A platform for rapid exploration of aging and diseases in a naturally short-lived vertebrate

Cell. 2015 Feb 26;160(5):1013-1026. doi: 10.1016/j.cell.2015.01.038. Epub 2015 Feb 12.


Aging is a complex process that affects multiple organs. Modeling aging and age-related diseases in the lab is challenging because classical vertebrate models have relatively long lifespans. Here, we develop the first platform for rapid exploration of age-dependent traits and diseases in vertebrates, using the naturally short-lived African turquoise killifish. We provide an integrative genomic and genome-editing toolkit in this organism using our de-novo-assembled genome and the CRISPR/Cas9 technology. We mutate many genes encompassing the hallmarks of aging, and for a subset, we produce stable lines within 2-3 months. As a proof of principle, we show that fish deficient for the protein subunit of telomerase exhibit the fastest onset of telomere-related pathologies among vertebrates. We further demonstrate the feasibility of creating specific genetic variants. This genome-to-phenotype platform represents a unique resource for studying vertebrate aging and disease in a high-throughput manner and for investigating candidates arising from human genome-wide studies.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging
  • Animals
  • Base Sequence
  • CRISPR-Cas Systems
  • DNA-Directed DNA Polymerase / metabolism
  • Female
  • Genetic Techniques
  • Humans
  • Killifishes / genetics
  • Killifishes / physiology*
  • Male
  • Models, Animal
  • Molecular Sequence Data
  • Telomerase / genetics
  • Telomerase / metabolism
  • Vertebrates / physiology


  • Telomerase
  • DNA-Directed DNA Polymerase

Associated data

  • GENBANK/JNBZ00000000
  • SRA/SRP041421
  • SRA/SRP045718