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A new fish model for aging research.

Published in: Science
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  1. 1. 14/21/2016 A Platform for Rapid Exploration of Aging and Diseases in a Naturally Short-Lived Vertebrate Pizzaclub, 20th April 2016
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  3. 3. 3 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
  4. 4. 4 Model organisms to study aging o C. elegans, yeast and drosophila • Short lifespan but not vertebrate o Mice and zebrafish • Vertebrate but not short lifespan o Other advantages: • Conserved aging genes • XY-based sexual determination o Killifish • Vertebrate and short lifespan
  5. 5. 5 Telomeres and telomerase (TERT) o Killifish has similar telomeres length like human (6-8 kb) unlike mice (50-150kb)
  6. 6. 6 A platform for the study of Hallmarks of aging genes in vertebrates
  7. 7. 7 Modeling Telomere Attrition
  8. 8. 8 Modeling Telomere Attrition – model validation o First generation looks normal o Complete loss of telomerase activity
  9. 9. 9 Modeling Telomere Attrition o Age dependent fertility o Age-dependent defect of the germline o Defects in other highly proliferative tissues (blood, intestine) o No significant defects in low-proliferative tissues
  10. 10. 10 Genetic anticipation o Age dependent o 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
  11. 11. 11 Genome precise editing – point mutation Dyskeratosis congenital: a disease caused by a mutation in K902 in human TERT
  12. 12. 12 Genome precise editing – short sequence knock-in
  13. 13. 13 A Toolbox of Turquoise Killifish Mutants Encompassing the Hallmark of Aging
  14. 14. 14
  15. 15. 15 Thank you.