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105/01/2023
A Platform for Rapid Exploration of Aging and Diseases in a Naturally Short-Lived Vertebrate
Pizzaclub, 20th April 2016
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The African turquoise killifish
Killifish comes from Africa (Zimbabwe and Mozambique)
Very short duration of the rain season the natural lifespan is limited to a few months
Even in the lab very short lifespan
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Model organisms to study agingo C. elegans, yeast and
drosophila• Short lifespan but not
vertebrateo Mice and zebrafish
• Vertebrate but not short lifespan
o Other advantages:• Conserved aging genes• XY-based sexual determination
o Killifish• Vertebrate and short lifespan
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Telomeres and telomerase (TERT)
o Killifish has similar telomeres length like human (6-8 kb) unlike mice (50-150kb)
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A platform for the study of Hallmarks of aging genes in vertebrates
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Modeling Telomere Attrition
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Modeling Telomere Attrition – model validationo First generation looks normal
o Complete loss of telomerase activity
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Modeling Telomere Attritiono Age dependent fertilityo Age-dependent defect of the germlineo Defects in other highly proliferative
tissues (blood, intestine)o No significant defects in low-proliferative
tissues
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Genetic anticipationo Age dependento Generation dependent
o Genetic anticipation: is a phenomenon in which symptoms of a genetic disorder are increased in severity or become apparent at an earlier age in the next generation
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Genome precise editing – point mutation
Dyskeratosis congenital: a disease caused by a mutation in K902 in human TERT
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Genome precise editing – short sequence knock-in
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A Toolbox of Turquoise Killifish Mutants Encompassing the Hallmark of Aging
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Thank you.