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Caenorhabditis elegans
24 Downloadable Samples
Affymetrix C. elegans Genome Array (celegans)
Description
Dietary restriction (DR) is the most effective and reproducible intervention to extend lifespan in divergent species1. In mammals, two regimens of DR, intermittent fasting (IF) and caloric restriction (CR), have proven to extend lifespan and reduce the incidence of age-related disorders2. An important characteristic of IF is that it can increase lifespan, even when there is little or no overall decrease in calorie intake2. The molecular mechanisms underlying IF-induced longevity, however, remain largely unknown. Here we establish an IF regimen that effectively extends the lifespan of Caenorhabditis elegans, and show that a nutrient-related signalling molecule, the low molecular weight GTPase Cel-Rheb, has a dual role in lifespan regulation; Cel-Rheb is required for the IF-induced longevity, whereas inhibition of Cel-Rheb mimics the CR effects. We also show that Cel-Rheb exerts its effects in part via the insulin/IGF-like signalling effector DAF-16 in IF, and that Cel-Rheb is required for fasting-induced nuclear translocation of DAF-16. We find that HSP-12.6, a DAF-16 target, functions to mediate the IF-induced longevity. Furthermore, our analyses demonstrate that most of fasting-induced upregulated genes require Cel-Rheb function for their induction, and that Cel-Rheb/Cel-TOR signalling is required for the fasting-induced downregulation of an insulin-like peptide, INS-7. These findings identify the essential role of signalling via Cel-Rheb in IF-induced longevity and gene expression changes, and suggest a molecular link between the IF-induced longevity and the insulin/IGF-like signalling pathway.
Publication Title
Signalling through RHEB-1 mediates intermittent fasting-induced longevity in C. elegans.
Sample Metadata Fields
No sample metadata fields
View Samples- Caenorhabditis elegans
- 6 Downloadable Samples
- Affymetrix C. elegans Genome Array (celegans)
Description
Dietary restriction regimens lead to enhanced stress resistance and extended lifespan in many species through the regulation of fasting and/or diet responsive mechanisms. The fasting stimulus is perceived by sensory neurons and causes behavioral and metabolic adaptations. Several studies have implicated that the nervous system is involved in the regulation of longevity. However, it remains largely unknown whether the nervous system contributes to the regulation of lifespan and/or stress resistance elicited by fasting. In this study, we first investigated the role of the nervous system in fasting-elicited longevity and stress resistance. We found that lifespan extension in Caenorhabditis elegans caused by an intermittent fasting (IF) regimen was suppressed by functional defects in sensory neurons. The IF-induced longevity was also suppressed in a mutant that lacks the enzyme required for the synthesis of an amine neurotransmitter, octopamine (OA), which acts in the absence of food, i.e., under fasting conditions. Although OA administration did not significantly extend the lifespan, it enhanced organismal resistance to oxidative stress. This enhanced resistance was suppressed by a mutation of the OA receptors, SER-3 and SER-6. Moreover, we found that OA administration promoted the nuclear translocation of DAF-16, the key transcription factor in fasting responses, and that the OA-induced enhancement of stress resistance required DAF-16. Altogether, our results suggest that OA signaling, which is triggered by the absence of food, shifts the organismal state to a more protective one to prepare for environmental stresses.
Publication Title
Octopamine enhances oxidative stress resistance through the fasting-responsive transcription factor DAF-16/FOXO in C. elegans.
Sample Metadata Fields
Specimen part
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GSE37305- Caenorhabditis elegans
- 12 Downloadable Samples
- Affymetrix C. elegans Genome Array (celegans)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The Sexual Dimorphism of Dietary Restriction Responsiveness in Caenorhabditis elegans.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Caenorhabditis elegans
- 8 Downloadable Samples
- Affymetrix C. elegans Genome Array (celegans)
Description
Cholesterol has attracted significant attention as a possible lifespan regulator. It has been reported that serum cholesterol levels have an impact on mortality due to age-related disorders such as cardiovascular disease. Diet is also known to be an important lifespan regulator. Dietary restriction retards the onset of age-related diseases and extends lifespan in various organisms. Although cholesterol and dietary restriction are known to be lifespan regulators, it remains to be established whether cholesterol is involved in dietary restriction-induced longevity. Here, we show that cholesterol deprivation suppresses longevity induced by intermittent fasting, which is one of the dietary restriction regimens that effectively extend lifespan. We also found that cholesterol is required for the fasting-induced upregulation of transcriptional target genes such as the insulin/IGF-1 pathway effector DAF-16 and that cholesterol deprivation suppresses the long lifespan of the insulin/IGF-1 receptor daf-2 mutant. Remarkably, we found that cholesterol plays an important role in the fasting-induced nuclear accumulation of DAF-16. Moreover, knockdown of the cholesterol-binding protein NSBP-1, which has been shown to bind to DAF-16 in a cholesterol-dependent manner and to regulate DAF-16 activity, suppresses both fasting-induced longevity and DAF-16 nuclear accumulation. Furthermore, this suppression was not additive to the cholesterol deprivation-induced suppression, which suggests that NSBP-1 mediates, at least in part, the action of cholesterol to promote fasting-induced longevity and DAF-16 nuclear accumulation. These findings identify a novel role for cholesterol in the regulation of lifespan.
Publication Title
Cholesterol regulates DAF-16 nuclear localization and fasting-induced longevity in C. elegans.
Sample Metadata Fields
No sample metadata fields
View Samples- Caenorhabditis elegans
- 4 Downloadable Samples
Description
Many species undergo sexual reproduction to distribute the parental genomes and increase the genomic diversity of the progeny. Among such species, sexual dimorphism is often displayed through morphology, size, behavior, and life-span, depending on the survival and reproduction strategies of the species. The nematode Caenorhabditis elegans has two sexes, hermaphrodite and male, and only the hermaphrodites, which produce both oocytes and sperm, are essential for the perpetuation of the species. In this study, we found that dietary restriction, which is the most reproducible way to retard aging in many species, extends the life-span of C. elegans hermaphrodites but not that of males. Our analysis revealed that fasting induces male-enriched genes in hermaphrodites and that the sex determination pathway affects life-span regulation, even after the completion of development, and is regulated by food availability. Furthermore, fasting activates the entire X-chromosome only in hermaphrodites. Our tiling array analysis identified a fasting-inducible, X-linked non-coding RNA for which expression positively correlated with the activation level of the X-chromosome and longevity. These links between the sex determination mechanism and dietary restriction at multiple levels may give priority to the survival of hermaphrodites during food shortages in C. elegans.
Publication Title
The Sexual Dimorphism of Dietary Restriction Responsiveness in Caenorhabditis elegans.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
STAT1 plays a cental role in the induction of interferon-stimulated genes, but interferon alpha can activate a STAT1-independent pathway that leads to gene expression.
Publication Title
STAT1 is essential for the inhibition of hepatitis C virus replication by interferon-λ but not by interferon-α.
Sample Metadata Fields
Cell line, Treatment
View Samples- Rattus norvegicus
- 6 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
Rat mast cell line RBL-2H3 was analyzed to investigate the molecular mechanism of Dectin-1-mediated activation and responses of mast cells.
Publication Title
Dectin-1-mediated signaling leads to characteristic gene expressions and cytokine secretion via spleen tyrosine kinase (Syk) in rat mast cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Caenorhabditis elegans
- 46 Downloadable Samples
- Affymetrix C. elegans Genome Array (celegans)
Description
Dietary restriction extends lifespan and delays the age-related physiological decline in many species. Intermittent fasting (IF) is one of the most effective dietary restriction regimens that extends lifespan in C. elegans and mammals1,2. In C. elegans, the FOXO transcription factor DAF-16 is implicated in fasting-induced gene expression changes and the longevity response to IF3; however, the mechanisms that sense and transduce fasting-stress stimuli have remained largely unknown. Here we show that a KGB-1/AP1 (activator protein 1) module is a key signalling pathway that mediates fasting-induced transcriptional changes and IF-induced longevity. Our promoter analysis coupled to genome-wide microarray results has shown that the AP-1-binding site, together with the FOXO-binding site, is highly over-represented in the promoter regions of fasting-induced genes. We find that JUN-1 (C. elegans c-Jun) and FOS-1 (C. elegans c-Fos), which constitute the AP-1 transcription factor complex, are required for IF-induced longevity. We also find that KGB-1 acts as a direct activator of JUN-1 and FOS-1, is activated in response to fasting, and, among the three C. elegans JNKs, is specifically required for IF-induced longevity. Our results demonstrate that most fasting-induced upregulated genes, including almost all of the DAF-16-dependent genes, require KGB-1 and JUN-1 function for their induction, and that the loss of kgb-1 suppresses the fasting-induced upregulation of DAF-16 target genes without affecting fasting-induced DAF-16 nuclear translocation. These findings identify the evolutionarily conserved JNK/AP-1 module as a key mediator of fasting-stress responses, and suggest a model in which two fasting-induced signalling pathways leading to DAF-16 nuclear translocation and KGB-1/AP-1 activation, respectively, integrate in the nucleus to coordinately mediate fasting-induced transcriptional changes and IF-induced longevity.
Publication Title
A fasting-responsive signaling pathway that extends life span in C. elegans.
Sample Metadata Fields
Treatment
View Samples- Caenorhabditis elegans
- 10 Downloadable Samples
- Affymetrix C. elegans Genome Array (celegans)
Description
Intermittent fasting is one of the most effective dietary restriction regimens that extend life-span in C. elegans and mammals. Fasting-stimulus responses are key to the longevity response; however, the mechanisms that sense and transduce fasting-stimulus have remained largely unknown. Through a comprehensive transcriptome analysis in C. elegans, we have found that along with the FOXO transcription factor DAF-16, AP-1 (JUN-1/FOS-1) plays a central role in fasting-induced transcriptional changes. KGB-1, one of the C. elegans JNKs, acted as an activator of AP-1, and was activated in response to fasting. KGB-1 and AP-1 were involved in intermittent fasting-induced longevity. Fasting-induced upregulation of the components of the SCF E3 ubiquitin ligase complex via AP-1 and DAF-16 enhanced protein ubiquitination, and reduced protein carbonylation. Our results have thus identified a fasting-responsive KGB-1/AP-1 signaling pathway, which, together with DAF-16, causes transcriptional changes that mediate longevity partly through regulating proteostasis.
Publication Title
A fasting-responsive signaling pathway that extends life span in C. elegans.
Sample Metadata Fields
Treatment
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Activation-induced cytidine deaminase (AID) is essential for the generation of antibody memory but also targets oncogenes among others. We investigated the transcriptional regulation of the AID gene, Aicda, in the class switchinducible CH12F3-2 cells, and found that the Aicda regulation involves derepression by several layers of positive regulatory elements in addition to the 5 promoter region. The 5 upstream region contains functional motifs for the response to signaling by cytokines, CD40-ligand, or stimuli that activate NF-B. The first intron contains functional binding elements for the ubiquitous silencers c-Myb and E2f and for B cellspecific activator Pax5 and E-box-binding proteins.
Publication Title
B cell-specific and stimulation-responsive enhancers derepress Aicda by overcoming the effects of silencers.
Sample Metadata Fields
Specimen part
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