記述言語：英語   出版者・発行元：Advanced Biology  

Yeast is an excellent model organism for research for regulating aging and lifespan, and the studies have made many contributions to date, including identifying various factors and signaling pathways related to aging and lifespan. More than 20 years have passed since molecular biological perspectives are adopted in this research field, and intracellular factors and signal pathways that control aging and lifespan have evolutionarily conserved from yeast to mammals. Furthermore, these findings have been applied to control the aging and lifespan of various model organisms by adjustment of the nutritional environment, genetic manipulation, and drug treatment using low-molecular weight compounds. Among these, drug treatment is easier than the other methods, and research into drugs that regulate aging and lifespan is consequently expected to become more active. Chronological lifespan, a definition of yeast lifespan, refers to the survival period of a cell population under nondividing conditions. Herein, low-molecular weight compounds are summarized that extend the chronological lifespan of Saccharomyces cerevisiae and Schizosaccharomyces pombe, along with their intracellular functions. The low-molecular weight compounds are also discussed that extend the lifespan of other model organisms. Compounds that have so far only been studied in yeast may soon extend lifespan in other organisms.

DOI： 10.1002/adbi.202400138

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記述言語：英語   出版者・発行元：Molecular Microbiology  

In the fission yeast Schizosaccharomyces pombe, the duration of survival in the stationary phase, termed the chronological lifespan (CLS), is affected by various environmental factors and the corresponding gene activities. The ecl family genes were identified in the genomic region encoding non-coding RNA as positive regulators of CLS in S. pombe, and subsequently shown to encode relatively short proteins. Several studies revealed that ecl family genes respond to various nutritional starvation conditions via different mechanisms, and they are additionally involved in stress resistance, autophagy, sexual differentiation, and cell cycle control. Recent studies reported that Ecl family proteins strongly suppress target of rapamycin complex 1, which is a conserved eukaryotic nutrient-sensing kinase complex that also regulates longevity in a variety of organisms. In this review, we introduce the regulatory mechanisms of Ecl family proteins and discuss their emerging findings.

DOI： 10.1111/mmi.15134

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記述言語：英語   出版者・発行元：Journal of Cell Science  

In Schizosaccharomyces pombe, ecl family genes are induced by several signals, such as starvation of various nutrients, including sulfur, amino acids and Mg²⁺, and environmental stress, including heat or oxidative stress. These genes mediate appropriate cellular responses and contribute to the maintenance of cell viability and induction of sexual differentiation. Although this yeast has three ecl family genes with overlapping functions, any environmental conditions that induce ecl3⁺ remain unidentified. We demonstrate that ecl3⁺ is induced by phosphate starvation, similar to its chromosomally neighboring genes, pho1⁺ and pho84⁺, which respectively encode an extracellular acid phosphatase and an inorganic phosphate transporter. ecl3⁺ expression was induced by the transcription factor Pho7 and affected by the cyclin-dependent kinase (CDK)-activating kinase Csk1. Phosphate starvation induced G1 arrest and sexual differentiation via ecl family genes. Biochemical analyses suggested that this G1 arrest was mediated by the stabilization of the CDK inhibitor Rum1, which was dependent on ecl family genes. This study shows that ecl family genes are required for appropriate responses to phosphate starvation and provides novel insights into the diversity and similarity of starvation responses.

DOI： 10.1242/jcs.260759

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記述言語：英語   出版者・発行元：Journal of General and Applied Microbiology  

The fission yeast Schizosaccharomyces pombe ecl family genes respond to various starvation signals and induce appropriate intracellular responses, including the extension of chronological lifespan and induction of sexual differentiation. Herein, we propose that the colonization of hemocoel 1 (COH1) protein of Metarhizium robertsii, an insect-pathogenic fungus, is a functional homolog of S. pombe Ecl1 family proteins.

DOI： 10.2323/jgam.2023.09.001

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CiNii Research

記述言語：英語   出版者・発行元：Microbiologyopen  

The fission yeast Schizosaccharomyces pombe employs two main strategies to adapt to the environment and survive when starved for nutrients. The strategies employ sporulation via sexual differentiation and extension of the chronological lifespan. When a cell is exposed to nutrient starvation in the presence of a cell of the opposite sex, the cells undergo fusion through conjugation and sporulation through meiosis. S. pombe spores are highly resistant to diverse stresses and may survive for a very long time. In this minireview, among the various sexual differentiation processes induced by starvation, we focused on and summarized the findings of the molecular mechanisms of spore formation in fission yeast. Furthermore, comparative measurements of the chronological lifespan of stationary phase cells and G<inf>0</inf> cells and the survival period of spore cells revealed that the spore cells survived for a long period, indicating the presence of an effective mechanism for survival. Currently, many molecules involved in sporulation and their functions are being discovered; however, our understanding of these is not complete. Further understanding of spores may not only deepen our comprehension of sexual differentiation but may also provide hints for sustaining life.

DOI： 10.1002/mbo3.1303

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記述言語：英語   出版者・発行元：Bioscience Biotechnology and Biochemistry  

Tschimganine inhibits growth and extends the chronological lifespan in Schizosaccharomyces pombe. We synthesized a Tschimganine analog, Mochimganine, which extends the lifespan similar to Tschimganine but exhibits a significantly weaker growth inhibition effect. Based on the comparative analysis of these compounds, we propose that Tschimganine has at least 2 targets: one extends the lifespan and the other inhibits growth.

DOI： 10.1093/bbb/zbac051

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記述言語：英語   出版者・発行元：FEMS Yeast Research  

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.

DOI： 10.1093/femsyr/foac020

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記述言語：英語   出版者・発行元：Journal of General and Applied Microbiology  

Fission yeast, Schizosaccharomyces pombe, possesses eight hexose transporters, Ght1~8. In order to clar-ify the role of each hexose transporter on glucose uptake, a glucose uptake assay system was estab-lished and the actual glucose uptake activity of each hexose transporter-deletion mutant was measured. Under normal growth condition containing 2% glucose, ∆ght5 and ∆ght2 mutants showed large and small decrease in glucose uptake activity, respec-tively. On the other hand, the other deletion mutants did not show any decrease in glucose uptake activity indicating that, in the presence of Ght5 and Ght2, the other hexose transporters do not play a significant role in glucose uptake. To understand the relevance between glucose uptake and lifespan regulation, we measured the chronological lifespan of each hexose transporter deletion mutant, and found that only ∆ght5 mutant showed a significant lifespan extension. Based on these results we showed that Ght5 is mainly involved in the glucose uptake in Schizosaccharomyces pombe, and suggested that the ∆ght5 mutant has prolonged lifespan due to physiological changes similar to calorie restriction.

DOI： 10.2323/jgam.2022.05.006

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CiNii Research

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Genes to Cells  

Fission yeast is a good model organism for the study of lifespan. To elucidate the mechanism, we screened for long-lived mutants. We found a nonsense mutation in the ksg1⁺ gene, which encodes an ortholog of mammalian PDK1 (phosphoinositide-dependent protein kinase). The mutation was in the PH domain of Ksg1 and caused defect in membrane localization and protein stability. Analysis of the ksg1 mutant revealed that the reduced amounts and/or activity of the Ksg1 protein are responsible for the increased lifespan. Ksg1 is essential for growth and known to phosphorylate multiple substrates, but the substrate responsible for the long-lived phenotype of ksg1 mutation is not yet known. Genetic analysis showed that deletion of pck2 suppressed the long-lived phenotype of ksg1 mutant, suggesting that Pck2 might be involved in the lifespan extension caused by ksg1 mutation.

DOI： 10.1111/gtc.12897

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：FEMS Yeast Research  

Sulfur is an essential component of various biologically important molecules, including methionine, cysteine and glutathione, and it is also involved in coping with oxidative and heavy metal stress. Studies using model organisms, including budding yeast (Saccharomyces cerevisiae) and fission yeast (Schizosaccharomyces pombe), have contributed not only to understanding various cellular processes but also to understanding the utilization and response mechanisms of each nutrient, including sulfur. Although fission yeast can use sulfate as a sulfur source, its sulfur metabolism pathway is slightly different from that of budding yeast because it does not have a trans-sulfuration pathway. In recent years, it has been found that sulfur starvation causes various cellular responses in S. pombe, including sporulation, cell cycle arrest at G2, chronological lifespan extension, autophagy induction and reduced translation. This MiniReview identifies two sulfate transporters in S. pombe, Sul1 (encoded by SPBC3H7.02) and Sul2 (encoded by SPAC869.05c), and summarizes the metabolic pathways of sulfur assimilation and cellular response to sulfur starvation. Understanding these responses, including metabolism and adaptation, will contribute to a better understanding of the various stress and nutrient starvation responses and chronological lifespan regulation caused by sulfur starvation.

DOI： 10.1093/femsyr/foab041

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Genes to Cells  

There are several examples in the nature wherein the mechanism of longevity control of unicellular organisms is evolutionarily conserved with that of higher multicellular organisms. The present microreview focuses on aging and longevity studies, particularly on chronological lifespan (CLS) concerning the unicellular eukaryotic fission yeast Schizosaccharomyces pombe. In S. pombe, >30 compounds, 8 types of nutrient restriction, and >80 genes that extend CLS have been reported. Several CLS control mechanisms are known to be involved in nutritional response, energy utilization, stress responses, translation, autophagy, and sexual differentiation. In unicellular organisms, the control of CLS is directly linked to the mechanism by which cells are maintained in limited-resource environments, and their genetic information is left to posterity. We believe that this important mechanism may have been preserved as a lifespan control mechanism for higher organisms.

DOI： 10.1111/gtc.12854

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：FEMS Microbiology Letters  

Yeast is a suitable model system to analyze the mechanism of lifespan. In this study, to identify novel factors involved in chronological lifespan, we isolated a mutant with a long chronological lifespan and found a missense mutation in the sur2+ gene, which encodes a homolog of Saccharomyces cerevisiae sphingolipid C4-hydroxylase in fission yeast. Characterization of the mutant revealed that loss of sur2 function resulted in an extended chronological lifespan. The effect of caloric restriction, a well-known signal for extending lifespan, is thought to be dependent on the sur2+ gene.

DOI： 10.1093/femsle/fnab070

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Molecular Microbiology  

So far, more than 70 genes involved in the chronological lifespan (CLS) of Schizosaccharomyces pombe (fission yeast) have been reported. In this mini-review, we arrange and summarize these genes based on the reported genetic interactions between them and the physical interactions between their products. We describe the signal transduction pathways that affect CLS in S. pombe: target of rapamycin complex 1, cAMP-dependent protein kinase, Sty1, and Pmk1 pathways have important functions in the regulation of CLS extension. Furthermore, the Php transcription complex, Ecl1 family proteins, cyclin Clg1, and the cyclin-dependent kinase Pef1 are important for the regulation of CLS extension in S. pombe. Most of the known genes involved in CLS extension are related to these pathways and genes. In this review, we focus on the individual genes regulating CLS extension in S. pombe and discuss the interactions among them.

DOI： 10.1111/mmi.14627

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記述言語：英語   出版者・発行元：Microbiologyopen  

Nutrients including glucose, nitrogen, sulfur, zinc, and iron are involved in the regulation of chronological lifespan (CLS) of yeast, which serves as a model of the lifespan of differentiated cells of higher organisms. Herein, we show that magnesium (Mg²⁺) depletion extends CLS of the fission yeast Schizosaccharomyces pombe through a mechanism involving the Ecl1 gene family. We discovered that ecl1⁺ expression, which extends CLS, responds to Mg²⁺ depletion. Therefore, we investigated the underlying intracellular responses. In amino acid auxotrophic strains, Mg²⁺ depletion robustly induces ecl1⁺ expression through the activation of the general amino acid control (GAAC) pathway—the equivalent of the amino acid response of mammals. Polysome analysis indicated that the expression of Ecl1 family genes was required for regulating ribosome amount when cells were starved, suggesting that Ecl1 family gene products control the abundance of ribosomes, which contributes to longevity through the activation of the evolutionarily conserved GAAC pathway. The present study extends our understanding of the cellular response to Mg²⁺ depletion and its influence on the mechanism controlling longevity.

DOI： 10.1002/mbo3.1176

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1093/bbb/zbac051

Open Access

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1080/27694127.2022.2047442

記述言語：英語   出版者・発行元：Genes to Cells  

Autophagy is an intracellular degradation system widely conserved among various species. Autophagy is induced by the depletion of various nutrients, and this degradation mechanism is essential for adaptation to such conditions. In this study, we demonstrated that sulfur depletion induces autophagy in the fission yeast Schizosaccharomyces pombe. Based on the finding that autophagy induced by sulfur depletion was completely abolished in a mutant in which the ecl1, ecl2 and ecl3 genes were deleted (Δecls), we report that these three genes are essential for the induction of autophagy by sulfur depletion. Furthermore, autophagy-defective mutant cells exhibited poor growth and short lifespan (compared with wild-type cells) under the sulfur-depleted condition. These results indicated that the mechanism of autophagy is necessary for the appropriate adaptation to sulfur depletion.

DOI： 10.1111/gtc.12815

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Bioscience Biotechnology and Biochemistry  

In the longevity research by using yeasts, chronological lifespan is defined as the survival time after entry into stationary phase. Previously, screening for long lived mutants of Schizosaccharomyces pombe was performed to identify the novel factors involved in longevity. From this screening, one long lived mutant called as No.36 was obtained. In this study, we identified the mutation caused in gas1⁺, which encodes glucanosyltransferase (gas1-287 mutation) is responsible for the longevity of No.36 mutant. Through the analysis of this mutant, we found that cell wall perturbing agent micafungin also extends chronological lifespan in fission yeast. This lifespan extension depended on both Pmk1 and Sty1 MAP kinases, and longevity caused by the gas1-287 mutation also depended on these kinases. In summary, we propose that the gas1-287 mutation causes longevity as the similar mechanism as cell wall stress depending on Pmk1 and Sty1 MAPK pathways.

DOI： 10.1080/09168451.2019.1676695

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Molecular Genetics and Genomics  

Many studies show that lifespans of various model organisms can be extended by limiting the quantities of nutrients that are necessary for proliferation. In Schizosaccharomyces pombe, the Ecl1 family genes have been associated with lifespan control and are necessary for cell responses to nutrient depletion, but their functions and mechanisms of action remain uncharacterized. Herein, we show that leucine depletion extends the chronological lifespan (CLS) of leucine-auxotrophic cells. Furthermore, depletion of leucine extended CLS and caused cell miniaturization and cell cycle arrest at the G1 phase, and all of these processes depended on Ecl1 family genes. Although depletion of leucine raises the expression of ecl1⁺ by about 100-fold in leucine-auxotrophic cells, these conditions did not affect ecl1⁺ expression in leucine-auxotrophic fil1 mutants that were isolated in deletion set screens using 79 mutants disrupting a transcription factor. Fil1 is a GATA-type zinc finger transcription factor that reportedly binds directly to the upstream regions of ecl1⁺ and ecl2⁺. Accordingly, we suggest that Ecl1 family genes are induced in response to environmental stresses, such as oxidative stress and heat stress, or by nutritional depletion of nitrogen or sulfur sources or the amino acid leucine. We also propose that these genes play important roles in the maintenance of cell survival until conditions that favor proliferation are restored.

DOI： 10.1007/s00438-019-01592-6

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Genes to Cells  

Most antiaging factors or life span extenders are associated with calorie restriction (CR). Very few of these factors function independently of, or additively with, CR. In this study, we focused on tschimganine, a compound that was reported to extend chronological life span (CLS). Although tschimganine led to the extension of CLS, it also inhibited yeast cell growth. We acquired a Schizosaccharomyces pombe mutant with a tolerance for tschimganine due to the gene crm1. The resulting Crm1 protein appears to export the stress-activated protein kinase Sty1 from the nucleus to the cytosol even under stressful conditions. Furthermore, we synthesized two derivative compounds of tschimganine, α-hibitakanine and β-hibitakanine; these derivatives did not inhibit cell growth, as seen with tschimganine. α-hibitakanine extended the CLS, not only in S. pombe but also in Saccharomyces cerevisiae, indicating the possibility that life span regulation by tschimganine derivative may be conserved across various yeast species. We found that the longevity induced by tschimganine was dependent on the Sty1 pathway. Based on our results, we propose that tschimganine and its derivatives extend CLS by activating the Sty1 pathway in fission yeast, and CR extends CLS via two distinct pathways, one Sty1-dependent and the other Sty1-independent. These findings provide the potential for creating an additive life span extension effect when combined with CR, as well as a better understanding of the mechanism of CLS.

DOI： 10.1111/gtc.12604

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Molecular Microbiology  

Nutritional restrictions such as calorie restrictions are known to increase the lifespan of various organisms. Here, we found that a restriction of sulfur extended the chronological lifespan (CLS) of the fission yeast Schizosaccharomyces pombe. The restriction decreased cellular size, RNA content, and ribosomal proteins and increased sporulation rate. These responses depended on Ecl1 family genes, the overexpression of which results in the extension of CLS. We also showed that the Zip1 transcription factor results in the sulfur restriction-dependent expression of the ecl1⁺ gene. We demonstrated that a decrease in ribosomal activity results in the extension of CLS. Based on these observations, we propose that sulfur restriction extends CLS through Ecl1 family genes in a ribosomal activity-dependent manner.

DOI： 10.1111/mmi.13686

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Molecular Genetics and Genomics  

Overexpression of Ecl1-family genes (ecl1⁺, ecl2⁺, and ecl3⁺) results in the extension of the chronological life span in Schizosaccharomyces pombe. However, the mechanism for this extension has not been defined clearly. Ecl1-family proteins consist of approximately 80 amino acids, and four cysteine residues are conserved in their N-terminal domains. This study focused on the Ecl1 protein, mutating its cysteine residues sequentially to confirm their importance. As a result, all mutated Ecl1 proteins nearly lost the function to extend the chronological life span, suggesting that these four cysteine residues are essential for the Ecl1 protein. Utilizing ICP-AES (inductively coupled plasma atomic emission spectroscopy) analysis, we found that wild-type Ecl1 proteins contain zinc, while cysteine-mutated Ecl1 proteins do not. We also analyzed the effect of environmental zinc on the chronological life span. We found that zinc limitation extends the chronological life span, and this extension depends on the Ecl1-family proteins.

DOI： 10.1007/s00438-016-1285-x

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DOI： 10.1007/s00438-014-0845-1

開催年月日： 2020年9月

会議種別：口頭発表（一般）  

開催地：Web開催   国名：日本国  

開催年月日： 2020年9月

記述言語：日本語   会議種別：ポスター発表  

開催地：Web開催   国名：日本国  

開催年月日： 2020年9月

記述言語：日本語   会議種別：ポスター発表  

開催地：Web開催   国名：日本国  

開催年月日： 2020年9月

記述言語：日本語   会議種別：ポスター発表  

開催地：Web開催   国名：日本国  

開催年月日： 2020年9月

記述言語：日本語   会議種別：ポスター発表  

開催地：Web開催   国名：日本国  

開催年月日： 2020年3月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：名古屋   国名：日本国  

開催年月日： 2020年3月

記述言語：日本語   会議種別：ポスター発表  

開催地：名古屋   国名：日本国  

開催年月日： 2020年3月

記述言語：日本語   会議種別：ポスター発表  

開催地：名古屋   国名：日本国  

開催年月日： 2020年3月

記述言語：日本語   会議種別：ポスター発表  

開催地：名古屋   国名：日本国  

開催年月日： 2019年12月

記述言語：日本語   会議種別：ポスター発表  

開催地：福岡   国名：日本国  

開催年月日： 2019年9月

記述言語：日本語   会議種別：ポスター発表  

開催地：静岡市清水文化会館マリナート  

開催年月日： 2019年9月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：静岡市清水文化会館マリナート   国名：日本国  

開催年月日： 2019年7月

記述言語：英語   会議種別：ポスター発表  

開催地：Barcelona, Spain   国名：スペイン