105/01/2023

A Platform for Rapid Exploration of Aging and Diseases in a Naturally Short-Lived Vertebrate

Pizzaclub, 20th April 2016

remon.soliman@uni.lu

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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.