Caenorhabditis elegans as Model System in Pharmacology and Toxicology: Effects of Flavonoids on Redox-Sensitive Signalling Pathways and Ageing

Flavonoids are secondary plant compounds that mediate diverse biological activities, for example, by scavenging free radicals and modulating intracellular signalling pathways. It has been shown in various studies that distinct flavonoid compounds enhance stress resistance and even prolong the life span of organisms. In the last years the model organism C. elegans has gained increasing importance in pharmacological and toxicological sciences due to the availability of various genetically modified nematode strains, the simplicity of modulating genes by RNAi, and the relatively short life span. Several studies have been performed demonstrating that secondary plant compounds influence ageing, stress resistance, and distinct signalling pathways in the nematode. Here we present an overview of the modulating effects of different flavonoids on oxidative stress, redox-sensitive signalling pathways, and life span in C. elegans introducing the usability of this model system for pharmacological and toxicological research

C. elegans VANG-1 Modulates Life Span via Insulin/IGF-1-Like Signaling

The planar cell polarity (PCP) pathway is highly conserved from Drosophila to humans and a PCP-like pathway has recently been described in the nematode Caenorhabditis elegans. The developmental function of this pathway is to coordinate the orientation of cells or structures within the plane of an epithelium or to organize cell-cell intercalation required for correct morphogenesis. Here, we describe a novel role of VANG-1, the only C. elegans ortholog of the conserved PCP component Strabismus/Van Gogh. We show that two alleles of vang-1 and depletion of the protein by RNAi cause an increase of mean life span up to 40%. Consistent with the longevity phenotype vang-1 animals also show enhanced resistance to thermal- and oxidative stress and decreased lipofuscin accumulation. In addition, vang-1 mutants show defects like reduced brood size, decreased ovulation rate and prolonged reproductive span, which are also related to gerontogenes. The germline, but not the intestine or neurons, seems to be the primary site of vang-1 function. Life span extension in vang-1 mutants depends on the insulin/IGF-1-like receptor DAF-2 and DAF-16/FoxO transcription factor. RNAi against the phase II detoxification transcription factor SKN-1/Nrf2 also reduced vang-1 life span that might be explained by gradual inhibition of insulin/IGF-1-like signaling in vang-1. This is the first time that a key player of the PCP pathway is shown to be involved in the insulin/IGF-1-like signaling dependent modulation of life span in C. elegans

Myricetin-Mediated Lifespan Extension in Caenorhabditis elegans Is Modulated by DAF-16

Myricetin is a naturally occurring flavonol found in many plant based food sources. It increases the lifespan of Caenorhabditis elegans, but the molecular mechanisms are not yet fully understood. We have investigated the impact of this flavonoid on the transcription factors DAF-16 (C. elegans FoxO homologue) and SKN-1 (Nrf2 homologue), which have crucial functions in the regulation of ageing. Myricetin is rapidly assimilated by the nematode, causes a nuclear translocation of DAF-16 but not of SKN-1, and finally prolongs the mean adult lifespan of C. elegans by 32.9%. The lifespan prolongation was associated with a decrease in the accumulation of reactive oxygen species (ROS) detected by DCF. Myricetin also decreases the formation of lipofuscin, a pigment consisting of highly oxidized and cross-linked proteins that is considered as a biomarker of ageing in diverse species. The lifespan extension was completely abolished in a daf-16 loss-of-function mutant strain (CF1038). Consistently with this result, myricetin was also not able to diminish stress-induced ROS accumulation in the mutant. These results strongly indicate that the pro-longevity effect of myricetin is dependent on DAF-16 and not on direct anti-oxidative effects of the flavonoid

Caenorhabditis elegans as Model System in Pharmacology and Toxicology: Effects of Flavonoids on Redox-Sensitive Signalling Pathways and Ageing

Flavonoids are secondary plant compounds that mediate diverse biological activities, for example, by scavenging free radicals and modulating intracellular signalling pathways. It has been shown in various studies that distinct flavonoid compounds enhance stress resistance and even prolong the life span of organisms. In the last years the model organism C. elegans has gained increasing importance in pharmacological and toxicological sciences due to the availability of various genetically modified nematode strains, the simplicity of modulating genes by RNAi, and the relatively short life span. Several studies have been performed demonstrating that secondary plant compounds influence ageing, stress resistance, and distinct signalling pathways in the nematode. Here we present an overview of the modulating effects of different flavonoids on oxidative stress, redox-sensitive signalling pathways, and life span in C. elegans introducing the usability of this model system for pharmacological and toxicological research

Polygonum multiflorum Extract Exerts Antioxidative Effects and Increases Life Span and Stress Resistance in the Model Organism Caenorhabditis elegans via DAF-16 and SIR-2.1

Extracts of the Chinese plant Polygonum multiflorum (PME) are used for medicinal purposes as well as food supplement due to anti-aging effects. Despite of the common use of these food supplements, experimental data on physiological effects of PME and its underlying molecular mechanisms in vivo are limited. We used the model organism Caenorhabditis elegans to analyze anti-aging-effects of PME in vivo (life span, lipofuscin accumulation, oxidative stress resistance, thermal stress resistance) as well as the molecular signaling pathways involved. The effects of PME were examined in wildtype animals and mutants defective in the sirtuin-homologue SIR-2.1 (VC199) and the FOXO-homologue DAF-16 (CF1038). PME possesses antioxidative effects in vivo and increases oxidative stress resistance of the nematodes. While the accumulation of lipofuscin is only slightly decreased, PME causes a significant elongation (18.6%) of mean life span. DAF-16 is essential for the reduction of thermally induced ROS accumulation, while the resistance against paraquat-induced oxidative stress is dependent on SIR-2.1. For the extension of the life span, both DAF-16 and SIR-2.1 are needed. We demonstrate that PME exerts protective effects in C. elegans via modulation of distinct intracellular pathways

Recovery of Catapleiite and Eudialyte from Non-Magnetic Fraction of Eudialyte ore Processing of Norra Kärr Deposit

Eudialyte ores from Norra Kärr (Sweden) and Kringlerne (Greenland) are considered a potential source of rare-earth elements (REE) for the development of a sustainable REE industry outside China. Magnetic separation is successfully applicated to recover eudialyte as a magnetic fraction. In the case of the Norra Kärr deposit, up to 20% of the REE and up to 40% of the Zr are lost during mineral processing in the non-magnetic fraction. Zr and REE are associated with non-magnetic minerals such as catapleiite, low- or non-magnetic eudialyte species, and both their intergrowths. Besides zirconosilicates such as catapleiite and eudialyte, the non-magnetic fraction has valuable and already-liberated minerals such as alkali feldspars and nepheline, which should not be considered as tailings. In this investigation, a possible way to recover REE bearing zirconosilicates from the non-magnetic fraction using flotation is presented. First, a low-grade eudialyte concentrate (1.8% Zr, 0.94% REE) from ground ore was obtained using magnetic separation. The non-magnetic fraction was then treated using froth flotation, and a Zr-REE bearing product (9% Zr, 1.5% REE) was obtained as froth product. For this purpose, phosphoric acid esters were used as selective collectors for zirconosilicates at a pH between 3.5 and 4.5. The reagent regime could be proposed not only to recover Zr- and REE-bearing minerals, but also simultaneously to remove Fe, Ti, and other colored impurities from the nepheline-feldspar product and to minimize the tailings volume

TSG (2,3,5,4′-Tetrahydroxystilbene-2-O-β-D-glucoside) from the Chinese Herb Polygonum multiflorum Increases Life Span and Stress Resistance of Caenorhabditis elegans

2,3,5,4′-Tetrahydroxystilbene-2-O-β-D-glucoside (TSG) was isolated from Polygonum multiflorum, a plant which is traditionally used as an anti-ageing drug. We have analysed ageing-related effects of TSG in the model organism C. elegans in comparison to resveratrol. TSG exerted a high antioxidative capacity both in a cell-free assay and in the nematode. The antioxidative capacity was even higher compared to resveratrol. Presumably due to its antioxidative effects, treatment with TSG decreased the juglone-mediated induction of the antioxidative enzyme SOD-3; the induction of the GST-4 by juglone was diminished slightly. TSG increased the resistance of C. elegans against lethal thermal stress more prominently than resveratrol (50 μM TSG increased mean survival by 22.2%). The level of the ageing pigment lipofuscin was decreased after incubation with the compound. TSG prolongs the mean, median, and maximum adult life span of C. elegans by 23.5%, 29.4%, and 7.2%, respectively, comparable to the effects of resveratrol. TSG-mediated extension of life span was not abolished in a DAF-16 loss-of-function mutant strain showing that this ageing-related transcription factor is not involved in the effects of TSG. Our data show that TSG possesses a potent antioxidative capacity, enhances the stress resistance, and increases the life span of the nematode C. elegans

Myricetin-Mediated Lifespan Extension in Caenorhabditis elegans Is Modulated by DAF-16

Abstract: Myricetin is a naturally occurring flavonol found in many plant based food sources. It increases the lifespan of Caenorhabditis elegans, but the molecular mechanisms are not yet fully understood. We have investigated the impact of this flavonoid on the transcription factors DAF-16 (C. elegans FoxO homologue) and SKN-1 (Nrf2 homologue), which have crucial functions in the regulation of ageing. Myricetin is rapidly assimilated by the nematode, causes a nuclear translocation of DAF-16 but not of SKN-1, and finally prolongs the mean adult lifespan of C. elegans by 32.9%. The lifespan prolongation was associated with a decrease in the accumulation of reactive oxygen species (ROS) detected by DCF. Myricetin also decreases the formation of lipofuscin, a pigment consisting of highly oxidized and cross-linked proteins that is considered as a biomarker of ageing in diverse species. The lifespan extension was completely abolished in a daf-16 loss-of-function mutant strain (CF1038). Consistently with this result, myricetin was als

Teil 2 - Optimierter Betrieb von E-Bussen - Ergebnisse und Bewertung des Forschungsprojekts MENDEL zur minimalen Belastung elektrischer Netze durch das Laden von Batteriebussen

Vorstellung des Forschungsprojekts MENDEL (Minimale Belastung elektrischer Netze durch Ladevorgänge von Elektrobussen) sowie dessen Ergebnisse und Beleuchtung der Smard Grid und ITS-Aspekte