Establishment and application of a zebrafish model of Werner syndrome identifies sapanisertib as a potential antiaging drug.

ABSTRACT: Aging is a complex process that affects multiple organs, and the discovery of a pharmacological approach to ameliorate aging is considered the Holy Grail of medicine. Here, we performed an N-ethyl-N-nitrosourea forward genetic screening in zebrafish and identified an accelerated aging mutant named meteor (met), harboring a mutation in the Werner syndrome RecQ-like helicase (wrn) gene. Loss of wrn leads to a short lifespan and age-related characteristics in the intestine of zebrafish embryos, such as cellular senescence, genomic instability, and epigenetic alteration. Therefore, we conducted a screening of antiaging drugs using the met mutant and revealed that sapanisertib effectively ameliorated most of the aging phenotypes of the mutant. Me

SUBMITTER: Ma J 

PROVIDER: S-EPMC11804616 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature