scholarly journals Chronobiotics KL001 and KS15 Extend Lifespan and Modify Circadian Rhythms of Drosophila melanogaster

2021 ◽  
Author(s):  
Ilya Solovev ◽  
Mikhail Shaposhnikov ◽  
Alexey Moskalev
Keyword(s):  
Drosophila Melanogaster ◽  
Locomotor Activity ◽  
Circadian Rhythms ◽  
Molecular Mechanisms ◽  
Fat Body ◽  
Young Male ◽  
Constant Darkness ◽  
Starvation Resistance ◽  
Positive Effects ◽  
Median Lifespan

Chronobiotics is a group of drugs utilized to modify circadian rhythms targeting clock-associated molecular mechanisms. The circadian clock is known as a controller of numerous processes standing behind aging. Hypothesis: KL001 and KS15 targeting CRY, affect lifespan, locomotor activity and circadian rhythm of Drosophila melanogaster. We observed a slight (2%, p<0.001) geroprotective effect on median lifespan (5 µM solution of KL001 in 0.1% DMSO) and a 14% increase in maximum lifespan in the same group. KS15 10 µM solution extended males’ median lifespan by 8% (p <0.05). The statistically significant positive effects of KL001 and KS15 on lifespan were not observed in female flies. KL001 5 µM solution improved locomotor activity in young male imagos (p<0.05) and elevated morning activity peak in aged imagos and modified robustness of circadian rhythms, leaving the period intact. KS15 10 µM solution decreased the locomotor activity in constant darkness and minimized the number of rhythmic flies. KL001 5 µM solution improved by 9% the mean starvation resistance in male flies (p<0.01), while median resistance was elevated by 50% (p<0.0001). This phenomenon may suggest the presence of the mechanism associated with improvement of fat body glucose depos’ utilization in starvation conditions which is activated by dCRY binding KL001.

scholarly journals Chronobiotics KL001 and KS15 Extend Lifespan and Modify Circadian Rhythms of Drosophila melanogaster

2021 ◽  
Vol 3 (3) ◽  
pp. 429-441
Author(s):  
Ilya A. Solovev ◽  
Mikhail V. Shaposhnikov ◽  
Alexey A. Moskalev
Keyword(s):  
Drosophila Melanogaster ◽  
Locomotor Activity ◽  
Circadian Rhythms ◽  
Molecular Mechanisms ◽  
Fat Body ◽  
Young Male ◽  
Constant Darkness ◽  
Starvation Resistance ◽  
Positive Effects ◽  
Median Lifespan

Chronobiotics are a group of drugs, which are utilized to modify circadian rhythms targeting clock-associated molecular mechanisms. The circadian clock is known as a controller of numerous processes in connection with aging. Hypothesis: KL001 and KS15 targeting CRY, affect lifespan, locomotor activity and circadian rhythm of Drosophila melanogaster. We observed a slight (2%, p < 0.001) geroprotective effect on median lifespan (5 µM solution of KL001 in 0.1% DMSO) and a 14% increase in maximum lifespan in the same group. KS15 10 µM solution extended males’ median lifespan by 8% (p < 0.05). The statistically significant positive effects of KL001 and KS15 on lifespan were not observed in female flies. KL001 5 µM solution improved locomotor activity in young male imagoes (p < 0.05), elevated morning activity peak in aged imagoes and modified robustness of their circadian rhythms, leaving the period intact. KS15 10 µM solution decreased the locomotor activity in constant darkness and minimized the number of rhythmic flies. KL001 5 µM solution improved by 9% the mean starvation resistance in male flies (p < 0.01), while median resistance was elevated by 50% (p < 0.0001). This phenomenon may suggest the presence of the mechanism associated with improvement of fat body glucose depos’ utilization in starvation conditions which is activated by dCRY binding KL001.

MUSHROOM BODY INFLUENCE ON LOCOMOTOR ACTIVITY AND CIRCADIAN RHYTHMS IN DROSOPHILA MELANOGASTER

2002 ◽  
Vol 16 (2) ◽  
pp. 73-109 ◽  
Author(s):  
CHARLOTTE HELFRICH-FÖRSTER ◽  
JÖRG WULF ◽  
J. STEVEN DE BELLE
Keyword(s):  
Drosophila Melanogaster ◽  
Locomotor Activity ◽  
Circadian Rhythms ◽  
Mushroom Body

scholarly journals Regulation of Fat Cell Mass by Insulin in Drosophila melanogaster

2009 ◽  
Vol 29 (24) ◽  
pp. 6341-6352 ◽  
Author(s):  
Justin R. DiAngelo ◽  
Morris J. Birnbaum
Keyword(s):  
Drosophila Melanogaster ◽  
Insulin Signaling ◽  
Fat Body ◽  
Glycogen Synthase ◽  
Cell Mass ◽  
Fruit Fly ◽  
Cell Number ◽  
Fat Cell ◽  
Positive Effects ◽  
Adipocyte Cell

ABSTRACT A phylogenetically conserved response to nutritional abundance is an increase in insulin signaling, which initiates a set of biological responses dependent on the species. Consequences of augmented insulin signaling include developmental progression, cell and organ growth, and the storage of carbohydrates and lipids. Here, we address the evolutionary origins of insulin's positive effects on anabolic lipid metabolism by selectively modulating insulin signaling in the fat body of the fruit fly, Drosophila melanogaster. Analogous to the actions of insulin in higher vertebrates, those in Drosophila include expansion of the insect fat cell mass both by increasing the adipocyte number and by promoting lipid accumulation. The ability of insulin to accomplish the former depends on its capacity to bring about phosphorylation and inhibition of the transcription factor Drosophila FOXO (dFOXO) and the serine/threonine protein kinase shaggy, the fly ortholog of glycogen synthase kinase 3 (GSK3). Increasing the amount of triglyceride per cell also depends on the phosphorylation of shaggy but is independent of dFOXO. Thus, the findings of this study provide evidence that the control of fat mass by insulin is a conserved process and place dFOXO and shaggy/GSK3 downstream of the insulin receptor in controlling adipocyte cell number and triglyceride storage, respectively.

scholarly journals Tissue-Specific Knockdown of Genes of the Argonaute Family Modulates Lifespan and Radioresistance in Drosophila Melanogaster

2021 ◽  
Author(s):  
Ekaterina N. Proshkina ◽  
Elena Yushkova ◽  
Liubov Koval ◽  
Nadezhda Zemskaya ◽  
Evgeniya Shchegoleva ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Small Rnas ◽  
Molecular Mechanisms ◽  
Fat Body ◽  
Expression Patterns ◽  
Regulation Of Gene Expression ◽  
Stress Factors ◽  
Tissue Specific ◽  
Argonaute Family ◽  
Transposon Activity

Small RNAs are essential for the coordination of many cellular processes, including the regulation of gene expression patterns, the prevention of genomic instability, and the suppression of mutagenic transposon activity. These processes determine aging, longevity, and sensitivity of cells and an organism to stress factors (particularly, ionizing radiation). The biogenesis and activity of small RNAs are provided by proteins of the Argonaute family. These proteins participate in the processing of small RNA precursors and the formation of an RNA-induced silencing complex. However, the role of Argonaute proteins in the regulation of lifespan and radioresistance remains poorly explored. We studied the effect of knockdown of Argonaute genes (AGO1, AGO2, AGO3, piwi) in various tissues on the Drosophila melanogaster lifespan and survival after the &gamma;-irradiation at a dose of 700 Gy. In most cases, these parameters were reduced or did not change significantly in flies with tissue-specific RNA interference. Surprisingly, piwi knockdown in both the fat body and the nervous system caused a lifespan increase. But changes in radioresistance depended on the tissue in which the gene was knocked out. In addition, analysis of changes in retrotransposon levels and expression of stress response genes allowed us to determine associated molecular mechanisms.

scholarly journals The lysine demethylase dKDM2 is non-essential for viability, but regulates circadian rhythms in Drosophila

2018 ◽  
Author(s):  
Yani Zheng ◽  
Yongbo Xue ◽  
Xingjie Ren ◽  
Xiao-Jun Xie ◽  
Mengmeng Liu ◽  
...  
Keyword(s):  
Circadian Rhythms ◽  
Histone Methylation ◽  
Molecular Mechanisms ◽  
Abnormal Development ◽  
Null Alleles ◽  
Constant Darkness ◽  
Post Translational Modification ◽  
Developmental Defects ◽  
Chromatin Dynamics

AbstractPost-translational modification of histones, such as histone methylation controlled by specific methyltransferases and demethylases, play critical roles in modulating chromatin dynamics and transcription in eukaryotes. Misregulation of histone methylation can lead to aberrant gene expression, thereby contributing to abnormal development and diseases such as cancer. As such, the mammalian lysine-specific demethylase 2 (KDM2) homologs, KDM2A and KDM2B, are either oncogenic or tumor suppressive, depending on specific pathological contexts. However, the role of KDM2 proteins during development in the whole organisms remains poorly understood. Unlike vertebrates, Drosophila has only one KDM2 homolog (dKDM2), but its functions in vivo remain elusive due to the complexities of the existing mutant alleles. To address this problem, we have generated two dKdm2 null alleles using the CRISPR/Cas9 technique. These dKdm2 homozygous mutants are fully viable and fertile, with no developmental defects observed under laboratory conditions. However, the dKdm2 null mutant adults display defects in circadian rhythms. Most of the dKdm2 mutants become arrhythmic under constant darkness, while the circadian period of the rhythmic mutant flies is approximately one hour shorter than the control. Interestingly, opposite defects are observed when dKDM2 is overexpressed in circadian pacemaker neurons. Taken together, these results demonstrate that dKdm2 is not essential for viability; instead, dKDM2 protein plays important roles in regulating circadian rhythms in Drosophila. Further analyses of the molecular mechanisms of how dKDM2 and its orthologs in vertebrates regulate circadian rhythms will advance our understanding of the epigenetic regulations of circadian clocks.

scholarly journals Short Neuropeptide F regulates the starvation mediated enhanced locomotor Activity in Drosophila

2019 ◽  
Author(s):  
Anna Geo ◽  
Himani Pathak ◽  
Anamika Elizabeth Kujur ◽  
Sreesha R Sudhakar ◽  
Nisha N Kannan
Keyword(s):  
Locomotor Activity ◽  
Circadian Clock ◽  
Internal Energy ◽  
Nutrient Availability ◽  
Activity Rhythm ◽  
Transcript Level ◽  
Constant Darkness ◽  
Starvation Resistance ◽  
Neuropeptide F

AbstractThe circadian clock regulates various behavioral, metabolic and physiological processes to occur at the most suitable time of the day. Internal energy stores and nutrient availability modulates the most apparent circadian clock mediated locmotor activity rhythm in Drosophila. Although previous studies unraveled the role of circadian clock in metabolism and activity rest rhythm, the precise pathway through which the circadian neuropeptidergic signaling regulates internal energy storage and the starvation-mediated increase in activity resembling foraging remains largely unclear. This study was aimed to elucidate the role of circadian neuropeptide, short neuropeptide F (sNPF) in triglyceride metabolism, starvation resistance and starvation-mediated increased locomotor activity in Drosophila. The results showed that snpf transcripts exhibits significant rhythmicity in wild type flies under 12:12 hour light-dark cycles (LD) and constant darkness (DD) whereas snpf transcript level in period null flies did not exhibit any significant rhythmicity under LD. Knockdown of sNPF in circadian clock neurons reduced the triglyceride level, starvation resistance and increased the starvation-mediated hyperactivity response after 24 hour of starvation. Further studies showed that knock down of sNPF receptors (sNPFR) expressed in insulin producing cells (IPC) increased the starvation resistance and reduced starvation-induced hyperactivity response after 24 hour of starvation. Collectively, our results suggest that transcriptional oscillation of snpf mRNA is endogenously controlled by the circadian clock and elucidate the role of sNPF in modulating locomotor activity in accordance with the nutrient availability in Drosophila.

scholarly journals Obesity-associated cardiac dysfunction in starvation-selected Drosophila melanogaster

2015 ◽  
Vol 309 (6) ◽  
pp. R658-R667 ◽  
Author(s):  
Christopher M. Hardy ◽  
Ryan T. Birse ◽  
Matthew J. Wolf ◽  
Lin Yu ◽  
Rolf Bodmer ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Lipid Droplets ◽  
Fat Body ◽  
Strong Relationship ◽  
Starvation Resistance ◽  
Intracellular Lipid ◽  
Genetic Changes ◽  
Heart Dysfunction ◽  
Genetic Manipulations ◽  
Fat Deposits

There is a clear link between obesity and cardiovascular disease, but the complexity of this interaction in mammals makes it difficult to study. Among the animal models used to investigate obesity-associated diseases, Drosophila melanogaster has emerged as an important platform of discovery. In the laboratory, Drosophila can be made obese through lipogenic diets, genetic manipulations, and adaptation to evolutionary stress. While dietary and genetic changes that cause obesity in flies have been demonstrated to induce heart dysfunction, there have been no reports investigating how obesity affects the heart in laboratory-evolved populations. Here, we studied replicated populations of Drosophila that had been selected for starvation resistance for over 65 generations. These populations evolved characteristics that closely resemble hallmarks of metabolic syndrome in mammals. We demonstrate that starvation-selected Drosophila have dilated hearts with impaired contractility. This phenotype appears to be correlated with large fat deposits along the dorsal cuticle, which alter the anatomical position of the heart. We demonstrate a strong relationship between fat storage and heart dysfunction, as dilation and reduced contractility can be rescued through prolonged fasting. Unlike other Drosophila obesity models, the starvation-selected lines do not exhibit excessive intracellular lipid deposition within the myocardium and rather store excess triglycerides in large lipid droplets within the fat body. Our findings provide a new model to investigate obesity-associated heart dysfunction.

scholarly journals Role of mutation of the circadian clock gene Per2 in cardiovascular circadian rhythms

2010 ◽  
Vol 298 (3) ◽  
pp. R627-R634 ◽  
Author(s):  
Ana Vukolic ◽  
Vladan Antic ◽  
Bruce N. Van Vliet ◽  
Zhihong Yang ◽  
Urs Albrecht ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Locomotor Activity ◽  
Circadian Rhythms ◽  
Circadian Clock ◽  
Mutant Mice ◽  
Constant Darkness ◽  
Wild Type ◽  
Chi Square ◽  
Dark Light

Alterations in the circadian blood pressure pattern are frequently observed in hypertension and lead to increased cardiovascular morbidity. However, there are no studies that have investigated a possible implication of the Period2 gene, a key component of the molecular circadian clock, on the circadian rhythms of blood pressure and heart rate. To address this question, we monitored blood pressure, heart rate, and locomotor activity 24 h a day by telemetry in mice carrying a mutation in the Period2 gene and in wild-type control mice. Under a standard 12:12-h light-dark cycle, mutant mice showed a mild cardiovascular phenotype with an elevated 24-h heart rate, a decreased 24-h diastolic blood pressure, and an attenuation of the dark-light difference in blood pressure and heart rate. Locomotor activity was similar in both groups and did not appear to explain the observed hemodynamic differences. When mice were placed under constant darkness during eight consecutive days, wild-type mice maintained 24-h rhythms, whereas there was an apparent progressive loss of 24-h rhythm of blood pressure, heart rate, and locomotor activity in mutant mice. However, a chi square periodogram revealed that circadian rhythms were preserved under complete absence of any light cue, but with shorter periods by ∼40 min, leading to a cumulative phase shift toward earlier times of ∼5 h and 20 min by the end of the 8th day. When heart rate, mean arterial pressure, and activity were recalculated according to the endogenous circadian periods of each individual mouse, the amplitudes of the circadian rhythms (“subjective night”-“subjective day” differences) were maintained for all variables studied. Our data show that mutation of the Period2 gene results in an attenuated dipping of blood pressure and heart rate during both light-dark cycles and constant darkness, and in shorter circadian periods during constant darkness.

Circadian activity of the white sucker, Catostomus commersoni: comparison of individual and shoaling fish

1980 ◽  
Vol 58 (8) ◽  
pp. 1399-1403 ◽  
Author(s):  
Martin Kavaliers
Keyword(s):  
Locomotor Activity ◽  
Circadian Rhythms ◽  
Social Organization ◽  
Constant Darkness ◽  
White Sucker ◽  
Circadian Period ◽  
Circadian Activity ◽  
Catostomus Commersoni ◽  
Free Running ◽  
Precise Version

Individual and shoaling white suckers, Catostomus commersoni, displayed free running circadian rhythms of locomotor activity under conditions of constant darkness and temperature. The circadian activity of shoals was different from that of single fish. The activity of single fish was rhythmic initially with a period of less than 24 h, but became arrhythmic after 15–30 days. Shoals of white suckers had a less variable circadian period that was greater than 24 h, and showed no evidence of arrhythmicity. The circadian activity of shoals is determined by its behavioural and social organization; it is not simply a more precise version of the activity of single fish.

scholarly journals Tissue-Specific Knockdown of Genes of the Argonaute Family Modulates Lifespan and Radioresistance in Drosophila melanogaster

2021 ◽  
Vol 22 (5) ◽  
pp. 2396
Author(s):  
Ekaterina Proshkina ◽  
Elena Yushkova ◽  
Liubov Koval ◽  
Nadezhda Zemskaya ◽  
Evgeniya Shchegoleva ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Small Rnas ◽  
Molecular Mechanisms ◽  
Fat Body ◽  
Expression Patterns ◽  
Regulation Of Gene Expression ◽  
Stress Factors ◽  
Γ Irradiation ◽  
Tissue Specific ◽  
Argonaute Family

Small RNAs are essential to coordinate many cellular processes, including the regulation of gene expression patterns, the prevention of genomic instability, and the suppression of the mutagenic transposon activity. These processes determine the aging, longevity, and sensitivity of cells and an organism to stress factors (particularly, ionizing radiation). The biogenesis and activity of small RNAs are provided by proteins of the Argonaute family. These proteins participate in the processing of small RNA precursors and the formation of an RNA-induced silencing complex. However, the role of Argonaute proteins in regulating lifespan and radioresistance remains poorly explored. We studied the effect of knockdown of Argonaute genes (AGO1, AGO2, AGO3, piwi) in various tissues on the Drosophila melanogaster lifespan and survival after the γ-irradiation at a dose of 700 Gy. In most cases, these parameters are reduced or did not change significantly in flies with tissue-specific RNA interference. Surprisingly, piwi knockdown in both the fat body and the nervous system causes a lifespan increase. But changes in radioresistance depend on the tissue in which the gene was knocked out. In addition, analysis of changes in retrotransposon levels and expression of stress response genes allow us to determine associated molecular mechanisms.

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