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GSE11845
Mus musculus
150 Downloadable Samples
Illumina mouseRef-8 v1.1 expression beadchip
Description
Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending lifespan
Publication Title
Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending life span.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 47 Downloadable Samples
Illumina HumanHT-12 V4.0 expression beadchip, Illumina humanRef-8 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Age-associated changes in basal NF-κB function in human CD4+ T lymphocytes via dysregulation of PI3 kinase.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples- Mus musculus
- 72 Downloadable Samples
- Illumina MouseRef-8 v2.0 expression beadchip
Description
Calorie restriction (CR) is the most robust non-genetic intervention to universally delay the onset of age-related diseases and extend mean and maximum lifespan. However, species, strain, sex, diet, age of onset, and level of CR are emerging as important variables to consider for a successful CR response. Here, we investigated the role of strain, sex and level of CR on outcomes of health and survival in mice. Response to CR varied from lifespan extension to no effect on survival, while consistently delaying the onset and impact of diseases independently of strain, sex and level of dietary restriction. CR led to transcriptional and metabolomics changes in the liver indicating anaplerotic filling of the Krebs cycle together with fatty acid fueling of mitochondria. Additionally, CR prevented the age-associated decline in the proteostasis network. Further, CR increased mitochondrial number and preserved their ultrastructure and function with age. Abrogation of mitochondrial function by deletion of fumarate hydratase or malate dehydrogenase 2 negated the life-prolonging effects of CR in yeast and worms. In F1 hybrid strains of mice, the lifespan response to CR tracked with the dam, indicating that the mitochondrial haplotype is an important regulator of CR. Our data illustrate the complexity of the CR responses within a single animal species in the context of aging, with a clear separation of outcomes related to health and survival, highlighting the complexities of translation of CR into human interventions.
Publication Title
Effects of Sex, Strain, and Energy Intake on Hallmarks of Aging in Mice.
Sample Metadata Fields
Sex, Specimen part
View Samples- Macaca mulatta, Mus musculus, Homo sapiens, Rattus norvegicus
- 46 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip, Illumina ratRef-12 v1.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Conserved and species-specific molecular denominators in mammalian skeletal muscle aging.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 58 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
Deregulation of the translational machinery is emerging as a critical contributor to lymphomagenesis. Various miRNA alterations have been identified in lymphoma, but their role in disrupting the cap-dependent translation regulation complex remains poorly understood. Here, we demonstrate the translation initiation factor, eIF4GII, as a direct target and major mediator of miR-520c-3p function through 3UTR of eIF4GII mRNA. We established that elevated miR-520c-3p represses translation, initiates premature senescence and blocks cell proliferation in diffuse large B-cell lymphoma (DLBCL). Moreover, miR-520c-3p overexpression diminishes DLBCL cells colony formation and reduces tumor growth in a lymphoma xenograft mouse model. miR-520c-3p overexpressing cells display lowered eIF4GII levels. Consequently, downregulation of eIF4GII by siRNA induces cellular senescence, decreases cell proliferation and ability to form colonies. Our in vitro and in vivo findings we further validated in patient samples; DLBCL primary cells demonstrated low miR-520c-3p levels with reciprocally highly up-regulated eIF4GII protein expression. In contrast, normal donor B-cell lymphocytes had low levels of eIF4GII protein and elevated miR-520c-3p levels. Our results provide evidence that the tumor suppressor effect of miR-520c-3p is mediated through repression of cap-dependent translation while inducing senescence and that eIF4GII is a key effector of this anti-tumor activity. These findings may have implications for therapeutic interventions in patients with DLBCL.
Publication Title
Down-regulation of eIF4GII by miR-520c-3p represses diffuse large B cell lymphoma development.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 45 Downloadable Samples
- Illumina humanRef-8 v2.0 expression beadchip
Description
Immune impairment and high circulating level of pro-inflammatory cytokines are landmarks of human aging. However, the molecular basis of immune dysregulation and the source of inflammatory markers remain unclear. Here we demonstrate that in the absence of overt cell stimulation, gene expression mediated by the transcription factor NF-B is higher in purified and rested human CD4+ T lymphocytes from older compared to younger individuals. This increase of NF-B -associated transcription includes transcripts for pro-inflammatory cytokines such as IL-1 and chemokines such as CCL2 and CXCL10. We demonstrate that NF-B up-regulation is cell-intrinsic and mediated in part by phosphatidylinositol 3-kinase (PI3K) activity induced in response to metabolic activity, which can be moderated by rapamycin treatment. Our observations provide direct evidence that dysregulated basal NF-B activity may contribute to the mild pro-inflammatory state of aging.
Publication Title
Age-associated changes in basal NF-κB function in human CD4+ T lymphocytes via dysregulation of PI3 kinase.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples- Mus musculus
- 44 Downloadable Samples
- Illumina MouseRef-8 v2.0 expression beadchip
Description
The mammalian RNA-binding protein AUF1 (AU-binding factor 1, also known as heterogeneous nuclear ribonucleoprotein D, hnRNP D) binds to numerous mRNAs and influences their post-transcriptional fate. Given that many AUF1 target mRNAs encode muscle-specific factors, we investigated the function of AUF1 in skeletal muscle differentiation. In mouse C2C12 myocytes, where AUF1 levels rise at the onset of myogenesis and remain elevated throughout myocyte differentiation into myotubes, RIP (RNP immunoprecipitation) analysis indicated that AUF1 binds prominently to Mef2c (myocyte enhancer factor 2c) mRNA, which encodes the key myogenic transcription factor Mef2c. By performing mRNA half-life measurements and polysome distribution analysis, we found that AUF1 associated with the 3UTR of Mef2c mRNA and promoted Mef2c translation without affecting Mef2c mRNA stability. In addition, AUF1 promoted Mef2c gene transcription via a lesser-known role of AUF1 in transcriptional regulation. Importantly, lowering AUF1 delayed myogenesis, while ectopically restoring Mef2c expression levels partially rescued the impairment of myogenesis seen after reducing AUF1 levels. We propose that Mef2c is a key effector of the myogenesis program promoted by AUF1.
Publication Title
RNA-binding protein AUF1 promotes myogenesis by regulating MEF2C expression levels.
Sample Metadata Fields
Sex, Specimen part, Cell line, Time
View Samples- Mus musculus
- 26 Downloadable Samples
- Illumina MouseRef-8 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Blast traumatic brain injury-induced cognitive deficits are attenuated by preinjury or postinjury treatment with the glucagon-like peptide-1 receptor agonist, exendin-4.
Sample Metadata Fields
Sex, Specimen part, Treatment, Time
View Samples- Homo sapiens, Rattus norvegicus
- 25 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip, Illumina Rat Ref-12 v1
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Calorie restriction in humans inhibits the PI3K/AKT pathway and induces a younger transcription profile.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 1 Downloadable Sample
- Illumina humanRef-8 v2.0 expression beadchip, Illumina HumanHT-12 V4.0 expression beadchip
Description
Immune impairment and high circulating level of pro-inflammatory cytokines are landmarks of human aging. However, the molecular basis of immune dysregulation and the source of inflammatory markers remain unclear. Here we demonstrate that in the absence of overt cell stimulation, gene expression mediated by the transcription factor NF-B is higher in purified and rested human CD4+ T lymphocytes from older compared to younger individuals. This increase of NF-B -associated transcription includes transcripts for pro-inflammatory cytokines such as IL-1 and chemokines such as CCL2 and CXCL10. We demonstrate that NF-B up-regulation is cell-intrinsic and mediated in part by phosphatidylinositol 3-kinase (PI3K) activity induced in response to metabolic activity, which can be moderated by rapamycin treatment. Our observations provide direct evidence that dysregulated basal NF-B activity may contribute to the mild pro-inflammatory state of aging.
Publication Title
Age-associated changes in basal NF-κB function in human CD4+ T lymphocytes via dysregulation of PI3 kinase.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples