54 research outputs found
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Does temperature preference change in aging flies?
Aging is known to be affected by many factors such as nutrition and exercise, and more studies are needed to understand the mechanisms of aging. Aging in flies shows many similarities with humans; therefore we study mechanisms of aging in flies as a model organism. Studying aging in flies requires knowledge of meaningful bio markers to measure quantitatively the rate of aging. In this study, I addressed the question of whether flies would change their temperatures preferences as they age. In a series of experiments, we sought out to compare if young flies showed the expected temperature preference rhythm (TPR).We then investigated whether the temperature preference is altered with age. We observed a trend for aging flies to lose the temperature preference rhythm. In addition, older flies preferred lower evening temperature compared to the young ones. While we were able to see a loss of temperature preference rhythm, we believe this is not a reliable or easy biomarker in the search for the measurable signs of aging.We set out to see if a biomarker of aging in could be found in temperance preference since it was found previously to be a predictable circadian rhythm in young flies. Since flies live 70 days it can be said that a day in the life of a fly is like a year in the life of a human. This is important because in our lab we use flies as a model organism for studying aging as to then apply to our understanding of human health and longevity. Currently most labs use over all lifespan as their biomarker of aging, but we need something that can be seen throughout the lifespan, not just at the end of it. We are always on the lookout for ways to see how aging effects the different conditions and genetic mutations we use. First we chose both wild types and genetic mutations to test for variation in results. We aged these flies at different intervals so as to have different ages to compare together. We further put these flies in alternating light-dark conditions to test together at different time points along the circadian 24 hour clock. The flies were tested in an apparatus that had a hot and cold side, with room temperature estimated in the middle along a temperature gradient that was established. There were 4 channels that separated the different groups of 50 individuals which labeled by their time of time, age, gender and genotype. After 30 minutes, a picture was taken to determine each of their temperature preference. No fly was retested and instead many bio repeats were used to establish a trend. Each fly was given a xy coordinate which a formula and computer program assigned a temperature to each. This data was averaged using statistical test and used to plot graphs of how the rhythm of temperature preference changed from young and old, and compared to the previously reported data
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Accelerated food source location in aging Drosophila
Adequate energy stores are essential for survival, and sophisticated neuroendocrine mechanisms evolved to stimulate foraging in response to nutrient deprivation. Food search behavior is usually investigated in young animals, and it is not known how aging alters this behavior. To address this question in Drosophila melanogaster, we compared the ability to locate food by olfaction in young and old flies using a food-filled trap. As aging is associated with a decline in motor functions, learning, and memory, we expected that aged flies would take longer to enter the food trap than their young counterparts. Surprisingly, old flies located food with significantly shorter latency than young ones. Robust food search behavior was associated with significantly lower fat reserves and lower starvation resistance in old flies. Food-finding latency (FFL) was shortened in young wild-type flies that were starved until their fat was depleted but also in heterozygous chico mutants with reduced insulin receptor activity and higher fat deposits. Conversely, food trap entry was delayed in old flies with increased insulin signaling. Our results suggest that the difference in FFL between young and old flies is linked to age-dependent differences in metabolic status and may be mediated by reduced insulin signaling.This is the publisher’s final pdf. The published article is copyrighted by the author(s) and published by John Wiley & Sons, Ltd. on behalf of the Anatomical Society. The published article can be found at: http://onlinelibrary.wiley.com/journal/10.1111/%28ISSN%291474-9726
Circadian deep sequencing reveals stress-response genes that adopt robust rhythmic expression during aging
Disruption of the circadian clock, which directs rhythmic expression of numerous output genes, accelerates aging. To enquire how the circadian system protects aging organisms, here we compare circadian transcriptomes in heads of young and old Drosophila melanogaster. The core clock and most output genes remained robustly rhythmic in old flies, while others lost rhythmicity with age, resulting in constitutive over- or under-expression. Unexpectedly, we identify a subset of genes that adopted increased or de novo rhythmicity during aging, enriched for stress-response functions. These genes, termed late-life cyclers, were also rhythmically induced in young flies by constant exposure to exogenous oxidative stress, and this upregulation is CLOCK-dependent. We also identify age-onset rhythmicity in several putative primary piRNA transcripts overlapping antisense transposons. Our results suggest that, as organisms age, the circadian system shifts greater regulatory priority to the mitigation of accumulating cellular stress
Lactate dehydrogenase expression modulates longevity and neurodegeneration in Drosophila melanogaster
Lactate dehydrogenase (LDH) catalyzes the conversion of glycolysis-derived pyruvate to lactate. Lactate has been shown to play key roles in brain energetics and memory formation. However, lactate levels are elevated in aging and Alzheimer\u27s disease patients, and it is not clear whether lactate plays protective or detrimental roles in these contexts. Here we show that Ldh transcript levels are elevated and cycle with diurnal rhythm in the heads of aged flies and this is associated with increased LDH protein, enzyme activity, and lactate concentrations. To understand the biological significance of increased Ldh gene expression, we genetically manipulated Ldh levels in adult neurons or glia. Overexpression of Ldh in both cell types caused a significant reduction in lifespan whereas Ldh down-regulation resulted in lifespan extension. Moreover, pan-neuronal overexpression of Ldh disrupted circadian locomotor activity rhythms and significantly increased brain neurodegeneration. In contrast, reduction of Ldh in neurons delayed age-dependent neurodegeneration. Thus, our unbiased genetic approach identified Ldh and lactate as potential modulators of aging and longevity in flies
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Manipulations of Amyloid Precursor Protein Cleavage Disrupt the Circadian Clock in Aging Drosophila
Alzheimer's disease (AD) is a neurodegenerative disease characterized by severe cognitive deterioration. While causes of AD pathology are debated, a large body of evidence suggests that increased cleavage of Amyloid Precursor Protein (APP) producing the neurotoxic Amyloid-β (Aβ) peptide plays a fundamental role in AD pathogenesis. One of the detrimental behavioral symptoms commonly associated with AD is the fragmentation of sleep-activity cycles with increased nighttime activity and daytime naps in humans. Sleep-activity cycles, as well as physiological and cellular rhythms, which may be important for neuronal homeostasis, are generated by a molecular system known as the circadian clock. Links between AD and the circadian system are increasingly evident but not well understood. Here we examined whether genetic manipulations of APP-like (APPL) protein cleavage in Drosophila melanogaster affect rest-activity rhythms and core circadian clock function in this model organism. We show that the increased β-cleavage of endogenous APPL by the β-secretase (dBACE) severely disrupts circadian behavior and leads to reduced expression of clock protein PER in central clock neurons of aging flies. Our data suggest that behavioral rhythm disruption is not a product of APPL-derived Aβ production but rather may be caused by a mechanism common to both α and β-cleavage pathways. Specifically, we show that increased production of the endogenous Drosophila Amyloid Intracellular Domain (dAICD) caused disruption of circadian rest-activity rhythms, while flies overexpressing endogenous APPL maintained stronger circadian rhythms during aging. In summary, our study offers a novel entry point toward understanding the mechanism of circadian rhythm disruption in Alzheimer's disease.Keywords: period gene, Amyloid precursor protein, Amyloid intracellular domain, Drosophila, Alzheimer's disease, Circadian rhythms, BAC
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Relationships between the Circadian System and Alzheimer’s Disease-Like Symptoms in Drosophila
Circadian clocks coordinate physiological, neurological, and behavioral functions into circa 24 hour rhythms, and the molecular mechanisms underlying circadian clock oscillations are conserved from Drosophila to humans. Clock oscillations and clock-controlled rhythms are known to dampen during aging; additionally, genetic or environmental clock disruption leads to accelerated aging and increased susceptibility to age-related pathologies. Neurodegenerative diseases, such as Alzheimer’s disease (AD), are associated with a decay of circadian rhythms, but it is not clear whether circadian disruption accelerates neuronal and motor decline associated with these diseases. To address this question, we utilized transgenic Drosophila expressing various Amyloid-β (Aβ) peptides, which are prone to form aggregates characteristic of AD pathology in humans. We compared development of AD-like symptoms in adult flies expressing Aβ peptides in the wild type background and in flies with clocks disrupted via a null mutation in the clock gene period (per[superscript 01]). No significant differences were observed in longevity, climbing ability and brain neurodegeneration levels between control and clock-deficient flies, suggesting that loss of clock function does not exacerbate pathogenicity caused by human-derived Aβ peptides in flies. However, AD-like pathologies affected the circadian system in aging flies. We report that rest/activity rhythms were impaired in an age-dependent manner. Flies expressing the highly pathogenic arctic Aβ peptide showed a dramatic degradation of these rhythms in tune with their reduced longevity and impaired climbing ability. At the same time, the central pacemaker remained intact in these flies providing evidence that expression of Aβ peptides causes rhythm degradation downstream from the central clock mechanism
RNA interference in Lepidoptera: an overview of successful and unsuccessful studies and implications for experimental design
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RNA interference in Lepidoptera: An overview of successful and unsuccessful studies and implications for experimental design
Age-Related Changes in the Expression of the Circadian Clock Protein PERIOD in Drosophila Glial Cells
Circadian clocks consist of molecular negative feedback loops that coordinate physiological, neurological, and behavioral variables into “circa” 24-h rhythms. Rhythms in behavioral and other circadian outputs tend to weaken during aging, as evident in progressive disruptions of sleep-wake cycles in aging organisms. However, less is known about the molecular changes in the expression of clock genes and proteins that may lead to the weakening of circadian outputs. Western blot studies have demonstrated that the expression of the core clock protein PERIOD (PER) declines in the heads of aged Drosophila melanogaster flies. This age-related decline in PER does not occur in the central pacemaker neurons but has been demonstrated so far in retinal photoreceptors. Besides photoreceptors, clock proteins are also expressed in fly glia, which play important roles in neuronal homeostasis and are further categorized into subtypes based on morphology and function. While previous studies of mammalian glial cells have demonstrated the presence of functional clocks in astrocytes and microglia, it is not known which glial cell types in Drosophila express clock proteins and how their expression may change in aged individuals. Here, we conducted immunocytochemistry experiments to identify which glial subtypes express PER protein suggestive of functional circadian clocks. Glial cell subtypes that showed night-time accumulation and day-time absence in PER consistent with oscillations reported in the pacemaker neurons were selected to compare the level of PER protein between young and old flies. Our data demonstrate that some glial subtypes show rhythmic PER expression and the relative PER levels become dampened with advanced age. Identification of glial cell types that display age-related dampening of PER levels may help to understand the cellular changes that contribute to the loss of homeostasis in the aging brain
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