The neuropeptide drosulfakinin enhances choosiness and protects males from the aging effects of social perception.

The motivation to reproduce is a potent natural drive, and the social behaviors that induce it can severely impact animal health and lifespan. Indeed, in males, accelerated aging associated with reproduction arises not from the physical act of courtship or copulation but instead from the motivational drive to court and mate. To better understand the mechanisms underlying social effects on aging, we studied male choosiness for mates.

Behavioral dissection of hunger states in .

Hunger is a motivational drive that promotes feeding, and it can be generated by the physiological need to consume nutrients as well as the hedonic properties of food. Brain circuits and mechanisms that regulate feeding have been described, but which of these contribute to the generation of motive forces that drive feeding is unclear. Here, we describe our first efforts at behaviorally and neuronally distinguishing hedonic from homeostatic hunger states in and propose that this system can be used as a model to dissect the molecular mechanisms that underlie feeding motivation.

Ring neurons in the Drosophila central complex act as a rheostat for sensory modulation of aging.

Sensory perception modulates aging, yet we know little about how. An understanding of the neuronal mechanisms through which animals orchestrate biological responses to relevant sensory inputs would provide insight into the control systems that may be important for modulating lifespan. Here, we provide new awareness into how the perception of dead conspecifics, or death perception, which elicits behavioral and physiological effects in many different species, affects lifespan in the fruit fly, Drosophila melanogaster.

Light modulates lifespan via perceptual systems independent of circadian rhythms.

Across taxa, sensory perception modulates aging in response to important ecological cues, including food, sex, and danger. The range of sensory cues involved, and their mechanism of action, are largely unknown. We therefore sought to better understand how one potential cue, that of light, impacts aging in .

The serotonin receptor 5-HT2A modulates lifespan and protein feeding in .

The conserved neurotransmitter serotonin has been shown to be an important modulator of lifespan in specific nutritional contexts; however, it remained unclear how serotonin signaling influences lifespan under normal conditions. Here, we show that serotonin signaling through the 5-HT2A receptor influences lifespan, behavior, and physiology in . Loss of the 5-HT2A receptor extends lifespan and induces a resistance to changes in dietary protein that are normally detrimental to lifespan.

Lifespan extension in female mice by early, transient exposure to adult female olfactory cues.

Several previous lines of research have suggested, indirectly, that mouse lifespan is particularly susceptible to endocrine or nutritional signals in the first few weeks of life, as tested by manipulations of litter size, growth hormone levels, or mutations with effects specifically on early-life growth rate. The pace of early development in mice can also be influenced by exposure of nursing and weanling mice to olfactory cues. In particular, odors of same-sex adult mice can in some circumstances delay maturation.

Serotonin and dopamine modulate aging in response to food odor and availability.

An organism's ability to perceive and respond to changes in its environment is crucial for its health and survival. Here we reveal how the most well-studied longevity intervention, dietary restriction, acts in-part through a cell non-autonomous signaling pathway that is inhibited by the presence of attractive smells. Using an intestinal reporter for a key gene induced by dietary restriction but suppressed by attractive smells, we identify three compounds that block food odor effects in C.

Serotonin signaling modulates aging-associated metabolic network integrity in response to nutrient choice in Drosophila melanogaster.

Aging arises from complex interactions among multiple biochemical products. Systems-level analyses of biological networks may provide insights into the causes and consequences of aging that evade single-gene studies. We have previously found that dietary choice is sufficient to modulate aging in the vinegar fly, Drosophila melanogaster.

Yeast volatiles double starvation survival in .

Organisms make decisions based on the information they gather from their environment, the effects of which affect their fitness. Understanding how these interactions affect physiology may generate interventions that improve the length and quality of life. Here, we provide evidence that exposure to live yeast volatiles during starvation significantly extends survival, increases activity, and slows the rate of triacylglyceride (TAG) decline independent of canonical sensory perception.

serotonin 2A receptor signaling coordinates central metabolic processes to modulate aging in response to nutrient choice.

It has been recognized for nearly a century that diet modulates aging. Despite early experiments suggesting that reduced caloric intake augmented lifespan, accumulating evidence indicates that other characteristics of the diet may be equally or more influential in modulating aging. We demonstrate that behavior, metabolism, and lifespan in are affected by whether flies are provided a choice of different nutrients or a single, complete medium, largely independent of the amount of nutrients that are consumed.

Cell non-autonomous regulation of health and longevity.

As the demographics of the modern world skew older, understanding and mitigating the effects of aging is increasingly important within biomedical research. Recent studies in model organisms demonstrate that the aging process is frequently modified by an organism's ability to perceive and respond to changes in its environment. Many well-studied pathways that influence aging involve sensory cells, frequently neurons, that signal to peripheral tissues and promote survival during the presence of stress.

High-throughput small molecule screening reveals Nrf2-dependent and -independent pathways of cellular stress resistance.

Aging is the dominant risk factor for most chronic diseases. Development of antiaging interventions offers the promise of preventing many such illnesses simultaneously. Cellular stress resistance is an evolutionarily conserved feature of longevity.

The metabolome as a link in the genotype-phenotype map for peroxide resistance in the fruit fly, Drosophila melanogaster.

Background: Genetic association studies that seek to explain the inheritance of complex traits typically fail to explain a majority of the heritability of the trait under study. Thus, we are left with a gap in the map from genotype to phenotype. Several approaches have been used to fill this gap, including those that attempt to map endophenotype such as the transcriptome, proteome or metabolome, that underlie complex traits.

Neuronal Mechanisms that Drive Organismal Aging Through the Lens of Perception.

Sensory neurons provide organisms with data about the world in which they live, for the purpose of successfully exploiting their environment. The consequences of sensory perception are not simply limited to decision-making behaviors; evidence suggests that sensory perception directly influences physiology and aging, a phenomenon that has been observed in animals across taxa. Therefore, understanding the neural mechanisms by which sensory input influences aging may uncover novel therapeutic targets for aging-related physiologies.

Neuronal-specific proteasome augmentation via Prosβ5 overexpression extends lifespan and reduces age-related cognitive decline.

Cognitive function declines with age throughout the animal kingdom, and increasing evidence shows that disruption of the proteasome system contributes to this deterioration. The proteasome has important roles in multiple aspects of the nervous system, including synapse function and plasticity, as well as preventing cell death and senescence. Previous studies have shown neuronal proteasome depletion and inhibition can result in neurodegeneration and cognitive deficits, but it is unclear if this pathway is a driver of neurodegeneration and cognitive decline in aging.

Dietary yeast influences ethanol sedation in Drosophila via serotonergic neuron function.

Abuse of alcohol is a major clinical problem with far-reaching health consequences. Understanding the environmental and genetic factors that contribute to alcohol-related behaviors is a potential gateway for developing novel therapeutic approaches for patients that abuse the drug. To this end, we have used Drosophila melanogaster as a model to investigate the effect of diet, an environmental factor, on ethanol sedation.

Sensory perception of dead conspecifics induces aversive cues and modulates lifespan through serotonin in Drosophila.

Sensory perception modulates health and aging across taxa. Understanding the nature of relevant cues and the mechanisms underlying their action may lead to novel interventions that improve the length and quality of life. We found that in the vinegar fly, Drosophila melanogaster, exposure to dead conspecifics in the environment induced cues that were aversive to other flies, modulated physiology, and impaired longevity.

High Dietary Sugar Reshapes Sweet Taste to Promote Feeding Behavior in Drosophila melanogaster.

Recent studies find that sugar tastes less intense to humans with obesity, but whether this sensory change is a cause or a consequence of obesity is unclear. To tackle this question, we study the effects of a high sugar diet on sweet taste sensation and feeding behavior in Drosophila melanogaster. On this diet, fruit flies have lower taste responses to sweet stimuli, overconsume food, and develop obesity.

Measurement of solid food intake in Drosophila via consumption-excretion of a dye tracer.

Although the Drosophila melanogaster (fly) model is a popular platform for investigating diet-related phenomena, it can be challenging to measure the volume of agar-based food media flies consume. We addressed this challenge by developing a dye-based method called Consumption-Excretion (Con-Ex). In Con-Ex studies, flies consume solid food labeled with dye, and the volume of food consumed is reflected by the sum of the dye inside of and excreted by flies.

MicroRNAs mir-184 and let-7 alter Drosophila metabolism and longevity.

MicroRNAs (miRNAs) are small RNA molecules that regulate gene expression associated with many complex biological processes. By comparing miRNA expression between long-lived cohorts of Drosophila melanogaster that were fed a low-nutrient diet with normal-lived control animals fed a high-nutrient diet, we identified miR-184, let-7, miR-125, and miR-100 as candidate miRNAs involved in modulating aging. We found that ubiquitous, adult-specific overexpression of these individual miRNAs led to significant changes in fat metabolism and/or lifespan.

Tissue-specific insulin signaling mediates female sexual attractiveness.

Individuals choose their mates so as to maximize reproductive success, and one important component of this choice is assessment of traits reflecting mate quality. Little is known about why specific traits are used for mate quality assessment nor about how they reflect it. We have previously shown that global manipulation of insulin signaling, a nutrient-sensing pathway governing investment in survival versus reproduction, affects female sexual attractiveness in the fruit fly, Drosophila melanogaster.

Perceptive costs of reproduction drive ageing and physiology in male Drosophila.

Costs of reproduction are thought to result from natural selection optimizing organismal fitness within putative physiological constraints. Phenotypic and population genetic studies of reproductive costs are plentiful across taxa, but an understanding of their mechanistic basis would provide important insight into the diversity in life-history traits, including reproductive effort and ageing. Here, we dissect the causes and consequences of specific costs of reproduction in male Drosophila melanogaster.

Acute Dietary Restriction Acts via TOR, PP2A, and Myc Signaling to Boost Innate Immunity in Drosophila.

Dietary restriction promotes health and longevity across taxa through mechanisms that are largely unknown. Here, we show that acute yeast restriction significantly improves the ability of adult female Drosophila melanogaster to resist pathogenic bacterial infections through an immune pathway involving downregulation of target of rapamycin (TOR) signaling, which stabilizes the transcription factor Myc by increasing the steady-state level of its phosphorylated forms through decreased activity of protein phosphatase 2A. Upregulation of Myc through genetic and pharmacological means mimicked the effects of yeast restriction in fully fed flies, identifying Myc as a pro-immune molecule.

Proteomics and metabolomics in ageing research: from biomarkers to systems biology.

Age is the single greatest risk factor for a wide range of diseases, and as the mean age of human populations grows steadily older, the impact of this risk factor grows as well. Laboratory studies on the basic biology of ageing have shed light on numerous genetic pathways that have strong effects on lifespan. However, we still do not know the degree to which the pathways that affect ageing in the lab also influence variation in rates of ageing and age-related disease in human populations.

Drosophila Neuropeptide F Signaling Independently Regulates Feeding and Sleep-Wake Behavior.

Proper regulation of sleep-wake behavior and feeding is essential for organismal health and survival. While previous studies have isolated discrete neural loci and substrates important for either sleep or feeding, how the brain is organized to coordinate both processes with respect to one another remains poorly understood. Here, we provide evidence that the Drosophila Neuropeptide F (NPF) network forms a critical component of both adult sleep and feeding regulation.