20042016_pizzaclub_part1

A new fish model for aging research.

1. 4/20/2016 A Platform for Rapid Exploration of Aging and Diseases in a Naturally Short-Lived Vertebrate Pizzaclub , 20 th April 2016 [email protected]

2. The African turquoise k illifish 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

3. Model organisms to study aging C. elegans, yeast and drosophila Short lifespan but not vertebrate Mice and zebrafish Vertebrate but not short lifespan Other advantages: Conserved aging genes XY-based sexual determination Killifish Vertebrate and short lifespan

4. Telomeres and telomerase (TERT) Killifish has similar telomeres length like human (6-8 kb) unlike mice (50-150kb)

5. A platform for the study of Hallmarks of aging genes in vertebrates

6. Modeling Telomere Attrition

7. Modeling Telomere Attrition – model validation First generation looks normal Complete loss of telomerase activity

8. Modeling Telomere Attrition Age dependent fertility Age-dependent defect of the germline Defects in other highly proliferative tissues (blood, intestine) No significant defects in low-proliferative tissues

9. Genetic anticipation Age dependent Generation dependent 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

10. Genome precise editing – point mutation Dyskeratosis congenital: a disease caused by a mutation in K902 in human TERT

11. Genome precise editing – short sequence knock-in

12. A Toolbox of Turquoise Killifish Mutants Encompassing the Hallmark of Aging

13. Thank you.