Telomere Science Library

Publications, Presentations, and Videos
about the Nobel-Prize Winning Science of Telomere Biology

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

Authors: Itamar I. Harel, Bérénice A BA. Benayoun, Ben B. Machado, Param Priya PP. Singh, Chi-Kuo CK. Hu, Matthew F MF. Pech, Dario Riccardo DR. Valenzano, Elisa E. Zhang, Sabrina C SC. Sharp, Steven E SE. Artandi, Anne A. Brunet
Published: 02/12/2015, Cell

Video Abstract

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.

Copyright © 2015 Elsevier Inc. All rights reserved.
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