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Gene expression by myriocin treatment

ABSTRACT: Studies of aging and longevity are revealing how diseases that shorten life can be controlled to improve the quality of life and lifespan itself. Two strategies under intense study to accomplish this goal are rapamycin treatment and calorie restriction. New strategies are being discovered including one that uses low-dose myriocin treatment. Myriocin inhibits the first enzyme in sphingolipid synthesis in all eukaryotes and we showed recently that low-dose myriocin treatment increases yeast lifespan at least in part by down-regulating the sphingolipid-controlled Pkh1/2-Sch9 (ortholog of mammalian S6 kinase) signaling pathway. Here we show that myriocin treatment has global influences and modulates the evolutionarily conserved Snf1/AMPK, PKA and TORC1 signaling pathways to enhance yeast lifespan. These extensive affects of myriocin rival those of rapamycin and calorie restriction. Our studies in yeast along with other studies in mammals reveal the potential of myriocin or related compounds to lower the incidence of age-related diseases in humans.

ORGANISM(S): Schizosaccharomyces pombe Saccharomyces cerevisiae

PROVIDER: GSE41362 | GEO | 2014/09/22

SECONDARY ACCESSION(S): PRJNA176689

REPOSITORIES: GEO

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Gene expression by myriocin treatment

Project description:Studies of aging and longevity are revealing how diseases that shorten life can be controlled to improve the quality of life and lifespan itself. Two strategies under intense study to accomplish this goal are rapamycin treatment and calorie restriction. New strategies are being discovered including one that uses low-dose myriocin treatment. Myriocin inhibits the first enzyme in sphingolipid synthesis in all eukaryotes and we showed recently that low-dose myriocin treatment increases yeast lifespan at least in part by down-regulating the sphingolipid-controlled Pkh1/2-Sch9 (ortholog of mammalian S6 kinase) signaling pathway. Here we show that myriocin treatment has global influences and modulates the evolutionarily conserved Snf1/AMPK, PKA and TORC1 signaling pathways to enhance yeast lifespan. These extensive affects of myriocin rival those of rapamycin and calorie restriction. Our studies in yeast along with other studies in mammals reveal the potential of myriocin or related compounds to lower the incidence of age-related diseases in humans. No-myriocin-treated cells and myriocin-treated cells; three biological replicates in each treatment

2014-09-22 | E-GEOD-41362 | biostudies-arrayexpress

The Gcn4 Transcription Factor Reduces Protein Synthesis Capacity and Extends Yeast Lifespan [RNA-Seq]

Project description:In Saccharomyces cerevisiae, deletion of genes encoding proteins of the large ribosomal subunit (RPLs) increases the replicative lifespan in a Gcn4-dependent manner. However, how Gcn4, a key transcriptional activator of amino acid biosynthesis genes, increases lifespan, is unknown. Here we show that Gcn4 acts as a repressor of protein synthesis. By analyzing the mRNA and protein abundance, the ribosome occupancy and protein synthesis rate in various yeast strains, we demonstrate that Gcn4 is sufficient to reduce protein synthesis and to increase yeast lifespan. Chromatin immunoprecipitation reveals Gcn4 binding not only at genes that are activated, but also at genes that are repressed upon Gcn4 overexpression. The promoters of repressed genes contain Rap1 binding motifs. Our data suggest that Gcn4 is a central regulator of protein synthesis under multiple perturbations - including ribosomal protein (RP) gene deletions, calorie restriction, rapamycin treatment - and provide an explanation for its role in longevity and stress response.

2017-06-28 | GSE85590 | GEO

The Gcn4 Transcription Factor Reduces Protein Synthesis Capacity and Extends Yeast Lifespan [ChIP-Seq]

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The Gcn4 Transcription Factor Reduces Protein Synthesis Capacity and Extends Yeast Lifespan

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Calorie/Dietary Restriction and Resveratrol in Female Drosophila Melanogaster Head/Thorax

2011-07-21 | GSE26724 | GEO

TORC1 signaling pathway inhibition by rapamycin and caffeine affect lifespan, global gene expression and cell proliferation of fission yeast

Project description:Target of rapamycin complex 1 (TORC1) is implicated in growth control and aging from yeast to humans. Fission yeast is emerging as a popular model organism to study TOR signaling, although rapamycin has been thought to not affect cell growth in this organism. Here we analyzed the effects of rapamycin and caffeine, singly and combined, on multiple cellular processes in fission yeast. The two drugs led to diverse and specific phenotypes that depended on TORC1 signaling pathway inhibition, including prolonged chronological lifespan, inhibition of global translation, inhibition of cell growth and division, and reprogramming of global gene expression mimicking nitrogen starvation. Rapamycin and caffeine differentially affected these various TORC1-dependent processes. Combined drug treatment augmented most phenotypes and effectively blocked cell growth. Although rapamycin showed a much more subtle effect on global translation than did caffeine, rapamycin was more effective in prolonging chronological lifespan. Rapamycin prolonged the lifespan of non-growing cells only when applied during the growth phase but not when applied after cells had stopped proliferation. The doses of rapamycin and caffeine strongly correlated with growth inhibition and with lifespan extension. This comprehensive analysis will inform future studies into TORC1 function and cellular aging in fission yeast and beyond.

2013-05-05 | E-MTAB-1489 | biostudies-arrayexpress

Calorie/Dietary Restriction and Resveratrol in Female Drosophila Melanogaster Head/Thorax

Project description:Feeding resveratrol to Drosophila melanogaster extends lifespan. Studies of microarray show similarities between calorie/dietary restriction and resveratrol on both a gene expression and biological pathway level. 9 samples: 3 biological replicates each of normal diet, restricted diet and normal diet plus resveratrol

2011-07-20 | E-GEOD-26724 | biostudies-arrayexpress

Calorie restriction and calorie dilution have different impacts on body fat, metabolism, behavior and hypothalamic gene expression

Project description:Caloric restriction is a robust intervention to increase life span. Giving less food (CR), or allowing free access to diluted diet with indigestible components (CD) are two methods to impose restriction. CD does not generate the same lifespan effect as CR. We compared responses of C57BL/6 mice to equivalent levels of CR and CD. Our study calorie restriction and calorie two restriction methods different effect on hypothamic gene expression pattern, RNA-seq was performed using hypothalamus of mice with 2 methods treatment as well as control group.

2022-05-17 | GSE200820 | GEO

Expression data from dietary restricted budding yeast

Project description:Dietary restriction (also known as caloric/calorie restriction; CR) extends the lifespan of species from all three eukaryotic kingdoms. The restriction of the diet interferes directly with the aging process by triggering a tightly controlled genetic program where specific sets of genes are either upregulated downreguled. We used microarray-technology to detail the global program of gene expression underlying the anti-aging effect of dietary restriction and identified distinct classes of up- and down-regulated genes. In order to apply dietary restriction in budding yeast we cultured cells on a reduced glucose medium (0.5% vs. 2.0%), which is known as moderate DR regimen. We then compared mRNA expression of yeast cells cultured under dietary restricted (0.5% glucose) and ad libitum (2.0% glucose) conditions.

2012-06-20 | E-GEOD-38635 | biostudies-arrayexpress

Gene expression changes in yeast cells deleted for Nat4 and cells grown in calorie-restriction

Project description:We report here mRNA-seq data of wild-type and Nat4-deletion mutant yeast cells. We also report mRNA-seq data of wild-type yeast cells grown under non-calorie restriction (NCR) and calorie restriction (CR) conditions.

2016-11-22 | GSE86242 | GEO

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