Is Gcn4-induced autophagy the ultimate downstream mechanism by which hormesis extends yeast replicative lifespan?

The number of times a cell divides before irreversibly arresting is termed replicative lifespan. Despite discovery of many chemical, dietary and genetic interventions that extend replicative lifespan, usually first discovered in budding yeast and subsequently shown to apply to metazoans, there is st...

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Bibliographic Details
Published in:Current genetics 2019-06, Vol.65 (3), p.717-720
Main Authors: Shen, Zih-Jie, Postnikoff, Spike, Tyler, Jessica K.
Format: Article
Language:English
Subjects:
Autophagy
Biochemistry
Biomedical and Life Sciences
Cell Biology
Chemical synthesis
Hormesis
Life Sciences
Life span
Microbial Genetics and Genomics
Microbiology
Mini-Review
Molecular modelling
Organic chemistry
Phagocytosis
Plant Sciences
Protein biosynthesis
Protein synthesis
Proteins
Proteomics
Reduction
Transcription
Yeast
Yeasts
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Summary:The number of times a cell divides before irreversibly arresting is termed replicative lifespan. Despite discovery of many chemical, dietary and genetic interventions that extend replicative lifespan, usually first discovered in budding yeast and subsequently shown to apply to metazoans, there is still little understanding of the underlying molecular mechanisms involved. One unifying theme is that most, if not all, interventions that extend replicative lifespan induce “hormesis”, where a little inflicted damage makes cells more able to resist similar challenges in the future. One of the many cellular changes that occur during hormesis is a global reduction in protein synthesis, which has been linked to enhanced longevity in many organisms. Our recent study in budding yeast found that it was not the reduction in protein synthesis per se, but rather the subsequent induction of the conserved Gcn4 transcriptional regulator and its ability to induce autophagy that was responsible for extending replicative lifespan. We propose that Gcn4-dependent induction of autophagy occurring downstream of reduced global protein synthesis may be a unifying molecular mechanism for many interventions that extend replicative lifespan.
ISSN:0172-8083
1432-0983
DOI:10.1007/s00294-019-00936-4