The microscopic Caenorhabditis elegans has been extensively used in aging research for the past several decades due to its numerous unique characteristics. Extensive work in the field is devoted to identifying pro-longevity compounds and further contributing to human healthspan. We have established an automated system for the identification of potential pro-longevity compounds acting during development via inducing mild mitochondrial stress. This is a new C. elegans screening strategy that can drastically accelerate the discovery of potential life extending compounds.
At present, drug screening is mainly carried out in single cells systems, targeting enhancers or suppressors of selected readout(s). However, it is limited when testing for compounds with effects at the organismal level. In the past decade, different model organisms have been employed to carry out modifier screenings. Thanks to the short lifespan, simple anatomy, stereotyped phenotypes and behaviors, and genetic tractability, C. elegans is an optimal model organism for screening potential drugs that influence aging and age-associated phenotypes. In addition, the lifespan of nematode can be determined robustly and reproducibly. Previous studies have demonstrated the worms as an efficient pharmacological tool to identify a number of small molecules with a pro-longevity effect. With the development of automated systems for preparation and imaging, the throughput of drug screening has been greatly increased. However, the process of scoring animals' survival for the entire lifespan is still time-consuming, which remains a bottleneck for the fast discovery of pro-longevity compounds. Notably, almost all of 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. This is a better option allowing less experimental time spending thanks to the high homology genes between nematodes and mammals.
Mitochondria is a highly dynamic organelle that plays an important role in cellular homeostasis and organismal health. Since mitochondrial deterioration is a central feature of normal aging, manifesting concurrent alterations in their morphology with time. Here we exploit the differential C. elegans phenotypic and biochemical changes associated with mild mitochondrial stress, as surrogate markers to establish a phenotypic-based screening to identify pro-longevity compounds targeting mitochondria. The C. elegans mitochondrial mutants are generated from treating with a mild or a strong dose of RNAi against different nuclear-encoded mitochondrial proteins.
We have developed an automated system based on the Cellomics ArrayScan® VTI HCS Reader (Thermo Scientific) imaging platform and the Spot Detector (one of its BioApplications). The high-content screenings (HCS) instrument has different BioApplications, and can measure animals' size (including area and length) as well as counting and detection of animals with specific phenotypes. The Spot Detector can quantify the distribution and intensity of fluorescently tagged proteins in transgenic animals.
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.
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