growth hormone (GH)/IGF1 axis increases life span and also insulin sensitivity. However, the intracellular signaling route to altered mammalian aging remains unclear.

Optimization of dietary restriction protocols in Drosophila.

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.

Evolutionary conservation of regulated longevity assurance mechanisms.

Background: To what extent are the determinants of aging in animal species universal? Insulin/insulin-like growth factor (IGF)-1 signaling (IIS) is an evolutionarily conserved (public) regulator of longevity; yet it remains unclear whether the genes and biochemical processes through which IIS acts on aging are public or private (that is, lineage specific). To address this, we have applied a novel, multi-level cross-species comparative analysis to compare gene expression changes accompanying increased longevity in mutant nematodes, fruitflies and mice with reduced IIS.

Results: Surprisingly, there is little evolutionary conservation at the level of individual, orthologous genes or paralogous genes under IIS regulation.

Dietary restriction in Drosophila: delayed aging or experimental artefact?

Lifespan can be extended by reduction of dietary intake. This practice is referred to as dietary restriction (DR), and extension of lifespan by DR is evolutionarily conserved in taxonomically diverse organisms including yeast, invertebrates, and mammals. Although these two often-stated facts carry the implication that the mechanisms of DR are also evolutionarily conserved, extension of lifespan could be a case of evolutionary convergence, with different underlying mechanisms in different taxa.

Transcriptional responses of Saccharomyces cerevisiae to preferred and nonpreferred nitrogen sources in glucose-limited chemostat cultures.

Aerobic, glucose-limited chemostat cultures of Saccharomyces cerevisiae grown with six different nitrogen sources were subjected to transcriptome analysis. The use of chemostats enabled an analysis of nitrogen-source-dependent transcriptional regulation at a fixed specific growth rate. A selection of preferred (ammonium and asparagine) and nonpreferred (leucine, phenylalanine, methionine and proline) nitrogen sources was investigated.

Coordinated multitissue transcriptional and plasma metabonomic profiles following acute caloric restriction in mice.

Caloric restriction (CR) increases healthy life span in a range of organisms. The underlying mechanisms are not understood but appear to include changes in gene expression, protein function, and metabolism. Recent studies demonstrate that acute CR alters mortality rates within days in flies.