Caenorhabditis elegans
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA340183 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR4066103.fastq.gz | Fastqsanger.gz | |||
| SRR4066104.fastq.gz | Fastqsanger.gz | |||
| SRR4066105.fastq.gz | Fastqsanger.gz | |||
| SRR4066106.fastq.gz | Fastqsanger.gz |
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Project description:Insulin/IGF-1 Signaling (IIS) is known to constrain longevity by inhibiting the transcription factor FOXO. How phosphorylation mediated by IIS kinases regulates lifespan beyond FOXO remains unclear. Here, we profile IIS-dependent phosphorylation changes in a large-scale quantitative phosphoproteomic analysis of wild-type and three IIS mutant Caenorhabditis elegans strains. We quantify more than 15,000 phosphosites and find that 476 of these are differentially phosphorylated in the long-lived daf-2/insulin receptor mutant. We develop a machine learning-based method to prioritize 25 potential lifespan-related phosphosites. We perform validations to show that AKT-1 pT492 inhibits DAF-16/FOXO and compensates the loss of daf-2 function, that EIF-2α pS49 potently inhibits protein synthesis and daf-2 longevity, and that reduced phosphorylation of multiple germline proteins apparently transmits reduced DAF-2 signaling to the soma. In addition, an analysis of kinases with enriched substrates detects that casein kinase 2 (CK2) subunits negatively regulate lifespan. Our study reveals detailed functional insights into longevity.
2021-06-10 | PXD020440 |
Project description:The nuclear chromatin landscape changes with age – a phenomenon observed across many species, including humans. Notably, perturbing this landscape can alter the rate of aging, indicating at least a partial role in controlling this process. This raises the question of whether chromatin alterations also distinguish animals that age at unusual rates. To explore this, we focused on insulin/IGF-like signaling (IIS) in Caenorhabditis elegans, a well-characterized signaling pathway whose impairment drastically slows aging and extends lifespan of these animals. Specifically, we conducted ATAC- and mRNA-seq in animals with reduced IIS (i.e., daf-2 mutants). Interestingly, we found that enhancer regions tend to close and become transcriptionally repressed with age, but under reduced IIS, they tend to open and become transcriptionally active, suggesting their potential relevance for lifespan regulation. By screening transcription factors (TFs) predicted to bind these regions, we identified the HOX gene LIN-39 as a novel aging-preventive TF required for the longevity of daf-2 mutants. LIN-39 performs this role specifically during development and in neurons. Further investigation showed that LIN-39 was acting around the L3 larval stage and in the hermaphrodite-specific VC class of cholinergic motor neurons – at a time when they undergo maturation. Finally, this LIN-39-dependent longevity required DAF-16/FOXO, a well-established aging-preventive TF that acts downstream of DAF-2, which may synergize with LIN-39 in VC neurons to open enhancer the regions. We ultimately propose a model whereby longevity of daf-2 mutant hermaphrodites requires a longevity-promoting signal emitted by VC neurons – a signal that relies on correct VC neuron maturation around the L3 stage, which in turn is assured by the actions of LIN-39 and resulting chromatin and gene expression changes. This renders LIN-39 a rare example of a developmental determinant of longevity. And given the conservation of IIS, HOX and FOXO TFs, and cholinergic neuron function across species, the here described mechanism may reflect a general principle by which developmental transcriptional programs shape adult longevity.
2025-05-29 | GSE271972 | GEO
Project description:The nuclear chromatin landscape changes with age – a phenomenon observed across many species, including humans. Notably, perturbing this landscape can alter the rate of aging, indicating at least a partial role in controlling this process. This raises the question of whether chromatin alterations also distinguish animals that age at unusual rates. To explore this, we focused on insulin/IGF-like signaling (IIS) in Caenorhabditis elegans, a well-characterized signaling pathway whose impairment drastically slows aging and extends lifespan of these animals. Specifically, we conducted ATAC- and mRNA-seq in animals with reduced IIS (i.e., daf-2 mutants). Interestingly, we found that enhancer regions tend to close and become transcriptionally repressed with age, but under reduced IIS, they tend to open and become transcriptionally active, suggesting their potential relevance for lifespan regulation. By screening transcription factors (TFs) predicted to bind these regions, we identified the HOX gene LIN-39 as a novel aging-preventive TF required for the longevity of daf-2 mutants. LIN-39 performs this role specifically during development and in neurons. Further investigation showed that LIN-39 was acting around the L3 larval stage and in the hermaphrodite-specific VC class of cholinergic motor neurons – at a time when they undergo maturation. Finally, this LIN-39-dependent longevity required DAF-16/FOXO, a well-established aging-preventive TF that acts downstream of DAF-2, which may synergize with LIN-39 in VC neurons to open enhancer the regions. We ultimately propose a model whereby longevity of daf-2 mutant hermaphrodites requires a longevity-promoting signal emitted by VC neurons – a signal that relies on correct VC neuron maturation around the L3 stage, which in turn is assured by the actions of LIN-39 and resulting chromatin and gene expression changes. This renders LIN-39 a rare example of a developmental determinant of longevity. And given the conservation of IIS, HOX and FOXO TFs, and cholinergic neuron function across species, the here described mechanism may reflect a general principle by which developmental transcriptional programs shape adult longevity.
2025-05-29 | GSE271970 | GEO
Project description:Many tissue-specific stem cells maintain the ability to produce multiple cell types during long periods of non-division, or quiescence. FOXO transcription factors promote quiescence and stem cell maintenance, but the mechanisms by which FOXO proteins promote multipotency during quiescence are still emerging. The single FOXO ortholog in C. elegans, daf-16, promotes entry into a quiescent and stress-resistant larval stage called dauer in response to adverse environmental cues. During dauer, stem and progenitor cells maintain or re-establish multipotency to allow normal development to resume after dauer. We find that during dauer, daf-16/FOXO prevents epidermal stem cells (seam cells) from prematurely adopting differentiated, adult characteristics. In particular, dauer larvae that lack daf-16 misexpress collagens that are normally adult-enriched. Using col-19p::gfp as an adult cell fate marker, we find that all major daf-16 isoforms contribute to opposing col-19p::gfp expression during dauer. By contrast, daf-16(0) larvae that undergo non-dauer development do not misexpress col-19p::gfp. Adult cell fate and the timing of col-19p::gfp expression are regulated by the heterochronic gene network, including lin-41 and lin-29. lin-41 encodes an RNA-binding protein orthologous to LIN41/TRIM71 in mammals, and lin-29 encodes a conserved zinc finger transcription factor. In non-dauer development lin-41 opposes adult cell fate by inhibiting the translation of lin-29, which directly activates col-19 transcription and promotes adult cell fate. We find that during dauer, lin-41 blocks col-19p::gfp expression, but surprisingly, lin-29 is not required in this context. Additionally, daf-16 promotes the expression of lin-41 in dauer larvae. The col-19p::gfp misexpression phenotype observed in dauer larvae with reduced daf-16 requires the downregulation of lin-41, but does not require lin-29. Taken together, this work demonstrates a novel role for daf-16/FOXO as a heterochronic gene that promotes expression of lin-41/TRIM71 to contribute to multipotent cell fate in a quiescent stem cell model.
2021-10-09 | GSE179166 | GEO
Project description:FoxO transcription factors can promote longevity in invertebrates and mammals. In C.elegans, the FoxO family member DAF-16 is required for lifespan extension in the contexts of daf-2/IGFR mutation and germline ablation. The daf-16 genomic locus encodes three distinct groups of transcripts (a,b, and d/f/h). In animals with reduced insulin signaling or ablated germlines, mutations that reduce daf-16a and d/f/h levels without affecting daf-16b reduce lifespan to the same extent as daf-16 null mutations. We reasoned that identifying a set of targets of the daf-16a and d/f/h isoforms that are differentially regulated in two contexts of reduced insulin signaling and in germline ablated animals would enrich for the daf-16 transcriptional targets that are required for longevity. We identified targets that were differentially regulated in daf-2(e1368) and daf-2(e1370) mutants relative to wild-type, and differentially regulated in the opposite direction from WT in compound mutants with both daf-16(mg54), which eliminates the a and d/f/h isoforms, and daf-16(mu86) which is a predicted null allele. We performed a similar analysis in glp-1(e2141) germline ablated animals (omitting the wild-type comparison). We then identified daf-16 targets associated with longevity (dal genes) which were found in all three sets of comparisons.
2019-03-01 | GSE111338 | GEO
Project 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.
2008-12-15 | GSE9682 | GEO
Project description:Investigation of whole genome gene expression level changes in C. elegans rsks-1, daf-2, daf-2 rsks-1 and daf-16; daf-2 rsks-1 mutant compared to the wild-type N2 strain. The mutants have altered longevity phenotypes. The mutants analyzed in this study are further described in Di Chen, Patrick Wai-Lun Li, Benjamin A. Goldstein, Waijiao Cai, Emma Lynn Thomas, Fen Chen, Alan E. Hubbard, Simon Melov and Pankaj Kapahi, Germline Signaling Mediates the Synergistically Prolonged Longevity by Double Mutations in daf-2 and rsks-1 in C. elegans, Cell Reports (CELL-REPORTS-D-13-00388).
2013-11-14 | GSE52340 | GEO
Project description:Investigation of whole genome gene expression level changes in C. elegans rsks-1, daf-2, daf-2 rsks-1 and daf-16; daf-2 rsks-1 mutant compared to the wild-type N2 strain. The mutants have altered longevity phenotypes. The mutants analyzed in this study are further described in Di Chen, Patrick Wai-Lun Li, Benjamin A. Goldstein, Waijiao Cai, Emma Lynn Thomas, Fen Chen, Alan E. Hubbard, Simon Melov and Pankaj Kapahi, Germline Signaling Mediates the Synergistically Prolonged Longevity by Double Mutations in daf-2 and rsks-1 in C. elegans, Cell Reports (CELL-REPORTS-D-13-00388). A 47 chip study using total RNAs from C. elegans wild-type N2 (9 replicates), rsks-1 mutant (9 replicates), daf-2 mutant (9 replicates), daf-2 rsks-1 double mutant (10 replicates) and daf-16; daf-2 rsks-1 triple mutant (10 replicates) measured gene expression levels at the whole genome level.
2013-11-14 | E-GEOD-52340 | biostudies-arrayexpress
Project description:The homeostatic maintenance of the genomic DNA is crucial for regulating aging processes. However, the role of RNA homeostasis in aging processes remains unknown. RNA helicases are a large family of enzymes that regulate the biogenesis and homeostasis of RNA. However, the functional significance of RNA helicases in aging has not been explored. Here, we report that a large fraction of RNA helicases regulate the lifespan ofCaenorhabditis elegans. In particular, we show that a DEAD-box RNA helicase, helicase 1 (HEL-1), promotes longevity by specifically activating the DAF-16/forkhead box O (FOXO) transcription factor signaling pathway. We find that HEL-1 is required for the longevity conferred by reduced insulin/insulin-like growth factor 1 (IGF-1) signaling (IIS) and is sufficient for extending lifespan. We further show that the expression of HEL-1 in the intestine and neurons contributes to longevity. HEL-1 enhances the induction of a large fraction of DAF-16 target genes. Thus, the RNA helicase HEL-1 appears to promote longevity in response to decreased IIS as a transcription coregulator of DAF-16. Because HEL-1 and IIS are evolutionarily well conserved, a similar mechanism for longevity regulation via an RNA helicase-dependent regulation of FOXO signaling may operate in mammals, including humans.
2023-10-04 | GSE244493 | GEO
Project description:Cholesterol regulates DAF-16 nuclear localization and fasting-induced longevity in C. elegans
| PRJNA219742 | ENA