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Sis2 regulates yeast replicative lifespan in a dose-dependent manner

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  • Tolga T. Ölmez

    (Yale University
    Yale University
    Koç University, Rumelifeneri Yolu, Sarıyer
    Koc University Rumelifeneri Yolu, Sarıyer)

  • David F. Moreno

    (Yale University
    Yale University
    Institut de Génétique et de Biologie Moléculaire et Cellulaire)

  • Ping Liu

    (Yale University
    Yale University)

  • Zane M. Johnson

    (Yale University)

  • Madeline M. McGinnis

    (UT Southwestern Medical Center)

  • Benjamin P. Tu

    (UT Southwestern Medical Center)

  • Mark Hochstrasser

    (Yale University
    Yale University)

  • Murat Acar

    (Yale University
    Yale University
    Koc University Rumelifeneri Yolu, Sarıyer)

Abstract

Application of microfluidic platforms facilitated high-precision measurements of yeast replicative lifespan (RLS); however, comparative quantification of lifespan across strain libraries has been missing. Here we microfluidically measure the RLS of 307 yeast strains, each deleted for a single gene. Despite previous reports of extended lifespan in these strains, we found that 56% of them did not actually live longer than the wild-type; while the remaining 44% showed extended lifespans, the degree of extension was often different from what was previously reported. Deletion of SIS2 gene led to the largest RLS increase observed. Sis2 regulated yeast lifespan in a dose-dependent manner, implying a role for the coenzyme A biosynthesis pathway in lifespan regulation. Introduction of the human PPCDC gene in the sis2Δ background neutralized the lifespan extension. RNA-seq experiments revealed transcriptional increases in cell-cycle machinery components in sis2Δ background. High-precision lifespan measurement will be essential to elucidate the gene network governing lifespan.

Suggested Citation

  • Tolga T. Ölmez & David F. Moreno & Ping Liu & Zane M. Johnson & Madeline M. McGinnis & Benjamin P. Tu & Mark Hochstrasser & Murat Acar, 2023. "Sis2 regulates yeast replicative lifespan in a dose-dependent manner," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43233-y
    DOI: 10.1038/s41467-023-43233-y
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    Cited by:

    1. 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 & Zhengw, 2024. "The de novo design and synthesis of yeast chromosome XIII facilitates investigations on aging," Nature Communications, Nature, vol. 15(1), pages 1-12, December.

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