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

MPG-Autoren

Harel,  I.
Max Planck Institute for Biology of Ageing, Max Planck Society;

Benayoun,  B. A.
Max Planck Institute for Biology of Ageing, Max Planck Society;

Machado,  B.
Max Planck Institute for Biology of Ageing, Max Planck Society;

Singh,  P. P.
Max Planck Institute for Biology of Ageing, Max Planck Society;

Hu,  C. K.
Max Planck Institute for Biology of Ageing, Max Planck Society;

Pech,  M. F.
Max Planck Institute for Biology of Ageing, Max Planck Society;

Valenzano,  D. R.
Max Planck Institute for Biology of Ageing, Max Planck Society;

Zhang,  E.
Max Planck Institute for Biology of Ageing, Max Planck Society;

Sharp,  S. C.
Max Planck Institute for Biology of Ageing, Max Planck Society;

Artandi,  S. E.
Max Planck Institute for Biology of Ageing, Max Planck Society;

Brunet,  A.
Max Planck Institute for Biology of Ageing, Max Planck Society;

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Zitation

Harel, I., Benayoun, B. A., Machado, B., Singh, P. P., Hu, C. K., Pech, M. F., et al. (2015). A platform for rapid exploration of aging and diseases in a naturally short-lived vertebrate. Cell, 160(5), 1013-26. doi:10.1016/j.cell.2015.01.038.


Zitierlink: http://hdl.handle.net/11858/00-001M-0000-0028-58FE-2
Zusammenfassung
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.