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 Automated Platform for Long-Term Culture and High-Content Phenotyping of Single C. elegans Worms

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
H. B. Atakan ◽  
R. Xiang ◽  
M. Cornaglia ◽  
L. Mouchiroud ◽  
E. Katsyuba ◽  
...  
Keyword(s):  
High Throughput ◽  
Agar Plate ◽  
Model Organism ◽  
Suitable Model ◽  
Microfluidic Chips ◽  
Long Term Culture ◽  
C Elegans ◽  
Bleaching Procedure ◽  
Automated Platform

Abstract The nematode Caenorhabditis elegans is a suitable model organism in drug screening. Traditionally worms are grown on agar plates, posing many challenges for long-term culture and phenotyping of animals under identical conditions. Microfluidics allows for ‘personalized’ phenotyping, as microfluidic chips permit collecting individual responses over worms’ full life. Here, we present a multiplexed, high-throughput, high-resolution microfluidic approach to culture C. elegans from embryo to the adult stage at single animal resolution. We allocated single embryos to growth chambers, for observing the main embryonic and post-embryonic development stages and phenotypes, while exposing worms to up to 8 different well-controlled chemical conditions. Our approach allowed eliminating bacteria aggregation and biofilm formation-related clogging issues, which enabled us performing up to 80 hours of automated single worm culture studies. Our microfluidic platform is linked with an automated phenotyping code that registers organism-associated phenotypes at high-throughput. We validated our platform with a dose-response study of the anthelmintic drug tetramisole by studying its influence through the life cycle of the nematodes. In parallel, we could observe development effects and variations in single embryo and worm viability due to the bleaching procedure that is standardly used for harvesting the embryos from a worm culture agar plate.

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 Health and longevity studies in C. elegans: the “healthy worm database” reveals strengths, weaknesses and gaps of test compound-based studies

2021 ◽  
Vol 22 (2) ◽  
pp. 215-236
Author(s):  
Nadine Saul ◽  
Steffen Möller ◽  
Francesca Cirulli ◽  
Alessandra Berry ◽  
Walter Luyten ◽  
...  
Keyword(s):  
Healthy Aging ◽  
Model Organism ◽  
Research Field ◽  
Aging Research ◽  
Genetic Manipulations ◽  
C Elegans ◽  
Starting Point ◽  
Health Related ◽  
Phenotype Measurement ◽  
Or Gene

AbstractSeveral biogerontology databases exist that focus on genetic or gene expression data linked to health as well as survival, subsequent to compound treatments or genetic manipulations in animal models. However, none of these has yet collected experimental results of compound-related health changes. Since quality of life is often regarded as more valuable than length of life, we aim to fill this gap with the “Healthy Worm Database” (http://healthy-worm-database.eu). Literature describing health-related compound studies in the aging model Caenorhabditis elegans was screened, and data for 440 compounds collected. The database considers 189 publications describing 89 different phenotypes measured in 2995 different conditions. Besides enabling a targeted search for promising compounds for further investigations, this database also offers insights into the research field of studies on healthy aging based on a frequently used model organism. Some weaknesses of C. elegans-based aging studies, like underrepresented phenotypes, especially concerning cognitive functions, as well as the convenience-based use of young worms as the starting point for compound treatment or phenotype measurement are discussed. In conclusion, the database provides an anchor for the search for compounds affecting health, with a link to public databases, and it further highlights some potential shortcomings in current aging research.

scholarly journals Long-term activity drives dendritic branch elaboration of a C. elegans sensory neuron

2019 ◽  
Author(s):  
Jesse A Cohn ◽  
Elizabeth R Cebul ◽  
Giulio Valperga ◽  
Mario de Bono ◽  
Maxwell G Heiman ◽  
...  
Keyword(s):  
Sensory Neuron ◽  
Neuronal Activity ◽  
Morphological Changes ◽  
Model Organism ◽  
Neuronal Morphology ◽  
Sensory Transduction ◽  
Central Component ◽  
C Elegans ◽  
Activity Dependent

ABSTRACTNeuronal activity often leads to alterations in gene expression and cellular architecture. The nematode Caenorhabditis elegans, owing to its compact translucent nervous system, is a powerful system in which to study conserved aspects of the development and plasticity of neuronal morphology. Here we focus on one sensory neuron in the worm, termed URX, which senses oxygen and signals tonically proportional to environmental oxygen. Previous studies have reported that URX has variable branched endings at its dendritic sensory tip. By controlling oxygen levels and analyzing mutants, we found that these branched endings grow over time as a consequence of neuronal activity. Furthermore, we observed that the branches contain microtubules, but do not appear to harbor the guanylyl cyclase GCY-35, a central component of the oxygen sensory transduction pathway. Interestingly, we found that although URX dendritic tips grow branches in response to long-term activity, the degree of branch elaboration does not correlate with oxygen sensitivity at the cellular or the behavioral level. Given the strengths of C. elegans as a model organism, URX may serve as a potent system for uncovering genes and mechanisms involved in activity-dependent morphological changes in neurons.

scholarly journals NemaLife: A structured microfluidic culture device optimized for aging studies in crawling C. elegans

2019 ◽  
Author(s):  
Mizanur Rahman ◽  
Hunter Edwards ◽  
Nikolajs Birze ◽  
Rebecca Gabrilska ◽  
Kendra P. Rumbaugh ◽  
...  
Keyword(s):  
Large Scale ◽  
The Body ◽  
Physiological Data ◽  
Aging Research ◽  
C Elegans ◽  
Age Related ◽  
Technology Platforms ◽  
Aging Studies ◽  
Pharyngeal Pumping ◽  
Culture Maintenance

AbstractCaenorhabditis elegans is a powerful animal model in aging research. Standard longevity assays on agar plates involve the tedious task of picking and transferring animals to prevent younger progeny from contaminating age-synchronized adult populations. Large-scale studies employ progeny-blocking drugs or sterile mutants to avoid progeny contamination, but such manipulations change adult physiology and alter the influence of reproduction on normal aging. Moreover, for some agar growth-based technology platforms, such as automated lifespan machines, reagents such as food or drugs cannot be readily added/removed after initiation of the study. Current microfluidic approaches are well-suited to address these limitations, but in their liquid-based environments animals swim rather than crawl, introducing swim-induced stress in the lifespan analysis. Here we report a simple microfluidic device that we call NemaLife that features: 1) an optimized micropillar arena in which animals can crawl, 2) sieve channels that separate progeny and prevent the loss of adults from the arena during culture maintenance, and 3) ports which allow rapid accessibility to feed the adult-only population and introduce reagents as needed. Culture maintenance and liquid manipulation are performed with simple hand-held syringes to facilitate integration of our technology into general laboratory protocols. Additionally, device geometry and feeding protocols were designed to emulate the body gait, locomotion, and lifespan of animals reared on agar. We validated our approach with longevity analyses of classical aging mutants (daf-2, age-1, eat-2, and daf-16) and animals subjected to RNAi knockdown of age-related genes (age-1 and daf-16). We also showed that healthspan measures such as pharyngeal pumping and tap-induced stimulated reversals can be scored across the lifespan. Overall, the capacity to generate reliable lifespan and physiological data from the NemaLife chip underscores the potential of this device to accelerate healthspan and lifespan investigations in C. elegans.

scholarly journals C. elegans Models to Study the Propagation of Prions and Prion-Like Proteins

Biomolecules ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 1188 ◽  
Author(s):  
Carl Alexander Sandhof ◽  
Simon Oliver Hoppe ◽  
Jessica Tittelmeier ◽  
Carmen Nussbaum-Krammer
Keyword(s):  
Neurodegenerative Diseases ◽  
Model Organism ◽  
Model Systems ◽  
Transmissible Spongiform Encephalopathies ◽  
Spongiform Encephalopathies ◽  
Population Demographics ◽  
C Elegans ◽  
Age Related ◽  
Bona Fide ◽  
High Degree

A hallmark common to many age-related neurodegenerative diseases, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS), is that patients develop proteinaceous deposits in their central nervous system (CNS). The progressive spreading of these inclusions from initially affected sites to interconnected brain areas is reminiscent of the behavior of bona fide prions in transmissible spongiform encephalopathies (TSEs), hence the term prion-like proteins has been coined. Despite intensive research, the exact mechanisms that facilitate the spreading of protein aggregation between cells, and the associated loss of neurons, remain poorly understood. As population demographics in many countries continue to shift to higher life expectancy, the incidence of neurodegenerative diseases is also rising. This represents a major challenge for healthcare systems and patients’ families, since patients require extensive support over several years and there is still no therapy to cure or stop these diseases. The model organism Caenorhabditis elegans offers unique opportunities to accelerate research and drug development due to its genetic amenability, its transparency, and the high degree of conservation of molecular pathways. Here, we will review how recent studies that utilize this soil dwelling nematode have proceeded to investigate the propagation and intercellular transmission of prions and prion-like proteins and discuss their relevance by comparing their findings to observations in other model systems and patients.

scholarly journals Chronic Exposure to Youthful Circulation Leads to Epigenetic Reprogramming and Lifespan Extension

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 682-682
Author(s):  
Bohan Zhang ◽  
David Lee ◽  
Alexander Tyshkovskiy ◽  
Akshay Bareja ◽  
Csaba Kerepesi ◽  
...  
Keyword(s):  
Chronic Exposure ◽  
Aging Process ◽  
Biological Age ◽  
Biological Aging ◽  
Lifespan Extension ◽  
Molecular Signatures ◽  
Signature Analysis ◽  
Rna Seq ◽  
Aging Research

Abstract Heterochronic parabiosis is a powerful rejuvenation model in aging research. Due to limitations in the duration of blood sharing and/or physical attachment, it is currently unclear if parabiosis retards the molecular signatures of aging or affects healthspan/lifespan in the mouse. Here, we describe a long-term heterochronic parabiosis model, which appears to slow down the aging process. We observed a “deceleration” of biological age based on molecular aging biomarkers estimated with DNA methylation clock and RNA-seq signature analysis. The slowing of biological aging was accompanied by systemic amelioration of aging phenotypes. Consistent with these findings, we found that aged mice, which underwent heterochronic parabiosis, had an increased healthspan and lifespan. Overall, our study re-introduces a prolonged parabiosis and detachment model as a novel rejuvenation therapy, suggesting that a systemic reset of biological age in old organisms can be achieved through the exposure to young environment.

scholarly journals An integrated analysis tool reveals intrinsic biases in gene set enrichment

2021 ◽  
Author(s):  
Nishant Thakur ◽  
Nathalie Pujol ◽  
Jacques van Helden ◽  
Robert H Waterston ◽  
LaDeana W Hillier ◽  
...  
Keyword(s):  
Large Scale ◽  
Model Organism ◽  
Integrated Analysis ◽  
Analysis Tool ◽  
Gene Set Enrichment ◽  
Phylogenetic Conservation ◽  
C Elegans ◽  
Gene Enrichment ◽  
Depth Study ◽  
The Universe

Generating meaningful interpretations of gene lists remains a challenge for all large-scale studies. Many approaches exist, often based on evaluating gene enrichment among pre-determined gene classes. Here, we conceived and implemented yet another analysis tool (YAAT), specifically for data from the widely-used model organism C. elegans. YAAT extends standard enrichment analyses, using a combination of co-expression data and profiles of phylogenetic conservation, to identify groups of functionally-related genes. It additionally allows class clustering, providing inference of functional links between groups of genes. We give examples of the utility of YAAT for uncovering unsuspected links between genes and show how the approach can be used to prioritise genes for in-depth study. Our analyses revealed several limitations to the meaningful interpretation of gene lists, specifically related to data sources and the "universe" of gene lists used. We hope that YAAT will represent a model for integrated analysis that could be useful for large-scale exploration of biological function in other species.

scholarly journals High-throughput imaging of Caenorhabditis elegans aging using collective activity monitoring

2021 ◽  
Author(s):  
Anthony D Fouad ◽  
Matthew A Churgin ◽  
Julia Hayden ◽  
Joyce Xu ◽  
Jeong-Inn Park ◽  
...  
Keyword(s):  
Large Scale ◽  
Imaging System ◽  
Activity Monitoring ◽  
Automated System ◽  
Aging Research ◽  
C Elegans ◽  
Collective Activity ◽  
Large Numbers ◽  
Natural Isolates ◽  
Rate Of Decline

The genetic manipulability and short lifespan of C. elegans make it an important model for aging research. Widely applied methods for measurements of worm aging based on manual observation are labor intensive and low-throughput. Here, we describe the Worm Collective Activity Monitoring Platform (WormCamp), a system for assaying aging in C. elegans by monitoring activity of populations of worms in standard 24-well plates. We show that metrics based on the rate of decline in collective activity can be used to estimate the average lifespan and locomotor healthspan in the population. Using the WormCamp, we assay a panel of highly divergent natural isolates of C. elegans and show that both lifespan and locomotor healthspan display substantial heritability. To facilitate analysis of large numbers of worms, we developed a robotic imaging system capable of simultaneous automated monitoring of activity, lifespan, and locomotor healthspan in up to 2,304 populations containing a total of ~90,000 animals. We applied the automated system to conduct a large-scale RNA interference screen for genes that affect lifespan and locomotor healthspan. The WormCamp system is complementary to other current automated methods for assessing C. elegans aging and is well suited for efficiently screening large numbers of conditions.

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