Abstract

Ageing-related proteins play various roles such as regulating cellular ageing, countering oxidative stress, and modulating signal transduction pathways amongst many others. Hundreds of ageing-related proteins have been identified, however the functions of most of these ageing-related proteins are not known. Here, we report the identification of proteins that extended yeast chronological life span (CLS) from a screen of ageing-related proteins. Three of the CLS-extending proteins, Ptc4, Zwf1, and Sme1, contributed to an overall higher survival percentage and shorter doubling time of yeast growth compared to the control. The CLS-extending proteins contributed to thermal and oxidative stress responses differently, suggesting different mechanisms of actions. The overexpression of Ptc4 or Zwf1 also promoted rapid cell proliferation during yeast growth, suggesting their involvement in cell division or growth pathways.

Highlights

  • Ageing-related proteins play various roles such as regulating cellular ageing, countering oxidative stress, and modulating signal transduction pathways amongst many others

  • To determine the effects of the overexpressed proteins on yeast chronological life span (CLS), we overexpressed ageing-related proteins in yeast and screened them using outgrowth kinetics assay in a high-throughput manner (Fig. 1a)[1]

  • For the gene deletion mutants, an aliquot of culture was sampled for outgrowth in a 96-well microplate containing fresh Yeast Peptone Dextrose (YPD) media

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Summary

Introduction

Ageing-related proteins play various roles such as regulating cellular ageing, countering oxidative stress, and modulating signal transduction pathways amongst many others. We report the identification of proteins that extended yeast chronological life span (CLS) from a screen of ageing-related proteins. A CLS screen of deletion mutants revealed genes that significantly extended CLS (ACB1, CKA2, TRM9) and the deletion of these genes promoted heat-shock ­tolerance[7] Another screen of deletion mutants found that while autophagy defective mutants (ATGmutants) decreased CLS, highly conserved de novo purine biosynthesis pathway defective mutants (the ADE mutants) extended CLS to the same degree as calorie r­ estriction[8]. In another CLS screen, CYR​1 and SCH9 mutants were found to extend CLS and increase thermal and oxidative stress t­olerances[9].

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