Screening and characterization of aging regulators using synthesized yeast chromosome XIII

Abstract

Yeast, a single eukaryotic cell model organism, demonstrates a progressive aging process. In the era of synthetic biology, study of the impact of synthetic chromosomes and aging is urgent and intriguing. Herein, we successfully constructed the 884 Kb synXIII of Saccharomyces cerevisiae and conducted replicative aging studies using the synthetic strains. We verified that the rRNA-related transcriptional factor RRN9 is a major positive controller of replicative lifespan. Using SCRaMbLE and an HSP104 reporter as a biomarker for mutant discovery, we screened 135 SCRaMbLEd synXIII strains with extended lifespan and identified 10 genes on synXIII that potentially serve as aging regulators. In addition, the genome-scale regression analysis of long-replicative lifespan SCRaMbLEd strains revealed distinct dysregulation of nucleus, ribosome, and mitochondrion function networks. Our findings suggest that Sc2.0 yeast has potential for unveiling new aging-related genes and gene-gene interactions underlying replicative lifespan.