The de novo design and synthesis of yeast chromosome XIII facilitates investigations on aging.

Chun Zhou, Yun Wang, Yikun Huang, Yongpan An, Xian Fu, Daqian Yang, Yilin Wang, Jintao Zhang, Leslie A Mitchell, Joel S Bader, Yizhi Cai, Junbiao Dai, Jef D Boeke, Zhiming Cai, Zhengwei Xie, Yue Shen, Weiren Huang

The First Affiliated Hospital of Shenzhen University; Shenzhen Second People's Hospital; Medical Innovation Technology Transformation Center of Shenzhen Second People's Hospital, Institute for Advanced Study, Synthetic Biology Research Center, International Cancer Center of Shenzhen University, Shenzhen, 518039, China.The First Affiliated Hospital of Shenzhen University; Shenzhen Second People's Hospital; Medical Innovation Technology Transformation Center of Shenzhen Second People's Hospital, Institute for Advanced Study, Synthetic Biology Research Center, International Cancer Center of Shenzhen University, Shenzhen, 518039, China. · pubmed

Paper

Abstract

In the era of synthetic biology, design, construction, and utilization of synthetic chromosomes with unique features provide a strategy to study complex cellular processes such as aging. Herein, we successfully construct the 884 Kb synXIII of Saccharomyces cerevisiae to investigate replicative aging using these synthetic strains. We verify that up-regulation of a rRNA-related transcriptional factor, RRN9, positively influence replicative lifespan. Using SCRaMbLE system that enables inducible whole-genome rearrangement on synXIII, we obtain 20 SCRaMbLEd synXIII strains with extended lifespan. Transcriptome analysis reveal the expression of genes involve in global protein synthesis is up-regulated in longer-lived strains. We establish causal links between genotypic change and the long-lived phenotype via reconstruction of some key structural variations observed in post-SCRaMbLE strains and further demonstrate combinatorial effects of multiple aging regulators on lifespan extension. Our findings underscore the potential of synthetic yeasts in unveiling the function of aging-related genes.

The following analysis is generated by AI and may contain errors. It is separate from the authors’ abstract and is not peer review.

Research summary

The paper is relevant to longevity research as it investigates the mechanisms of replicative aging in yeast through synthetic biology approaches. The construction of synthetic chromosomes and the exploration of genetic factors influencing lifespan extension contribute to understanding the biological processes underlying aging. While the findings are significant and provide insights into aging-related genes, the impact is moderate as it primarily focuses on a model organism and may not directly translate to higher organisms or humans.

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