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Reduced insulin/IGF-1-like signaling restores germ cell immortality in Caenorhabditis elegans Piwi mutants

ABSTRACT: Reduced insulin/IGF-1-like signaling restores germ cell immortality in Caenorhabditis elegans Piwi mutants

PROVIDER: PRJNA174368 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR553522.fastq.gz	Fastqsanger.gz
	SRR553523.fastq.gz	Fastqsanger.gz
	SRR553524.fastq.gz	Fastqsanger.gz
	SRR553525.fastq.gz	Fastqsanger.gz

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Reduced insulin/IGF-1 signaling restores germ cell immortality to Caenorhabditis elegans Piwi mutants.

Project description:Defects in the Piwi/piRNA pathway lead to transposon desilencing and immediate sterility in many organisms. We found that the C. elegans Piwi mutant prg-1 became sterile after growth for many generations. This phenotype did not occur for RNAi mutants with strong transposon-silencing defects and was separable from the role of PRG-1 in transgene silencing. Brief periods of starvation extended the transgenerational lifespan of prg-1 mutants by stimulating the DAF-16/FOXO longevity transcription factor. Constitutive activation of DAF-16 via reduced daf-2 insulin/IGF-1 signaling immortalized prg-1 strains via RNAi proteins and histone H3 lysine 4 demethylases. In late-generation prg-1 mutants, desilencing of repetitive segments of the genome occurred, and silencing of repetitive loci was restored in prg-1; daf-2 mutants. This study reveals an unexpected interface between aging and transgenerational maintenance of germ cells, where somatic longevity is coupled to a genome-silencing pathway that promotes germ cell immortality in parallel to the Piwi/piRNA system.

| S-EPMC4049074 | biostudies-literature

Reduced insulin/IGF-1-like signaling restores germ cell immortality in Caenorhabditis elegans Piwi mutants

Project description:This SuperSeries is composed of the SubSeries listed below.

2013-06-01 | GSE40573 | GEO

Reduced insulin/IGF-1-like signaling restores germ cell immortality in Caenorhabditis elegans Piwi mutants

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2013-06-01 | E-GEOD-40573 | biostudies-arrayexpress

Reduced insulin/IGF-1 signaling restores the dynamic properties of key stress granule proteins during aging

Project description:Low complexity “prion-like” domains in key RNA-binding proteins (RBPs) mediate the reversible assembly of RNA granules. Individual RBPs harboring these domains have been linked to specific neurodegenerative diseases. Although their aggregation in neurodegeneration has been extensively characterized, it remains unknown how the process of aging disturbs RBP dynamics. We show that a wide variety of RNA granule components including stress granule proteins become highly insoluble with age in C. elegans and that reduced insulin/IGF-1 daf-2 receptor signaling efficiently prevents their aggregation. Importantly, stress granule-related RBP aggregates are associated with reduced fitness. We show that HSF-1 is a main regulator of stress granule-related RBP aggregation in both young and aged animals. During aging, increasing DAF-16 activity restores dynamic stress granule-related RBPs partly by reducing the build-up of other misfolded proteins that seed RBP aggregation. Longevity-associated mechanisms found to maintain dynamic RBPs during aging could be relevant for neurodegenerative diseases.

2017-01-16 | PXD003451 | Pride

Circulating insulin-like growth factor (IGF)-1 Regulates Hippocampal IGF-1 Levels and Brain Gene Expression During Adolescence

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Reduced Insulin/IGF-1 Signaling Restores the Dynamic Properties of Key Stress Granule Proteins during Aging.

Project description:Low-complexity "prion-like" domains in key RNA-binding proteins (RBPs) mediate the reversible assembly of RNA granules. Individual RBPs harboring these domains have been linked to specific neurodegenerative diseases. Although their aggregation in neurodegeneration has been extensively characterized, it remains unknown how the process of aging disturbs RBP dynamics. We show that a wide variety of RNA granule components, including stress granule proteins, become highly insoluble with age in C. elegans and that reduced insulin/insulin-like growth factor 1 (IGF-1) daf-2 receptor signaling efficiently prevents their aggregation. Importantly, stress-granule-related RBP aggregates are associated with reduced fitness. We show that heat shock transcription factor 1 (HSF-1) is a main regulator of stress-granule-related RBP aggregation in both young and aged animals. During aging, increasing DAF-16 activity restores dynamic stress-granule-related RBPs, partly by decreasing the buildup of other misfolded proteins that seed RBP aggregation. Longevity-associated mechanisms found to maintain dynamic RBPs during aging could be relevant for neurodegenerative diseases.

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Regulation of germline proteostasis by insulin/IGF-1 signaling

Project description:Gametogenesis involves active protein synthesis and heavily relies on proteostasis. How animals regulate germline proteostasis at the organismal level is poorly understood. Our recent work in C. elegans indicates that germline development requires coordinated activities between insulin/IGF-1 signaling and HSF-1, the transcriptional activator of many molecular chaperones in stress and physiological conditions. In this study, we show that HSF-1 is important for germline proteostasis at ambient temperature. Depletion of HSF-1 from germ cells impairs chaperone gene expression, causing protein degradation and aggregation and, consequently, declines in fecundity and gamete quality. Reduced insulin/IGF-1 signaling confers germ cells' tolerance to limited protein folding capacity and proteotoxic stress by lowering ribosome biogenesis and translation. Interestingly, regulation of germline proteostasis by insulin/IGF-1 signaling occurs non-cell-autonomously. Our data suggest that insulin/IGF-1 signaling controls the expression of the evolutionarily conserved intestinal peptide transporter PEPT-1 via its downstream transcription factor FOXO/DAF-16, therefore allowing dietary proteins to be incorporated into an amino acid pool that fuels ribosomal biogenesis and translation in the germline. We propose that this pathway plays a critical role in regulating germline protein synthesis, which must be at balance with HSF-1-dependent protein folding to achieve proteostasis in gametogenesis.

2024-05-20 | GSE256186 | GEO

Circulating insulin-like growth factor (IGF)-1 Regulates Hippocampal IGF-1 Levels and Brain Gene Expression During Adolescence

Project description:This study, using a growth hormone (GH)-deficient dwarf animal model and peripheral GH replacement, investigated the effects of circulating IGF-1 during adolescence on IGF-1 levels in the brain. Our results demonstrated that hippocampal IGF-1 protein concentrations during adolescence are highly regulated by circulating IGF-1, which were reduced by GH deficiency and restored by systematic GH replacement. In contrast, IGF-1 levels in the CSF were decreased by GH deficiency but not restored by GH replacement. Furthermore, analysis of gene expression using microarrays and RT-PCR indicated that circulating IGF-1 levels did not modify the transcription of IGF-1 or its receptor in the hippocampus but did regulate genes that are involved in microvascular structure and function, brain development, and synaptic plasticity, which potentially support brain structures involved in cognitive function during this important developmental period. GH-deficient dwarf (dw/dw) and heterozygous (HZ) rats were identified at postnatal day 33-34. Starting from d35, dw/dw rats received subcutaneous injection of either 300µg GH (dw/dw+GH) or saline (dw/dw+sal) for 7d or 30d. HZ animals received saline for the same periods as controls. Animals (n=4/group for each time point) were sacrificed, the hippocampi were dissected, and total RNA were isolated for subsequent transcriptomic profiling.

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Exome sequencing of short SGA children with IGF I and insulin resistance

Project description:Exome sequencing of short SGA children with IGF-I and insulin resistance. Collaboration with Professor David Dunger, University of Cambridge. Funded by NIHR.

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Regulation of germline proteostasis by insulin/IGF-1 signaling

Project description:Regulation of germline proteostasis by insulin/IGF-1 signaling

| PRJNA1078387 | ENA