A Review of the Use of C. Elegans in Aging Research

A great deal of early stage research into the mechanisms of aging takes place in very short-lived species such as the nematode worm Caenorhabditis elegans, and here researchers review the use of this species in the laboratory. Why research aging in species very different to our own? Because the economic advantages of being able to study a full life span of many individuals in a short time and at a low cost, coupled with a mature technology platform for genetic manipulation and analysis, more than offset the hurdles and dead ends that arise due to biological differences between nematodes and mammals. The fundamental mechanisms of metabolism and their relationship with aging are in fact surprisingly similar between very diverse species, a fortunate happenstance that speeds exploratory research.

Over a century ago, the zoologist Emile Maupas first identified the nematode, Rhabditis elegans, in the soil in Algiers. Subsequent work and phylogenic studies renamed the species Caenorhabditis elegans or more commonly referred to as C. elegans; (Caeno meaning recent; rhabditis meaning rod; elegans meaning nice). However, it was not until 1963, when Sydney Brenner, already successful from his work on DNA, RNA, and the genetic code, suggested the future of biological research lay in model organisms. Brenner believed that biological research required a model system that could grow in vast quantities in the lab, were cheap to maintain and had a simple body plan, and he chose the nematode C. elegans to fulfill such a role.

Why has C. elegans been used so successfully for aging research? What would make an organism suitable for aging research? The ability to easily and cheaply grow large quantities of worms in the lab is very helpful for aging research, especially when identifying long-lived mutants. C. elegans also have a relatively short lifespan (average approximately 17 days at 20 °C), and the lifespan is largely invariant. The latter allows for identification of mutants that shorten or lengthen average lifespan by as little as 10-15% and still be of statistical significance. Additional benefits of using C. elegans include that the entire genome is sequenced and annotated, the availability of an RNAi library comprising approx. 80% of the genes in the genome, the ease of generating transgenic strains and the recent development of gene-targeting approaches. This has allowed for extensive forward and reverse genetic screens for genes that modulate lifespan.

Another advantage working with C. elegans for studying the aging process is that the lifespan assay is straightforward, which allows for large numbers of worms to be assayed in a single experiment. Therefore, statistical significance can be tested in addition to the analysis of mortality rates. Together, these techniques allow one to comprehensively survey the worm genome for genes that modulate lifespan. This has led to the identification of more than 200 genes and regimens that modulate lifespan in C. elegans and revealed evolutionarily conserved pathways that modulate lifespan. Therefore, the combination of the short, invariant lifespan, ease of assays, ample genetic, molecular and genomic tools, and evolutionary conservation has allowed C. elegans to develop into a premiere model system for aging research.

Link: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4464094/


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