CRISPR,衰老研究模型 z-bo 2020-12-21 286

　　Since existing vertebrate models (such as mice) have relatively long lifespans, and short-lived invertebrates (such as yeast and nematodes) lack some of the key characteristics of humans, studying aging and related diseases has always been a challenge.

　　 Now scientists at Stanford University have found a solution for both. They used a genome editing toolbox to build a platform that can study aging in the natural short-lived African turquoise killifish. Researchers hope that these fish will become a valuable new model for understanding, preventing and treating senile diseases. They published this research work in the February 12 issue of Cell.

　　African medaka live in temporary ponds that disappeared during the dry season in Zimbabwe and Mozambique. Therefore, unlike their counterparts living in persistent waters, they have evolved into a short life span of only 4-6 months, which makes them excellent candidates for aging research. However, until now, there are few genetic tools available to study them.

　　Using the recently developed CRISPR/Cas-based genome editing technology, researchers have constructed the platform required to use this medaka in experiments (extended reading: Nature sub-publishes new light-induced CRISPR technology). Dr. Anne Brunet, a senior author of the paper and professor of genetics at Stanford University School of Medicine, said: "This means that you can understand all its genes and manipulate or mutate them in various ways to better understand aging and senile diseases."

　　 Some medaka mutants have shown promising applications in aging and disease research. Itamar Harel, the lead author of the paper and a postdoctoral researcher in genetics, said: “One of our medaka mutants reproduced a human disease caused by telomere defects in a rapid way: congenital dyskeratosis. (Dyskeratosis congenita). These medaka mutants have blood and intestinal defects like humans, and show some fertility problems."

　　 Now that the research team has generated tools to quickly manipulate medaka, this model organism can be used to screen for genes and drugs that delay or reverse aging and age-related diseases.

　　 Dr. Brunet said: “Understanding the mechanism by which genomes encode complex features such as lifespan is one of the biggest challenges of modern biology. The model system, tools and resources we have constructed can help meet this challenge.”