The continuous discovery of new chemicals and small molecules over the past decades has led to the development of automated platforms that facilitate the rapid screening of many compounds and the rapid assessment of de-biological or biochemical activities. As a model organism, C. elegans is an optimal model organism for screening potential drugs affecting aging and age-related phenotypes due to its short lifespan, anatomical simplicity, phenotypic and behavioral fixation, and genetic ease of handling. CD BioSciences specializes in C. elegans research and provides customized pro-longevity compound screening service to our clients globally. We utilize state-of-the-art technology and expertise to help you identify and characterize compounds with the potential to promote longevity and improve overall health longevity.
At present, drug screening is mainly carried out in single cells systems, targeting enhancers or suppressors of selected readout(s). However single cell systems are limited when testing compounds with effects at the biological level. To overcome this drawback, the use of different model organisms for modifier screening has grown rapidly over the last few decades. Mice are widely used in medical research because they are physiologically similar to humans, but have the disadvantages of being long-lived, expensive and time-consuming. To overcome these drawbacks, researchers have started using different invertebrates as model organisms for drug screening.
Previous studies have shown that worms are an effective pharmacological tool to recognize many small molecules with long-lived effects.
This is a better option allowing less experimental time spending thanks to the high homology genes between nematodes and mammals.
Notably, almost all the known C. elegans long-lived mutants present the prolonged longevity accompanied with alteration phenotypes (associated with longevity genes), making it possible to establish surrogate phenotypes (markers) for life extension.
Due to the advantages of short lifespan, fixed phenotype and behavior, and ease of genetic manipulation, C. elegans is the best model organism for studying drugs that affect aging and age-related phenotypes.
With the development of automated systems for preparation and imaging, the throughput of drug screening has greatly increased. As a leading provider of customized services for C. elegans research, CD BioSciences has proven and advanced automation platforms, and our dedicated team of professionals is committed to providing you with reliable, efficient, and cost-effective solutions to help you screen long-lived compounds.
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Culturing C. elegans: C. elegans is cultured on agar plates inoculated with E. coli (OP 50). |
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Compound Library Preparation: Prepare a compound library consisting of natural compounds, synthetic chemicals, or drug candidates according to the research objectives. |
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Compound Exposure: Cultured C. elegans are exposed to the target compounds by direct exposure, liquid exposure and feeding exposure. |
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Phenotype Analysis: When C. elegans are exposed to compounds, their lifespan and overall health are examined, including survival curves as well as mobility, reproduction, and other age-related phenotypes. |
CD BioSciences is a dedicated provider of C. elegans model services. C. elegans is extensively used in drug screening, including pro-longevity compounds. To accelerate the discovery of potential life-extending compounds, we have developed a new strategy using C. elegans mitochondrial mutants and the automated microscopy platform. If you are interested in our service, please feel free to contact us for more information.
Background
The C. elegans model provides several advantages when performing chemical screening for the identification of drug candidates. This is especially true for primary drug screening, which involves relatively smaller spaces, lower costs, and time-consuming assessments. Nematodes can be inexpensively cultured in large quantities, and the relatively short lifespan of C. elegans ensures this organism provides high-throughput screening for anti-aging drug. Also, the effects of drugs can be tested directly in the whole organism, such that compounds that are toxic for development can be eliminated immediately. C. elegans epigenetic research can also be used for genetic analysis and investigations of chemical interventions for longevity. Besides acting as markers for the genetic regulation during aging, epigenetic mechanisms may also be targets for drug screening in aging or age-related diseases.
Pro-longevity Compound High-throughput Screening
A variety of assays suitable for high-throughput screening for anti-aging compounds are currently being developed. Based on mutations in the age-1(PI3K) or daf-2(INSR) genes, and reduction in the daf-16(foxo) mutant.
Pro-longevity Compound Screening Examples
Many potential chemical candidates for extending lifespan are currently being investigated, including the following aging modulating compounds:
• Metformin (biguanide anti-glycemic agent for AMPK activation)
• Rapamycin (immunosuppressing agent and mTOR inhibitor)
• Resveratrol (polyphenol and sirtuin activator)
• Spermidine (polyamine and inductor of autophagy)
• Aspirin (COX inhibitor, antithrombosis, and antioxidant)
• Masoprocol (catechol with antioxidant and anti-inflammatory properties)
In Vitro Toxicity Testing
The toxicity ranking screening of C. elegans has been repeatedly found to be as predictive of rat LD50 ranking as mouse LD50 ranking. Additionally, many instances of the conservation of the mode of toxic action have been reported between mammals. These consistent correlations make a case for the inclusion of C. elegans assays in early safety testing and as one component in tiered or integrated toxicity testing strategies. These findings indicate that C. elegans could be a bridge between in vitro assays and mammalian toxicity testing by combining established in vitro handling techniques and cost ratios with oral toxicity test data from an intact organism. Given that nematodes lack most mammalian organs, it is unrealistic to expect that any combination of C. elegans assays alone will replace in-depth descriptive toxicology analyses in mammals. However, although organismal toxicity endpoints often differ, many pathways of toxicity and modes of toxic action are conserved between worms and humans.
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