A new fish model for aging research.

1. 14/21/2016
A Platform for Rapid Exploration of Aging and
Diseases in a Naturally Short-Lived Vertebrate
Pizzaclub, 20th April 2016
remon.soliman@uni.lu

2. 2

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

6. 6
A platform for the study of Hallmarks of aging genes in vertebrates

7. 7
Modeling Telomere Attrition

8. 8
Modeling Telomere Attrition – model validation
o First generation looks normal
o Complete loss of telomerase activity

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

12. 12
Genome precise editing – short sequence knock-in

13. 13
A Toolbox of Turquoise Killifish Mutants Encompassing the Hallmark of Aging

14. 14

15. 15
Thank you.