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C. elegans daf2 mutant adults

ABSTRACT: Analysis of gene expression in long-lived daf-2 mutants for the insulin/IGF-1 receptor. daf-2(e1370) and daf-2(m577) alleles each examined as single and as double mutations with the daf-16(df50) allele. DAF-2 regulates DAF-16, a transcription factor. Results provide insight into longevity. Keywords: other

ORGANISM(S): Caenorhabditis elegans

PROVIDER: GSE1762 | GEO | 2004/09/14

SECONDARY ACCESSION(S): PRJNA90521

REPOSITORIES: GEO

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Transcription profiling of C. elegans long luved daf-2 mutants for the insulin/IGF-1 receptor. daf-2(e1370) and daf-2(m577) alleles each examined as single and as double mutations with the daf-16(df50) reveals insights into longevity

Project description:Analysis of gene expression in long-lived daf-2 mutants for the insulin/IGF-1 receptor. daf-2(e1370) and daf-2(m577) alleles each examined as single and as double mutations with the daf-16(df50) allele. DAF-2 regulates DAF-16, a transcription factor. Results provide insight into longevity.

2007-07-05 | E-GEOD-1762 | biostudies-arrayexpress

Transcription profiling of long-lived C.elegans daf-2 pathway mutants with wild type/short-lived mutants

Project description:Comparison of long-lived daf-2 pathway mutants with wild type/short-lived mutants. A: age-1 fer-15; fem-1 vs. fer-15; fem-1. B: age-1 fer-15; fem-1 vs. fer-15; fem-1. C: fer-15; daf-2(mu150); fem-1 vs. fer-15; fem-1. D: fer-15; daf-2(mu150); fem-1 vs. fer-15; fem-1. E: daf-16::gfp in daf-16(mu86);daf-2(e1370) vs. daf-16(mu86);daf-2(e1370). F: daf-2(e1368); fer-15; fem-1 vs. fer-15; fem-1. G: fer-15; daf-2(mu150); fem-1 vs. fer-15; fem-1. H: age-1 fer-15; fem-1 vs. fer-15; fem-1. I: fer-15; daf-2(mu150); fem-1 vs. fer-15; fem-1. J: daf-16::gfp in daf-2(e1370); daf-16(mu86) vs. daf-2(e1370); daf-16(mu86). K: daf-2(mu150) vs. wild type. L: daf-2(e1370) vs. daf-2(e1370); daf-16(mu86). M: daf-2(e1370) vs. daf-2(e1370); daf-16(mu86). N: daf-2(e1370) vs. daf-2(e1370); daf-16(mu86).

2003-07-17 | E-MEXP-7 | biostudies-arrayexpress

Divergent mechanisms controlling hypoxic sensitivity and lifespan by the DAF-2/Insulin/IGF-receptor pathway

Project description:To identify genes that selectively regulate hypoxic sensitivity, we compared the whole-organismal transcriptomes of three daf-2 reduction-of-function alleles, all of which are hypoxia resistant, thermotolerant, and long lived but differ in their rank of severities for these phenotypes. The transcript levels of 172 genes were increased in the most hypoxia resistant daf-2 allele, e1370, relative to the other alleles whereas transcripts from only 10 genes were decreased in abundance.

2009-10-31 | GSE18601 | GEO

Endogenous DAF-16 genome-wide recruitment under low Insulin signalling condition in Caenorhabditis elegans

Project description:In order to understand the complexity of gene regulation downstream of IIS, we did RNA-seq in mixed culture in wild-type, daf-2(e1370), daf-16(mgDf50);daf-2(e1370) and daf-2(e1370);daf-12(m20 and correlated it with ChIP-seq data

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RNA sequencing analysis of DAF-16 target gene expression when math-33 function is genetically inactivated

Project description:In this study we have investigated the effect of loss of math-33 activity on DAF-16-mediated target gene regulation in C. elegans under conditions of reduced Insulin/IGF-1 signaling (IIS). Using whole nematode RNA sequencing experiments we found that the daf-2(e1370)-mediated induction and repression of DAF-16 target genes was decreased in daf-2(e1370); math-33(tm3561) mutant animals. Our data suggest that the downregulation of endogenous DAF-16 isoforms in the absence of a functional MATH-33 severely affects the global expression of DAF-16 targets when IIS activity is reduced. Therefore, MATH-33 is essential for DAF-16-mediated target gene activation and repression in the context of IIS. DAF-16 mediated target gene regulation was analyzed in daf-2(e1370) nematodes and compared to daf-2(e1370); math-33(tm3561) mutant animals. daf-16(mu86); daf-2(e1370); N2 (wild type) and math-33(tm3561) single mutant animals were used as controls.

2016-06-22 | E-GEOD-70117 | biostudies-arrayexpress

Insulin Signaling Regulates Longevity Through Protein Phosphorylation in Caenorhabditis elegans

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 |

RNA sequencing analysis of DAF-16 target gene expression when math-33 function is genetically inactivated

2016-06-22 | GSE70117 | GEO

Defining changes in the total levels of proteins during aging of C. elegans

Project description:We performed label-free proteomics in C. elegans to define and quantify changes in the ubiquitinated (Ub)-proteome during the aging process. More specifically, we compared wild-type worms at the first day of adulthood with young (day 5), mid-age (day 10) and aged adults (day 15). Moreover, we assessed protein levels of age-matched long-lived genetic models of dietary restriction (eat-2(ad1116)) and reduced insulin/IGF-1 signaling (daf-2(e1370)).

2021-05-26 | PXD025128 | Pride

daf-16/FoxO isoform-specific deletion mutants

Project description:FoxO transcription factors promote longevity across taxa. How they do so is poorly understood. In the nematode Caenorhabditis elegans, the A- and F-isoforms of the FoxO transcription factor DAF-16 extend life span in the context of reduced DAF-2 insulin-like growth factor receptor (IGFR) signaling. To elucidate the mechanistic basis for DAF-16/FoxO-dependent life span extension, we performed an integrative analysis of isoform-specific daf-16/FoxO mutants. In contrast to previous studies suggesting that DAF-16F plays a more prominent role in life span control than DAF-16A, isoform-specific daf-16/FoxO mutant phenotypes and whole transcriptome profiling revealed a predominant role for DAF-16A over DAF-16F in life span control, stress resistance, and target gene regulation. Integration of these data sets enabled the prioritization of a subset of 92 DAF-16/FoxO target genes for functional interrogation. Among 29 genes tested, two DAF-16A-specific target genes significantly influenced longevity. Our discovery of new longevity genes underscores the efficacy of our integrative strategy while providing a general framework for identifying specific downstream gene regulatory events that contribute substantially to transcription factor functions. As FoxO transcription factors have conserved functions in promoting longevity and may be dysregulated in aging-related diseases, these findings promise to illuminate fundamental principles underlying aging in animals. Whole-transcriptome profiling of daf-16/FoxO isoform-specific deletion mutants in the long-lived daf-2(e1370) background. Included are daf-16 wild-type, daf-16 null mutation, daf-16a/f mutation, two independent daf-16a mutations, and daf-16f mutation. N2 wild-type controls are also included.

2015-08-27 | E-GEOD-72426 | biostudies-arrayexpress

Identification of DAF-16/FoxO targets associated with longevity

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

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