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Oliver Pusch

Nothobranchius furzeri as an Emerging Model for Aging in Vertebrates

Research Focus
Aging is arguably the most familiar yet least well-understood aspect of human biology. Much of what we know about the molecular biology of the aging process today derives from invertebrate model species like yeast, worm and fly. A major drawback of vertebrate model systems, such as mouse or zebrafish is their relatively long lifespan of up to five years, which makes the validation of results obtained in invertebrates time-consuming and expensive.

Main Objectives
Recently, the short-lived African turquoise killifish Nothobranchius furzeri has been recognized for its potential to become a central model system in the field of aging research. N. furzeri is a naturally short lived vertebrate that inhabits temporary ponds in South-East Africa. In laboratory conditions, the turquoise killifish exhibits a maximal lifespan of 4-6 months, making it the shortest-lived vertebrate species bred in the lab. In 2015, successful targeted genome editing using the CRISPR/Cas9 technology to create transgenic fish lines was reported. Combined with information of the newly assembled reference genome, the African turquoise killifish, opens the door to in vivo modeling of vertebrate aging and aging-related diseases.

Content of Research (The Austrian Notho Project)
We established a fully operating Nothobranchius fish facility housing both a short-lived, highly inbred strain (GRZ) and a long-lived strain (MZM-04/10). Using the African turquoise killifish as a model system we aim to understand how aging is affected by both genetic and non-genetic factors. A role for epigenetics in ageing is supported by evidence that chromatin is altered during the ageing pro¬cess, resulting in aberrant gene expression and disturbances in broad genome architecture and the epigenomic landscape. In particular, we are interested in the role of chromatin modifiers in modulating lifespan. The potential reversibility of epigenetic changes offers exciting opportunities to develop chromatin-based strategies to counter or even reverse aging or age-related diseases.