Genes affecting the extension of chronological lifespan in <i>Schizosaccharomyces pombe</i> (fission yeast)

Ohtsuka, Hokuto; Shimasaki, Takafumi; Aiba, Hirofumi

doi:10.1111/mmi.14627

Cited by 22 publications

(26 citation statements)

References 175 publications

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“… 2014 , Ohtsuka et al . 2021b ). The restriction of Arg, which is an essential amino acid for chicken or salmon, but not for humans (Oda 2007 ), in Arg-auxotrophic cells also extends the chronological lifespan (Ohtsuka et al .…”

Section: Introductionmentioning

confidence: 99%

Response to leucine in Schizosaccharomyces pombe (fission yeast)

Ohtsuka

Shimasaki

Aiba

2022

FEMS Yeast Research

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Leucine (Leu) is a branched-chain, essential amino acid in animals, including humans. Fungi, including the fission yeast Schizosaccharomyces pombe, can biosynthesize Leu, but deletion of any of the genes in this biosynthesis leads to Leu auxotrophy. In this yeast, although a mutation in the Leu biosynthetic pathway, leu1-32, is clearly inconvenient for this species, it has increased its usefulness as a model organism in laboratories worldwide. Leu auxotrophy produces intracellular responses and phenotypes different from those of the prototrophic strains, depending on the growing environment, which necessitates a certain degree of caution in the analysis and interpretation of the experimental results. Under amino acid starvation, the amino acid-auxotrophic yeast induces cellular responses, which are conserved in higher organisms without the ability of synthesizing amino acids. This mini-review focuses on the roles of Leu in S. pombe and discusses biosynthetic pathways, contribution to experimental convenience using a plasmid specific for Leu auxotrophic yeast, signaling pathways, and phenotypes caused by Leu starvation. An accurate understanding of the intracellular responses brought about by Leu auxotrophy can contribute to research in various fields using this model organism and to the understanding of intracellular responses in higher organisms that cannot synthesize Leu.

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Section: Introductionmentioning

confidence: 99%

Response to leucine in Schizosaccharomyces pombe (fission yeast)

Ohtsuka

Shimasaki

Aiba

2022

FEMS Yeast Research

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“…We and others have explored the effects of nutrient limitation, signalling pathways, and gene deletions on the chronological lifespan (CLS) of S. pombe cells, and several ageing-associated proteins have been identified [ 16 – 25 ]. CLS is defined as the time a cell remains viable in a non-dividing state, which mirrors ageing of post-mitotic or quiescent cells in multi-cellular organisms [ 2 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

Barcode sequencing and a high-throughput assay for chronological lifespan uncover ageing-associated genes in fission yeast

Romila¹,

Townsend²,

Małecki³

et al. 2021

Microb Cell

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Ageing-related processes are largely conserved, with simple organisms remaining the main platform to discover and dissect new ageing-associated genes. Yeasts provide potent model systems to study cellular ageing owing their amenability to systematic functional assays under controlled conditions. Even with yeast cells, however, ageing assays can be laborious and resource-intensive. Here we present improved experimental and computational methods to study chronological lifespan in Schizosaccharomyces pombe. We decoded the barcodes for 3206 mutants of the latest gene-deletion library, enabling the parallel profiling of ~700 additional mutants compared to previous screens. We then applied a refined method of barcode sequencing (Bar-seq), addressing technical and statistical issues raised by persisting DNA in dead cells and sampling bottlenecks in aged cultures, to screen for mutants showing altered lifespan during stationary phase. This screen identified 341 long-lived mutants and 1246 short-lived mutants which point to many previously unknown ageing-associated genes, including 46 conserved but entirely uncharacterized genes. The ageing-associated genes showed coherent enrichments in processes also associated with human ageing, particularly with respect to ageing in non-proliferative brain cells. We also developed an automated colony-forming unit assay to facilitate medium- to high-throughput chronological-lifespan studies by saving time and resources compared to the traditional assay. Results from the Bar-seq screen showed good agreement with this new assay. This study provides an effective methodological platform and identifies many new ageing-associated genes as a framework for analysing cellular ageing in yeast and beyond.

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“…On top of these studies, genome-wide screens have provided insights on the role of evolutionarily conserved processes and signalling pathways in ageing such as nutrient response [ 17 , 18 ], protein translation, oxidative damage [ 19 , 20 ], mitochondrial function [ 21 , 22 ] and autophagy [ 22 , 23 ] opening new avenues for biogerontology research. Yeasts have proved informative and helped in understanding mechanisms of highly conserved pathways (from yeast to human) in physiology, health and disease such as the Target of Rapamycin (TOR) [ 24 ], glucose sensing (PKA) and stress response pathways (Sty1/p38) [ 25 ].…”

Section: Introductionmentioning

confidence: 99%

Genome-wide screens in yeast models towards understanding chronological lifespan regulation

Legon

Rallis

2021

Briefings in Functional Genomics

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Cellular models such as yeasts are a driving force in biogerontology studies. Their simpler genome, short lifespans and vast genetic and genomics resources make them ideal to characterise pro-ageing and anti-ageing genes and signalling pathways. Over the last three decades, yeasts have contributed to the understanding of fundamental aspects of lifespan regulation including the roles of nutrient response, global protein translation rates and quality, DNA damage, oxidative stress, mitochondrial function and dysfunction as well as autophagy. In this short review, we focus on approaches used for competitive and non-competitive cell-based screens using the budding yeast Saccharomyces cerevisiae, and the fission yeast Schizosaccharomyces pombe, for deciphering the molecular mechanisms underlying chronological ageing. Automation accompanied with appropriate computational tools allowed manipulation of hundreds of thousands of colonies, generation, processing and analysis of genome-wide lifespan data. Together with barcoding and modern mutagenesis technologies, these approaches have allowed to take decisive steps towards a global, comprehensive view of cellular ageing.

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Genes affecting the extension of chronological lifespan in Schizosaccharomyces pombe (fission yeast)

Cited by 22 publications

References 175 publications

Response to leucine in Schizosaccharomyces pombe (fission yeast)

Response to leucine in Schizosaccharomyces pombe (fission yeast)

Barcode sequencing and a high-throughput assay for chronological lifespan uncover ageing-associated genes in fission yeast

Genome-wide screens in yeast models towards understanding chronological lifespan regulation

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