Killifish in Aging Research
Most aging research starts in short-lived species far removed from our own in the tree of life. There is a trade-off involved: it is much cheaper to explore and experiment with interventions in aging in a short-lived species, but the more distant the species the less likely that the results will be useful for longer-lived mammals. Fortunately many of the fundamental mechanisms relevant to aging are very similar across most of the animal kingdom, and even between yeast and humans. Low-cost exploration is very necessary in a field with little funding and an enormous, complex problem space. Without the use of flies, worms, and other short-lived species, most aging research would simply never happen. In recent years killifish have been inducted into the list of species used for aging research, which is an involved process in and of itself. This article looks at some of the high points:
Of the many varieties of killifish, the turquoise killifish (Nothobranchius furzeri) has the shortest lifespan - the briefest of any vertebrate bred in captivity, ranging from 3 to 12 months depending on strain and living conditions. Using killifish to study ageing is not a new idea. In the late twentieth century, scientists studied ageing in one species, Nothobranchius guentheri, that lives for about 14 months. But given techniques available at the time, they could come up with only basic descriptions of ageing features. Now, however, advances in molecular analysis have set up excellent conditions in which to develop the model and investigate mechanisms behind its dotage. The killifish's brief lifespan, relative to those of longer-lived models such as mice and zebrafish, enables ageing research to progress apace. And because the fish is a vertebrate, the research is more directly relevant to people than are studies of short-lived organisms such as fruit flies or nematodes.
The ephemeral existence that so appeals to scientists is an evolutionary adaptation to the fish's natural environment: their accelerated development enables them to live and reproduce in transient mud pools during the wet season in equatorial Africa. But that begged another question: would killifish age in a way that parallels the human process? The answer is yes: the fish do get 'old' before they die. Having shown that killifish decline with age, scientists now want to understand how the process occurs. One key resource is the collection of several strains from Africa whose genomes are not identical. By cross-breeding two strains, researchers created fish with a range of lifespans. They then compared the genomes and longevities of parent and second-generation progeny, and identified a few chromosomal regions, each with hundreds of genes that might influence ageing. Although these did not directly reveal genes involved in longevity, they suggested possible candidates. From this study, the scientists estimated that about 32% of variation in lifespan among turquoise killifish results from genetics, a figure comparable to the 20-35% estimated genetic contribution in mice.
It would be cool if someone could create a chart showing the cost, time, and experience levels necessary to carry out an experiment (e.g. gene therapy) in each of the model organisms from worm to fly to fish to mouse.