• Open Access

Molecular phenotyping of aging in single yeast cells using a novel microfluidic device

Authors

  • Zhengwei Xie,

    1. Center for Quantitative Biology, and the State Key Laboratory for Artificial Microstructures and Mesoscopic Physics, School of Physics, Peking University, Beijing 100871, China
    2. Department of Biochemistry and Biophysics and California Institute for Quantitative Biosciences, University of California, San Francisco, CA 94143, USA
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  • Yi Zhang,

    1. Center for Quantitative Biology, and the State Key Laboratory for Artificial Microstructures and Mesoscopic Physics, School of Physics, Peking University, Beijing 100871, China
    2. Department of Biochemistry and Biophysics and California Institute for Quantitative Biosciences, University of California, San Francisco, CA 94143, USA
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  • Ke Zou,

    1. Center for Quantitative Biology, and the State Key Laboratory for Artificial Microstructures and Mesoscopic Physics, School of Physics, Peking University, Beijing 100871, China
    2. Department of Biochemistry and Biophysics and California Institute for Quantitative Biosciences, University of California, San Francisco, CA 94143, USA
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  • Onn Brandman,

    1. Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94143, USA
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  • Chunxiong Luo,

    1. Center for Quantitative Biology, and the State Key Laboratory for Artificial Microstructures and Mesoscopic Physics, School of Physics, Peking University, Beijing 100871, China
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  • Qi Ouyang,

    1. Center for Quantitative Biology, and the State Key Laboratory for Artificial Microstructures and Mesoscopic Physics, School of Physics, Peking University, Beijing 100871, China
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  • Hao Li

    1. Department of Biochemistry and Biophysics and California Institute for Quantitative Biosciences, University of California, San Francisco, CA 94143, USA
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Hao Li, Department of Biochemistry and Biophysics and California Institute for Quantitative Biosciences, University of California, San Francisco, CA 94143, USA. Tel.: 01415 502 8187; fax: 01415 514 2617; e-mail: haoli@genome.ucsf.edu and Qi Ouyang, Center for Quantitative Biology, and the State Key Laboratory for Artificial Microstructures and Mesoscopic Physics, School of Physics, Peking University, Beijing 100871, China. Tel.: 861062756943; fax: 861062759595; e-mail qi@pku.edu.cn

Summary

Budding yeast has served as an important model organism for aging research, and previous genetic studies have led to the discovery of conserved genes/pathways that regulate lifespan across species. However, the molecular causes of aging and death remain elusive, because it is very difficult to directly observe the cellular and molecular events accompanying aging in single yeast cells by the traditional approach based on micromanipulation. We have developed a microfluidic system to track individual mother cells throughout their lifespan, allowing automated lifespan measurement and direct observation of cell cycle dynamics, cell/organelle morphologies, and various molecular markers. We found that aging of the wild-type cells is characterized by an increased general stress and a progressive lengthening of the cell cycle for the last few cell divisions; these features are much less apparent in the long-lived FOB1 deletion mutant. Following the fate of individual cells revealed that there are different forms of cell death that are characterized by different terminal cell morphologies, and associated with different levels of stress and lifespan. We have identified a molecular marker – the level of the expression of Hsp104, as a good predictor for the lifespan of individual cells. Our approach allows detailed molecular phenotyping of single cells in the process of aging and thus provides new insight into its mechanism.

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