Con-DAM: Simultaneous measurement of food intake and sleep in at the single fly resolution.

Sleep and feeding are conserved behaviors across many taxa of the animal kingdom and are essential for an organism's survival and fitness. Although has been used to study these behaviors for decades, concurrent measurement of these two behaviors in the same flies on solid media has been a challenge. Here, we report Con-DAM, which enables simultaneous quantification of food intake and sleep/activity at the single fly resolution.

Temperature-driven coordination of circadian transcriptional regulation.

The circadian clock is an evolutionarily-conserved molecular oscillator that enables species to anticipate rhythmic changes in their environment. At a molecular level, the core clock genes induce circadian oscillations in thousands of genes in a tissue-specific manner, orchestrating myriad biological processes. While previous studies have investigated how the core clock circuit responds to environmental perturbations such as temperature, the downstream effects of such perturbations on circadian regulation remain poorly understood.

Dietary restriction fails to extend lifespan of Drosophila model of Werner syndrome.

Werner syndrome (WS) is a rare genetic disease in humans, caused by mutations in the WRN gene that encodes a protein containing helicase and exonuclease domains. WS is characterized by symptoms of accelerated aging in multiple tissues and organs, involving increased risk of cancer, heart failure, and metabolic dysfunction. These conditions ultimately lead to the premature mortality of patients with WS.

Con-FLIC: concurrent measurement of feeding behaviors and food consumption in at single-fly resolution.

Accurate quantification of food intake and feeding behaviors are essential for understanding various biological processes, such as metabolism and aging. Currently, no methods allow for the concurrent measurement of both parameters for the same individual flies. Here, we couple Con-Ex ( Con sumption- Ex cretion) and FLIC ( F ly L iquid-Food I nteraction C ounter), previously developed to measure food consumption and various feeding behaviors, respectively, into a single platform that we named Con-FLIC.

Temperature-driven coordination of circadian transcriptome regulation.

The circadian rhythm is an evolutionarily-conserved molecular oscillator that enables species to anticipate rhythmic changes in their environment. At a molecular level, the core clock genes induce a circadian oscillation in thousands of genes in a tissue-specific manner, orchestrating myriad biological processes. While studies have investigated how the core clock circuit responds to environmental perturbations such as temperature, the downstream effects of such perturbations on circadian regulation remain poorly understood.

Dietary Restriction Impacts Peripheral Circadian Clock Output Important for Longevity in .

Circadian clocks may mediate lifespan extension by caloric or dietary restriction (DR). We find that the core clock transcription factor is crucial for a robust longevity and fecundity response to DR in . To identify clock-controlled mediators, we performed RNA-sequencing from abdominal fat bodies across the 24 h day after just 5 days under control or DR diets.

Roles of peripheral clocks: lessons from the fly.

To adapt to and anticipate rhythmic changes in the environment such as daily light-dark and temperature cycles, internal timekeeping mechanisms called biological clocks evolved in a diverse set of organisms, from unicellular bacteria to humans. These biological clocks play critical roles in organisms' fitness and survival by temporally aligning physiological and behavioral processes to the external cues. The central clock is located in a small subset of neurons in the brain and drives daily activity rhythms, whereas most peripheral tissues harbor their own clock systems, which generate metabolic and physiological rhythms.

Mechanisms of Lifespan Regulation by Calorie Restriction and Intermittent Fasting in Model Organisms.

Genetic and pharmacological interventions have successfully extended healthspan and lifespan in animals, but their genetic interventions are not appropriate options for human applications and pharmacological intervention needs more solid clinical evidence. Consequently, dietary manipulations are the only practical and probable strategies to promote health and longevity in humans. Caloric restriction (CR), reduction of calorie intake to a level that does not compromise overall health, has been considered as being one of the most promising dietary interventions to extend lifespan in humans.

Control of apoptosis by Drosophila DCAF12.

Regulated Apoptosis (Programmed Cell Death, PCD) maintains tissue homeostasis in adults, and ensures proper growth and morphogenesis of tissues during development of metazoans. Accordingly, defects in cellular processes triggering or executing apoptotic programs have been implicated in a variety of degenerative and neoplastic diseases. Here, we report the identification of DCAF12, an evolutionary conserved member of the WD40-motif repeat family of proteins, as a new regulator of apoptosis in Drosophila.

Genetics of Circadian Rhythms.

Nearly all organisms exhibit time-dependent behavior and physiology across a 24-hour day known as circadian rhythms. These outputs are manifestations of endogenous cyclic gene expression patterns driven by the activity of a core transcription/translation feedback loop. Cyclic gene expression determines highly tissue-specific functional activity regulating such processes as metabolic state, endocrine activity, and neural excitability.

Notch-mediated suppression of TSC2 expression regulates cell differentiation in the Drosophila intestinal stem cell lineage.

Epithelial homeostasis in the posterior midgut of Drosophila is maintained by multipotent intestinal stem cells (ISCs). ISCs self-renew and produce enteroblasts (EBs) that differentiate into either enterocytes (ECs) or enteroendocrine cells (EEs) in response to differential Notch (N) activation. Various environmental and growth signals dynamically regulate ISC activity, but their integration with differentiation cues in the ISC lineage remains unclear.

The functional costs and benefits of dietary restriction in Drosophila.

Dietary restriction (DR) extends lifespan in an impressively wide array of species spanning three eukaryotic kingdoms. In sharp contrast, relatively little is known about the effects of DR on functional senescence, with most of the work having been done on mice and rats. Here we used Drosophila melanogaster to test the assumption that lifespan extension through DR slows down age-related functional deterioration.

Drosophila dFOXO controls lifespan and regulates insulin signalling in brain and fat body.

In Drosophila melanogaster, ageing is slowed when insulin-like signalling is reduced: life expectancy is extended by more than 50% when the insulin-like receptor (InR) or its receptor substrate (chico) are mutated, or when insulin-producing cells are ablated. But we have yet to resolve when insulin affects ageing, or whether insulin signals regulate ageing directly or indirectly through secondary hormones. Caenorhabditis elegans lifespan is also extended when insulin signalling is inhibited in certain tissues, or when repressed in adult worms, and this requires the forkhead transcription factor (FOXO) encoded by daf-16 (ref.

Different age-specific demographic profiles are generated in the same normal-lived Drosophila strain by different longevity stimuli.

We review the empirical data obtained with our normal-lived Ra control strain of Drosophila and show that this one genome is capable of invoking at least three different responses to external stimuli that induce the animal to express one of three different extended longevity phenotypes, each of which arises from one of three different antagonistic molecular mechanisms of stress resistance. The phenotypes are distinguished by different age-specific mortality patterns. Depending on the selected mechanism, the genome may respond by expressing a delayed onset of senescence (type 1), an increased early survival (type 2), or an increased late survival (type 3) phenotype, suggesting their different demographic effects.

Genomic plasticity, energy allocations, and the extended longevity phenotypes of Drosophila.

The antagonistic pleiotropy theory of the evolution of aging is shown to be too simple to fully apply to the situation in which Drosophila are selected directly for delayed female fecundity and indirectly for extended longevity. We re-evaluated our own previously reported selection experiments using previously unreported data, as well as new data from the literature. The facts that led to this re-evaluation were: (1) the recognition that there are at least three different extended longevity phenotypes; (2) the existence of metabolic and mitochondrial differences between normal- and long-lived organisms; and most importantly; (3) the observation that animals selected for extended longevity are both more fecund and longer-lived than their progenitor control animals.

Metabolic alterations and shifts in energy allocations are corequisites for the expression of extended longevity genes in Drosophila.

Evolutionary theories suggest that the expression of extended longevity depends on the organism's ability to shift energy from reproduction to somatic maintenance. New data led us to reexamine our older data and integrate the two into a larger picture of the genetic and metabolic alterations required if the animal is to live long. Our Ra normal-lived control strain can express any one of three different extended longevity phenotypes, only one of which involves significant and proportional increases in both mean and maximum longevity and thus a delayed onset of senescence.