The short-lived African turquoise killifish: an emerging experimental model for ageing

Abstract

Human ageing is a fundamental biological process that leads to functional decay, increased risk for various diseases and, ultimately, death. Some of the basic biological mechanisms underlying human ageing are shared with other organisms; thus, animal models have been invaluable in providing key mechanistic and molecular insights into the common bases of biological ageing. In this Review, we briefly summarise the major applications of the most commonly used model organisms adopted in ageing research and highlight their relevance in understanding human ageing. We compare the strengths and limitations of different model organisms and discuss in detail an emerging ageing model, the short-lived African turquoise killifish. We review the recent progress made in using the turquoise killifish to study the biology of ageing and discuss potential future applications of this promising animal model.

Keywords: Age-associated diseases; Ageing; Longevity; Model organisms; Nothobranchius furzeri; Turquoise killifish.

Fig. 1.

Captive strains and the life cycle of the turquoise killifish. (A) Commonly used laboratory strains of the turquoise killifish: the short-lived strain (left; GRZ, yellow-tailed male fish) and long-lived strain (right; MZM-0403, red-tailed male fish). (B) Turquoise killifish life cycle (the time scale is based on the short-lived laboratory strain). Embryos can enter normal development or a developmentally arrested state called diapause, which lasts from a few weeks to several months and protects killifish during the dry season in the wild. Diapause consists of three different stages called diapause I, II and III. During the wet season in the wild (see main text) – and in laboratory conditions – hatched fry fully develop within 3-4 weeks and start spawning. Male fish are larger than females and have colourful fins and body, whereas the female fish are dull. Upon ageing (‘old’), fish lose body colour, fin structure deteriorates and the spine becomes bent. The age for young, young adult and old fish is indicated in weeks.

Fig. 2.

Side-by-side comparison of timing of transgenic line generation using genetic manipulations in the turquoise killifish, zebrafish and mouse. Synthesised single guide RNA (sgRNA) and Cas9 nucleases are injected into one-cell-stage embryos. Injected embryos are called F0 embryos. After hatching, transgenic fish are backcrossed to wild-type fish and generate F1 offspring. Further backcrosses are used to remove off-target mutations. Data are from the following references: turquoise killifish (Harel et al., 2015); zebrafish (Hwang et al., 2013; Jao et al., 2013); mouse (Wang et al., 2013).