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Homo sapiens
6 Downloadable Samples
Illumina HiSeq 2500
Description
The accumulation of irreparable cellular damage restricts healthy lifespan after acute stress or natural aging. Senescent cells are thought to impair tissue function and their genetic clearance can successfully delay features of aging. Identifying how senescent cells avoid apoptosis would allow for the prospective design of anti-senescence compounds to address whether homeostasis can be restored. Here, we identify FOXO4 as a pivot in the maintenance of senescent cell viability. We designed a FOXO4-based peptide which selectively competes for interaction of FOXO4 with p53. In senescent cells, this results in p53 nuclear exclusion and cell-intrinsic apoptosis. Importantly, under conditions where it was well tolerated, the FOXO4 peptide restored liver function after Doxorubicin-induced chemotoxicity. Moreover, in fast aging XpdTTD/TTD, as well as in naturally aged mice the FOXO4 peptide could counteract the loss of fitness, fur density and renal function. Thus, it is possible to therapeutically target senescent cells and thereby effectively counteract senescence-associated loss of tissue homeostasis. Overall design: mRNA expression levels are compared between IR-induced senescent and proliferating IMR90 cells in triplicate
Publication Title
Targeted Apoptosis of Senescent Cells Restores Tissue Homeostasis in Response to Chemotoxicity and Aging.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Caenorhabditis elegans
- 8 Downloadable Samples
Affymetrix C. elegans Genome Array (celegans)
Description
We demonstrate that transcriptomic profiling of the NER mutant ercc-1 offers better understanding of the complex phenotypes of ercc-1 deficiency in C. elegans, as it does in mammalian models. There is a transcriptomic shift in ercc-1 mutants that suggests a stochastic impairment of growth and development, with a shift towards a higher proportion of males in the population. Extensive phenotypic analyses confirm that NER deficiency in C. elegans leads to severe developmental and growth defects and a reduced replicative lifespan, although post-mitotic lifespan is not affected. Results suggest that these defects are caused by an inability to cope with randomly occurring DNA damage, which may interfere with transcription and replication.
Publication Title
DNA damage leads to progressive replicative decline but extends the life span of long-lived mutant animals.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Illumina Genome Analyzer II
Description
In this study, we employed massively parallel sequencing technology to identify miRNAs expressed in B-cells from Ashkenazi Jewish centenarians, i.e., those living to a hundred and a human model of exceptional longevity, and younger controls without a family history of longevity. With data from 26.7 million reads comprising 9.4x108 bp from 3 centenarian and 3 control individuals, we discovered a total of 276 known miRNAs and 8 unknown miRNAs ranging several orders of magnitude in expression levels. A total of 22 miRNAs were found to be significantly upregulated, with only 2 miRNAs downregulated, in centenarians as compared to controls. Overall design: Examination of miRNA profile of two different ages
Publication Title
Comprehensive microRNA profiling in B-cells of human centenarians by massively parallel sequencing.
Sample Metadata Fields
Specimen part, Race, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 2000
Description
The underlying relation between Parkinson disease (PD) etiopathology and its major risk factor, aging, is largely unknown. The nature of the specific age-related mechanisms promoting PD onset is experimentally difficult to elucidate because aging is a highly complex process contributed by multiple factors. Recent evidence, however, established a strong and causative link between genome stability and aging. To investigate a possible nexus between DNA damage accumulation, aging, and PD we examined DNA repair pathways associated with aging in laboratory animal models and human cases. We demonstrate that dermal fibroblasts from PD patients display flawed nucleotide excision repair (NER) capacity and that NER-defective mice exhibit typical PD-like pathological alterations, including decreased dopaminergic innervation in the striatum, increased phospho-synuclein levels, and defects in mitochondrial respiration. NER mouse mutants are also more sensitive to the prototypical PD toxin MPTP and their transcriptomic landscape shares important similarities with that of PD patients. Overall, our results demonstrate that specific defects in DNA repair impact the dopaminergic system, are associated with human PD pathology, and might therefore constitute a novel risk factor for PD by affecting the aging process. Overall design: In total 8 samples were analyzed, 4 controls and 4 Ercc1 mutants.
Publication Title
Inefficient DNA Repair Is an Aging-Related Modifier of Parkinson's Disease.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
To normalize transcriptome data we combined total RNA isolated from 10^6 resting or activated B cells with 1 µl of 1/10 dilution of Ambion’s ERCC RNA Spike-in Mix (92 mRNA standards). mRNA was then isolated and processed following Illumina’s RNA-seq protocol v2.
Publication Title
Global regulation of promoter melting in naive lymphocytes.
Sample Metadata Fields
Specimen part, Cell line
View Samples
GSE34378- Mus musculus
- 90 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Lifelong murine gene expression profiles in relation to chronological and biological aging in multiple organs
Publication Title
Life spanning murine gene expression profiles in relation to chronological and pathological aging in multiple organs.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 3 Downloadable Samples
- Illumina HiSeq 2000
Description
In this study, we investigate the anti-aging response induced by dietary restriction (DR) on gene expression level. For this, we carried out Ribosomal RNA depleted Total RNA sequencing in 16 weeks old Ercc1?/- ad libidum (AL), DR and wt mice. Overall design: Total RNA was extracted from fresh liver samples from 16 weeks old Ercc1?/- AL, DR and wt mice. Ribosomal RNA was depleted from the extracts by using RiboMinus kit (Ambion) then sequenced according to the Illumina TruSeq v3 protocol on HiSeq2000 platform.
Publication Title
Restricted diet delays accelerated ageing and genomic stress in DNA-repair-deficient mice.
Sample Metadata Fields
Age, Specimen part, Subject
View Samples- Mus musculus
- 7 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Inducible co-stimulator (ICOS) interaction with its ligand (ICOSL) is involved in several T cell effector functions. While blockade of ICOS:ICOSL interaction in chronic graft versus host disease (GVHD) seems benefi cial, results for acute GVHD remain controversial. To further elucidate its role in acute GVHD, C57BL / 6 mice were lethally irradiated and reconstituted with allogeneic spleen cells in the absence or presence of ICOSL-blocking mAb. Mice reconstituted with allogeneic spleen cells experienced severe GVHD and died untreated within 6 9 days after transplantation. Mice treated with an anti-ICOSL mAb starting from day 3 after transplantation gained weight again and survived for at least additional 12 days, although the treatment was already stopped at day 11 after transplantation. In contrast, the anti-ICOSL treatment starting from day 0 did not prevent GVHD. The diff erence between therapeutic (day 3) and prophylactic (day 0) anti-ICOSL treatment was independent of CD25 + CD4 + regulatory T cells since their depletion did not abrogate the therapeutic eff ect of ICOSL blockade. Microarray analysis revealed IFN- and chemokine up-regulation in spleen cells of prophylactically treated mice, emphasizing kinetic dependence of acute GVHD modulation via blockade of ICOS:ICOSL interaction.
Publication Title
Only therapeutic ICOS:ICOSL blockade alleviates acute graft versus host disease.
Sample Metadata Fields
Sex, Specimen part
View Samples- Glycine max
- 2522 Downloadable Samples
- Affymetrix Soybean Genome Array (soybean)
Description
To identify soybean genes and QTLs associated with quantitative resistance to infection by the oomycete pathogen Phytophthora sojae, we conducted a very large-scale microarray experiment using 2522 Affymetrix GeneChips. The experiment involved assaying a total of 298 soybean recombinant inbred lines together with internal checks.
Publication Title
Infection and genotype remodel the entire soybean transcriptome.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 12 Downloadable Samples
- Affymetrix Rat Gene 1.1 ST Array (ragene11st)
Description
Rat small intestine precision cut slices were exposed for 6 hours to in vitro digested yellow (YOd) and white onion extracts (WOd) that was followed by transcriptomics analysis. The digestion was performed to mimic the digestion that in vivo takes place in the stomach and small intestine. The transcriptomics response of the rat small intestine precision cut slices was compared to that of human Caco-2 cells and the pig in-situ small intestinal segment perfusion. The microarray data for the human Caco-2 cells (GSE83893) and the pig in-situ small intestinal segment perfusion (GSE83908) have been submitted separately from the current data on rat intestine. The goal was to obtain more insight into to which extent mode of actions depend on the experimental model. A main outcome was that each of the three models pointed to the same mode of action: induction of oxidative stress and particularly the Keap1-Nrf2 pathway.
Publication Title
Effects of Digested Onion Extracts on Intestinal Gene Expression: An Interspecies Comparison Using Different Intestine Models.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples