Annual Fish as a Tool for Screening for Antiaging Drugs

In 1999, we suggested that zebrafish could be used as a model for drug discovery (Jagadeeswaran et al., 1999). Due to the availability of a large number of chemical compounds and the ease of screening the larvae, a number of mutants are being investigated to reverse the phenotype with these chemicals. Such reversal of phenotypes has been applied to aortic coarctation (Peterson et al., 2004). This phenotypic reversal is feasible because the larvae are small and it is possible to accommodate screening in a 96-well format in tiny volumes such that only small amounts of chemical are used. However, in longevity studies such screening depends on the availability of compounds on a large scale and continuous replacement of the chemicals to accommodate for their half-lives. Interestingly, there are several naturally occurring compounds that are either antioxidants or participate in metabolic pathways that affect aging. Thus, in the future, it is anticipated that large-scale screens could be undertaken using Nothobranchius as a model to discover more new natural products that may have an effect on the extension of lifespans. For example, individual leaf extracts could be placed in tanks of Nothobranchius fish to see which of these extracts would prolong the lifespan. Once the extract is identified, the active compounds could be characterized and be synthesized by pharmaceutical companies. Thus, Nothobranchius could be useful in rapidly discovering drugs that will extend vertebrate lifespan.

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