Sis2 regulates yeast replicative lifespan in a dose-dependent manner

被引:3
作者
Ölmez T.T. [1 ,2 ,3 ,6 ]
Moreno D.F. [1 ,2 ,7 ]
Liu P. [1 ,2 ]
Johnson Z.M. [4 ]
McGinnis M.M. [5 ]
Tu B.P. [5 ]
Hochstrasser M. [1 ,4 ]
Acar M. [1 ,2 ,6 ]
机构
[1] Department of Molecular Cellular and Developmental Biology, Yale University, 219 Prospect Street, New Haven, 06511, CT
[2] Systems Biology Institute, Yale University, 850 West Campus Drive, West Haven, 06516, CT
[3] Koç University Research Center for Translational Medicine, Koç University, Rumelifeneri Yolu, Sarıyer, İstanbul
[4] Department of Molecular Biophysics and Biochemistry, Yale University, 266 Whitney Avenue, New Haven, 06520, CT
[5] Department of Biochemistry, UT Southwestern Medical Center, Dallas, 75390, TX
[6] Department of Basic Medical Sciences, Koc University Rumelifeneri Yolu, Sarıyer, İstanbul
[7] Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch-Graffenstaden
基金
美国国家卫生研究院;
关键词
D O I
10.1038/s41467-023-43233-y
中图分类号
学科分类号
摘要
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. © 2023, The Author(s).
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