Relevance of bioassay of biologically active substances (BAS) with geroprotective properties in the model of the nematode Caenorhabditis elegans in experiments in vivo

2021 ◽  
Vol 14 ◽  
Author(s):  
Lyubov S. Dyshlyuk ◽  
Anastasiya I. Dmitrieva ◽  
Margarita Yu. Drozdova ◽  
Irina S. Milentyeva ◽  
Alexander Yu. Prosekov
Keyword(s):  
Caenorhabditis Elegans ◽  
Plant Extracts ◽  
Aging Process ◽  
Model Organism ◽  
Biologically Active ◽  
Model Systems ◽  
C Elegans ◽  
Living Organisms ◽  
Active Substances

: Aging is a process global in nature. The age of living organisms contributes to the appearance of chronic diseases, which not only reduce the quality of life, but also significantly damage it. Modern medicines can successfully fight multiple diseases and prolong life. At the same time, medications have a large number of side effects. New research indicates that bioactive phytochemicals have great potential for treating even the most severe diseases and can become an alternative to medicines. Despite many studies in this area, the effects of many plant ingredients on living organisms are poorly understood. Analysis of the mechanisms through which herbal preparations influence the aging process helps to select the right active substances, determine the optimal doses to obtain the maximum positive effect. It is preferable to check the effectiveness of plant extracts and biologically active components with geroprotective properties in vivo. For these purposes, live model systems such as Rattus rattus, Mus musculus, Drosophila melanogaster, and Caenorhabditis elegans are used. These models help to comprehensively study the impact of the developed new drugs on the aging process. The model organism C. elegans is gaining increasing popularity in these studies because of its many advantages. This review article discusses the advantages of the nematode C. elegans as a model organism for studying the processes associated with aging. The influence of various BAS and plant extracts on the increase in the life span of the nematode, on the increase in its stress resistance and on other markers of aging is also considered. The review showed that the nematode C. elegans has a number of advantages over other organisms and is a promising model system for studying the geroprotective properties of BAS.

scholarly journals In vivo analysis of FANCD2 recruitment at meiotic DNA breaks in Caenorhabditis elegans

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Marcello Germoglio ◽  
Anna Valenti ◽  
Ines Gallo ◽  
Chiara Forenza ◽  
Pamela Santonicola ◽  
...  
Keyword(s):  
Dna Repair ◽  
Caenorhabditis Elegans ◽  
Genome Stability ◽  
Genetic Interaction ◽  
Model Systems ◽  
Dna Breaks ◽  
Strand Breaks ◽  
C Elegans ◽  
In Vivo Analysis

AbstractFanconi Anemia is a rare genetic disease associated with DNA repair defects, congenital abnormalities and infertility. Most of FA pathway is evolutionary conserved, allowing dissection and mechanistic studies in simpler model systems such as Caenorhabditis elegans. In the present study, we employed C. elegans to better understand the role of FA group D2 (FANCD2) protein in vivo, a key player in promoting genome stability. We report that localization of FCD-2/FANCD2 is dynamic during meiotic prophase I and requires its heterodimeric partner FNCI-1/FANCI. Strikingly, we found that FCD-2 recruitment depends on SPO-11-induced double-strand breaks (DSBs) but not RAD-51-mediated strand invasion. Furthermore, exposure to DNA damage-inducing agents boosts FCD-2 recruitment on the chromatin. Finally, analysis of genetic interaction between FCD-2 and BRC-1 (the C. elegans orthologue of mammalian BRCA1) supports a role for these proteins in different DSB repair pathways. Collectively, we showed a direct involvement of FCD-2 at DSBs and speculate on its function in driving meiotic DNA repair.

scholarly journals A fast and reliable method for monitoring genomic instability in the model organism Caenorhabditis elegans

2021 ◽  
Author(s):  
Merle Marie Nicolai ◽  
Barbara Witt ◽  
Andrea Hartwig ◽  
Tanja Schwerdtle ◽  
Julia Bornhorst
Keyword(s):  
Caenorhabditis Elegans ◽  
Animal Experiments ◽  
Model Organism ◽  
Animal Testing ◽  
C Elegans ◽  
Testing Strategies ◽  
Genotoxic Agents ◽  
Genotoxicity Testing

AbstractThe identification of genotoxic agents and their potential for genotoxic alterations in an organism is crucial for risk assessment and approval procedures of the chemical and pharmaceutical industry. Classically, testing strategies for DNA or chromosomal damage focus on in vitro and in vivo (mainly rodent) investigations. In cell culture systems, the alkaline unwinding (AU) assay is one of the well-established methods for detecting the percentage of double-stranded DNA (dsDNA). By establishing a reliable lysis protocol, and further optimization of the AU assay for the model organism Caenorhabditis elegans (C. elegans), we provided a new tool for genotoxicity testing in the niche between in vitro and rodent experiments. The method is intended to complement existing testing strategies by a multicellular organism, which allows higher predictability of genotoxic potential compared to in vitro cell line or bacterial investigations, before utilizing in vivo (rodent) investigations. This also allows working within the 3R concept (reduction, refinement, and replacement of animal experiments), by reducing and possibly replacing animal testing. Validation with known genotoxic agents (bleomycin (BLM) and tert-butyl hydroperoxide (tBOOH)) proved the method to be meaningful, reproducible, and feasible for high-throughput genotoxicity testing, and especially preliminary screening.

scholarly journals Detecting changes in the Caenorhabditis elegans intestinal environment using an engineered bacterial biosensor

2019 ◽  
Author(s):  
Jack W. Rutter ◽  
Tanel Ozdemir ◽  
Leonor M. Quintaneiro ◽  
Geraint Thomas ◽  
Filipe Cabreiro ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Rational Design ◽  
Model Organism ◽  
Bacterial Biosensor ◽  
Intestinal Environment ◽  
C Elegans ◽  
Ideal Candidate ◽  
Diagnostic Applications

AbstractCaenorhabditis elegans has become a key model organism within biology. In particular, the transparent gut, rapid growing time and ability to create a defined gut microbiota make it an ideal candidate organism for understanding and engineering the host microbiota. Here we present the development of an experimental model which can be used to characterise whole-cell bacterial biosensors in vivo. A dual-plasmid sensor system responding to isopropyl β-D-1-thiogalactopyranoside was developed and fully characterised in vitro. Subsequently, we show the sensor was capable of detecting and reporting on changes in the intestinal environment of C. elegans after introducing exogenous inducer into the environment. The protocols presented here may be used for aiding the rational design of engineered bacterial circuits, primarily for diagnostic applications. In addition, the model system may serve to reduce the use of current animal models and aid in the exploration of complex questions within general nematode and host-microbe biology.

scholarly journals Caenorhabditis elegans: A Useful Model for Studying Metabolic Disorders in Which Oxidative Stress Is a Contributing Factor

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Elizabeth Moreno-Arriola ◽  
Noemí Cárdenas-Rodríguez ◽  
Elvia Coballase-Urrutia ◽  
José Pedraza-Chaverri ◽  
Liliana Carmona-Aparicio ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Caenorhabditis Elegans ◽  
Metabolic Disorders ◽  
Molecular Mechanisms ◽  
Second Messengers ◽  
Model Organism ◽  
Human Diseases ◽  
C Elegans ◽  
Molecular Bases

Caenorhabditis elegansis a powerful model organism that is invaluable for experimental research because it can be used to recapitulate most human diseases at either the metabolic or genomic levelin vivo. This organism contains many key components related to metabolic and oxidative stress networks that could conceivably allow us to increase and integrate information to understand the causes and mechanisms of complex diseases. Oxidative stress is an etiological factor that influences numerous human diseases, including diabetes.C. elegansdisplays remarkably similar molecular bases and cellular pathways to those of mammals. Defects in the insulin/insulin-like growth factor-1 signaling pathway or increased ROS levels induce the conserved phase II detoxification response via the SKN-1 pathway to fight against oxidative stress. However, it is noteworthy that, aside from the detrimental effects of ROS, they have been proposed as second messengers that trigger the mitohormetic response to attenuate the adverse effects of oxidative stress. Herein, we briefly describe the importance ofC. elegansas an experimental model system for studying metabolic disorders related to oxidative stress and the molecular mechanisms that underlie their pathophysiology.

Caenorhabditis elegans: A promising contrivance to study neurotoxicity and oxidative stress

2021 ◽  
Vol 16 (10) ◽  
pp. 198-206
Author(s):  
Kiran Singh ◽  
Shweta Yadav
Keyword(s):  
Oxidative Stress ◽  
Caenorhabditis Elegans ◽  
Genetic Manipulation ◽  
Model Organism ◽  
Mechanisms Of Toxicity ◽  
C Elegans ◽  
Toxicological Studies ◽  
And Oxidative Stress

Owing to ubiquitous distribution, high abundances and ecological relevance, Caenorhabditis elegans has strong potential interest as barometer of environment and human health. Ecotoxicological methods are used to evaluate the effect of various anthropogenic contaminants on the ecosystems that circumscribe both in-vivo and in-vitro toxicities to explore the pathways and mechanisms of toxicity and to set precise toxicity thresholds. The interest in C. elegans, as a model organism in toxicological studies, has increased over the past few decades. The enticement of C. elegans comes from the ease of metabolically active digestive, sensory, endocrine, neuromuscular, reproductive systems and genetic manipulation along with the ability to fluorescently label neuronal subtypes. The study reviews the competence of Caenorhabditis elegans as a potential model organism in various toxicity assays specifically neurotoxicity and oxidative stress.

scholarly journals ROS in AgingCaenorhabditis elegans: Damage or Signaling?

2012 ◽  
Vol 2012 ◽  
pp. 1-14 ◽  
Author(s):  
Patricia Back ◽  
Bart P. Braeckman ◽  
Filip Matthijssens
Keyword(s):  
Oxidative Stress ◽  
Aging Process ◽  
Model Organism ◽  
Mechanistic Explanation ◽  
Redox Status ◽  
Oxygen Species ◽  
C Elegans ◽  
Development And Aging

Many insights into the mechanisms and signaling pathways underlying aging have resulted from research on the nematodeCaenorhabditis elegans. In this paper, we discuss the recent findings that emerged using this model organism concerning the role of reactive oxygen species (ROS) in the aging process. The accrual of oxidative stress and damage has been the predominant mechanistic explanation for the process of aging for many years, but reviewing the recent studies inC. eleganscalls this theory into question. Thus, it becomes more and more evident that ROS are not merely toxic byproducts of the oxidative metabolism. Rather it seems more likely that tightly controlled concentrations of ROS and fluctuations in redox potential are important mediators of signaling processes. We therefore discuss some theories that explain how redox signaling may be involved in aging and provide some examples of ROS functions and signaling inC. elegansmetabolism. To understand the role of ROS and the redox status in physiology, stress response, development, and aging, there is a rising need for accurate and reversiblein vivodetection. Therefore, we comment on some methods of ROS and redox detection with emphasis on the implementation of genetically encoded biosensors inC. elegans.

scholarly journals Identification, functional expression and enzymic analysis of two distinct CaaX proteases from Caenorhabditis elegans

2003 ◽  
Vol 370 (3) ◽  
pp. 1047-1054 ◽  
Author(s):  
Juan CADIÑANOS ◽  
Walter K. SCHMIDT ◽  
Antonio FUEYO ◽  
Ignacio VARELA ◽  
Carlos LÓPEZ-OTÍN ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Model Organism ◽  
Functional Expression ◽  
Cysteine Residue ◽  
C Elegans ◽  
Ras Gtpases ◽  
Acid Protein ◽  
Bona Fide

Post-translational processing of proteins such as the Ras GTPases, which contain a C-terminal CaaX motif (where C stands for cysteine, a for aliphatic and X is one of several amino acids), includes prenylation, proteolytic removal of the C-terminal tripeptide and carboxy-methylation of the isoprenyl-cysteine residue. In the present study, we report the presence of two distinct CaaX-proteolytic activities in membrane extracts from Caenorhabditis elegans, which are sensitive to EDTA and Tos-Phe-CH2Cl (tosylphenylalanylchloromethane; ‘TPCK') respectively. A protein similar to the mammalian and yeast farnesylated-proteins converting enzyme-1 (FACE-1)/Ste24p CaaX metalloprotease, encoded by a hypothetical gene (CeFACE-1/C04F12.10) found in C. elegans chromosome I, probably accounts for the EDTA-sensitive activity. An orthologue of FACE-2/Rce1p, the enzyme responsible for the proteolytic maturation of Ras oncoproteins and other prenylated substrates, probably accounts for the Tos-Phe-CH2Cl-sensitive activity, even though the gene for FACE-2/Rce1 has not been previously identified in this model organism. We have identified a previously overlooked gene in C. elegans chromosome V, which codes for a 266-amino-acid protein (CeFACE-2) with 30% sequence identity to human FACE-2/Rce1. We show that both CeFACE-1 and CeFACE-2 have the ability to promote production of the farnesylated yeast pheromone a-factor in vivo and to cleave a farnesylated peptide in vitro. These results indicate that CeFACE-1 and CeFACE-2 are bona fide CaaX proteases and support the evolutionary conservation of this proteolytic system in eukaryotes.

scholarly journals HeALTH: An Automated Platform for Long-term Longitudinal Studies of Whole Organisms under Precise Environmental Control

2019 ◽  
Author(s):  
Kim N. Le ◽  
Mei Zhan ◽  
Yongmin Cho ◽  
Jason Wan ◽  
Dhaval S. Patel ◽  
...  
Keyword(s):  
Aging Process ◽  
Large Scale ◽  
Environmental Control ◽  
Model Organism ◽  
Model Systems ◽  
Aging Research ◽  
C Elegans ◽  
Environmental Perturbations ◽  
Automated Platform

ABSTRACTHealth and longevity in all organisms are strongly influenced by the environment. To fully understand how environmental factors interact with genetic and stochastic factors to modulate the aging process, it is crucial to precisely control environmental conditions for long-term studies. In the commonly used model organism Caenorhabditis elegans, existing assays for healthspan and lifespan have inherent limitations, making it difficult to perform large-scale, longitudinal aging studies under precise environmental control. To address this constraint, we developed the Health and Lifespan Testing Hub (HeALTH), an automated, microfluidic-based system for robust, long-term, longitudinal behavioral monitoring. Our system provides spatiotemporal environmental control. We demonstrate health and lifespan studies under a variety of genetic and environmental perturbations while observing how individuality plays a role in the aging process. This system is generalizable beyond aging research for C. elegans, particularly for short- or long-term behavioral assays, and is also possible to be adapted for other model systems.

scholarly journals The Role of Ca2+ Signaling in Aging and Neurodegeneration: Insights from Caenorhabditis elegans Models

Cells ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 204 ◽  
Author(s):  
Javier Alvarez ◽  
Pilar Alvarez-Illera ◽  
Paloma García-Casas ◽  
Rosalba I. Fonteriz ◽  
Mayte Montero
Keyword(s):  
Caenorhabditis Elegans ◽  
Model Organism ◽  
Ample Evidence ◽  
C Elegans ◽  
Physiological Processes ◽  
Human Proteins ◽  
Β Amyloid ◽  
Key Events

Ca2+ is a ubiquitous second messenger that plays an essential role in physiological processes such as muscle contraction, neuronal secretion, and cell proliferation or differentiation. There is ample evidence that the dysregulation of Ca2+ signaling is one of the key events in the development of neurodegenerative processes, an idea called the “calcium hypothesis” of neurodegeneration. Caenorhabditis elegans (C. elegans) is a very good model for the study of aging and neurodegeneration. In fact, many of the signaling pathways involved in longevity were first discovered in this nematode, and many models of neurodegenerative diseases have also been developed therein, either through mutations in the worm genome or by expressing human proteins involved in neurodegeneration (β-amyloid, α-synuclein, polyglutamine, or others) in defined worm tissues. The worm is completely transparent throughout its whole life, which makes it possible to carry out Ca2+ dynamics studies in vivo at any time, by expressing Ca2+ fluorescent probes in defined worm tissues, and even in specific organelles such as mitochondria. This review will summarize the evidence obtained using this model organism to understand the role of Ca2+ signaling in aging and neurodegeneration.

scholarly journals Promoters of the dhs-21 gene encoding dicarbonyl/l-xylulose reductase in Caenorhabditis elegans

2018 ◽  
Vol 15 (2) ◽  
pp. 359-365
Author(s):  
Lê Thọ Sơn ◽  
Joohong Ahnn ◽  
Jeong Hoon Cho ◽  
Nguyễn Huy Hoàng
Keyword(s):  
Caenorhabditis Elegans ◽  
Model Organism ◽  
Biological Research ◽  
Loss Of Function ◽  
Wild Type ◽  
C Elegans ◽  
Larval Stages ◽  
Vital Functions

Dicarbonyl/L-xylulose (DCXR) was identified as a dehydrogenase. This type of enzyme was presented in various forms of lives including bacteria, fungi, plants and animals. Generally, it converts L-xylulose to xylitol in the presence of either cofactor NADH or NADPH in vitro. Previous studies reported the biochemistry properties and crystal structure but largely uncovered biological roles of DCXRs. It was impossible to dissect the functions in mice or human cells that had many DCXR homologs in their genomes. Interestingly, the wild-type Caenorhabditis elegans, a well-known model organism in biological research, has only nuclear genomic dhs-21 that encodes a unique homologous DCXR. Thus Ce.dhs-21 and the host C. elegans were relevant for investigation of the physiologically-vital functions of the DCXR. This research aimed to the expression of dhs-21 in vivo. We defined three promoters , manipulated three relative reporter-constructs that conjugated the dhs-21 gene and Green Flouresent Protein (known as GFP) one. The construct vectors were transferred into wild-type C. elegans N2 and as well as the hermaphroditic loss of function dhs-21(jh129) by microinjection. In the results, we found that the expression pattern of dhs-21 under the only p2-promoter construct was stable and similar to immunogold Electric Microscopy (EM) images. The dhs-21 gene was expressed in both sexes of at all larval stages till the deaths of worms. DHS-21 was expressed in the cytosol of the intestinal, gonad sheath and uterous seam cell (utse).

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