Gene Expression Differences in Prostate Cancers between Young and Old Men.
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ABSTRACT:
SUBMITTER: Ding Y
PROVIDER: S-EPMC5189936 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundCaloric restriction (CR) is considered to increase lifespan and to prevent various age-related diseases in different nonhuman organisms. Only a limited number of CR studies have been performed on humans, and results put CR as a beneficial tool to decrease risk factors in several age-related diseases. The question remains at what age CR should be implemented to be most effective with respect to healthy aging. The aim of our study was to elucidate the role of age in the transcriptional response to a completely controlled 30 % CR diet on immune cells, as immune response is affected during aging. Ten healthy young men, aged 20-28, and nine healthy old men, aged 64-85, were subjected to a 2-week weight maintenance diet, followed by 3 weeks of 30 % CR. Before and after 30 % CR, the whole genome gene expression in peripheral blood mononuclear cells (PBMCs) was assessed.ResultsExpression of 554 genes showed a different response between young and old men upon CR. Gene set enrichment analysis revealed a downregulation of gene sets involved in the immune response in young but not in old men. At baseline, immune response-related genes were higher expressed in old compared to young men. Upstream regulator analyses revealed that most potential regulators were controlling the immune response.ConclusionsBased on the gene expression data, we theorise that a short period of CR is not effective in old men regarding immune-related pathways while it is effective in young men.Trial registrationClinicalTrials.gov, NCT00561145.
| S-EPMC4968441 | biostudies-literature
Project description:Caloric restriction (CR) is considered to increase lifespan and to prevent various age-related diseases in different non-human organisms. Only a limited number of CR studies have been performed in humans, and results put CR as a beneficial tool to decrease risk factors in several age-related diseases. The question remains at what age CR should be implemented to be most effective with respect to healthy aging. The aim of our study was to elucidate the role of age in the transcriptional response to a 30% CR diet in immune cells, as immune response is affected during aging. Ten healthy young men, aged 20-34, and nine healthy old men, aged 64-85, were subjected to a two week weight maintenance diet, followed by three weeks of 30% CR. Before and after 30% CR, peripheral blood mononuclear cells’ (PBMCs) whole genome gene expression was assessed. Expression of 554 genes showed a different response between young and old men upon CR. Gene set enrichment analysis revealed a downregulation of gene sets involved in immune response in young men, but not in old men. At baseline, immune response-related genes were already higher expressed in old compared to young men. Upstream regulator analyses revealed that most potential regulators were controlling immune response, and were inhibited in young men upon CR, and activated in old men at baseline. Based on the gene expression data, we conclude that a short period of CR is more effective in young men compared to old men regarding immune related pathways.
2016-10-24 | GSE63117 | GEO
Project description:Caloric restriction (CR) is considered to increase lifespan and to prevent various age-related diseases in different non-human organisms. Only a limited number of CR studies have been performed in humans, and results put CR as a beneficial tool to decrease risk factors in several age-related diseases. The question remains at what age CR should be implemented to be most effective with respect to healthy aging. The aim of our study was to elucidate the role of age in the transcriptional response to a 30% CR diet in immune cells, as immune response is affected during aging. Ten healthy young men, aged 20-34, and nine healthy old men, aged 64-85, were subjected to a two week weight maintenance diet, followed by three weeks of 30% CR. Before and after 30% CR, peripheral blood mononuclear cellsâ (PBMCs) whole genome gene expression was assessed. Expression of 554 genes showed a different response between young and old men upon CR. Gene set enrichment analysis revealed a downregulation of gene sets involved in immune response in young men, but not in old men. At baseline, immune response-related genes were already higher expressed in old compared to young men. Upstream regulator analyses revealed that most potential regulators were controlling immune response, and were inhibited in young men upon CR, and activated in old men at baseline. Based on the gene expression data, we conclude that a short period of CR is more effective in young men compared to old men regarding immune related pathways. Gene expression was profiled in peripheral blood mononuclear cells (PBMCs) from young and old men before and after 30% caloric restriction.
2016-10-24 | E-GEOD-63117 | biostudies-arrayexpress
Project description:Purpose: We used RNA-seq to compare daily rhythms of gene expression in livers of young and old mice. Methods: Livers of young and old mice were processed for RNA-seq at 4-h interval across 2 days. Gene expression level was analyzed by hisat2 and StringTie. Results: We obtained ~10 million high quality sequencing reads per time point per sample after quality control and alignment. Gene expression levels of ~19,000 transcripts were obtained for both age groups. We found genome-wide differenes in gene expression level as well as rhythms in gene expression. Conclusions: Our study revealed genomwide differences in the level and rhythm of liver gene expression between young and old mice.
2019-12-31 | GSE113745 | GEO
Project description:Human neurons function over an entire lifetime, yet the molecular mechanisms which perform their functions and protecting against neurodegenerative disease during aging are still elusive. Here, we conducted a systematic study on the human brain aging by using the weighted gene correlation network analysis (WGCNA) method to identify meaningful modules or representative biomarkers for human brain aging. Significantly, 19 distinct gene modules were detected based on the dataset GSE53890; among them, six modules related to the feature of brain aging were highly preserved in diverse independent datasets. Interestingly, network feature analysis confirmed that the blue modules demonstrated a remarkably correlation with human brain aging progress. Besides, the top hub genes including PPP3CB, CAMSAP1, ACTR3B, and GNG3 were identified and characterized by high connectivity, module membership, or gene significance in the blue module. Furthermore, these genes were validated in mice of different ages. Mechanically, the potential regulators of blue module were investigated. These findings highlight an important role of the blue module and its affiliated genes in the control of normal brain aging, which may lead to potential therapeutic interventions for brain aging by targeting the hub genes.
| S-EPMC6119720 | biostudies-literature
Project description:AimSeveral genomic signatures are available to predict Prostate Cancer (CaP) outcomes based on gene expression in prostate tissue. However, no signature was tailored to predict aggressive CaP in younger men. We attempted to develop a gene signature to predict the development of metastatic CaP in young men.MethodsWe measured genome-wide gene expression for 119 tumor and matched benign tissues from prostatectomies of men diagnosed at ≤ 50 years and > 70 years and identified age-related differentially expressed genes (DEGs) for tissue type and Gleason score. Age-related DEGs were selected using the improved Prediction Analysis of Microarray method (iPAM) to construct and validate a classifier to predict metastasis using gene expression data from 1,232 prostatectomies. Accuracy in predicting early metastasis was quantified by the area under the curve (AUC) of receiver operating characteristic (ROC), and abundance of immune cells in the tissue microenvironment was estimated using gene expression data.ResultsThirty-six age-related DEGs were selected for the iPAM classifier. The AUC of five-year survival ROC for the iPAM classifier was 0.87 (95%CI: 0.78-0.94) in young (≤ 55 years), 0.82 (95%CI: 0.76-0.88) in middle-aged (56-70 years), and 0.69 (95%CI: 0.55-0.69) in old (> 70 years) patients. Metastasis-associated immune responses in the tumor microenvironment were more pronounced in young and middle-aged patients than in old ones, potentially explaining the difference in accuracy of prediction among the groups.ConclusionWe developed a genomic classifier with high precision to predict early metastasis for younger CaP patients and identified age-related differences in immune response to metastasis development.
| S-EPMC8081383 | biostudies-literature
Project description:BACKGROUND:Emergency Department (ED) are challenged by the increasing number of visits made by the heterogeneous population of elderly persons. This study aims to 1) compare chief complaints (triage categories) and level of priority; 2) to investigate their association with hospitalization after an ED visit; 3) to explore factors explaining the difference in hospitalization rates among community-dwelling older adults aged 65-84 vs 85+ years. METHODS:All ED visits of patients age 65 and over that occurred between 2005 and 2010 to the University of Lausanne Medical Center were analyzed. Associations of hospitalization with triage categories and level of priority using regressions were compared between the two age groups. Blinder-Oaxaca decomposition was performed to explore how much age-related differences in prevalence of priority level and triage categories contributed to predicted difference in hospitalization rates across the two age groups. RESULTS:Among 39'178 ED visits, 8'812 (22.5%) occurred in 85+ patients. This group had fewer high priority and more low priority conditions than the younger group. Older patients were more frequently triaged in "Trauma" (20.9 vs 15.0%) and "Home care impossible" (10.1% vs 4.2%) categories, and were more frequently hospitalized after their ED visit (69.1% vs 58.5%). Differences in prevalence of triage categories between the two age groups explained a quarter (26%) of the total age-related difference in hospitalization rates, whereas priority level did not play a role. CONCLUSIONS:Prevalence of priority level and in triage categories differed across the two age groups but only triage categories contributed moderately to explaining the age-related difference in hospitalization rates after the ED visit. Indeed, most of this difference remained unexplained, suggesting that age itself, besides other unmeasured factors, may play a role in explaining the higher hospitalization rate in patients aged 85+ years.
| S-EPMC6003168 | biostudies-literature
Project description:Aging of the peripheral nervous system (PNS) is associated with structural and functional changes that lead to a reduction in regenerative capacity and the development of age-related peripheral neuropathy. Myelin is a central component in maintaining physiological peripheral nerve function, and differences in myelin maintenance, degradation, formation and clearance have been suggested to contribute to age-related PNS changes. In addition, recent proteomic studies have elucidated the complex composition of the total myelin proteome in health and its changes in neuropathy models. However, changes in the myelin proteome of peripheral nerves during ageing have not been investigated. Hence, the aim of this proteomics experiment was to define proteome changes in isolated myelin fractions during ageing, by investigating myelin proteome profiles from young (nerves from 2-3 month old mice) and old (nerves from 18 months old mice) nerves.
2023-10-19 | PXD040719 | Pride
Project description:The incidence and mortality rates of prostate cancer are significantly higher in African-American men when compared to European-American men. We tested the hypothesis that differences in tumor biology contribute to this survival health disparity. Using microarray technology, we obtained gene expression profiles of primary prostate tumors resected from 33 African-American and 36 European-American patients. These tumors were matched on clinical parameters. We also evaluated 18 non-tumor prostate tissues from 7 African-American and 11 European-American patients. The resulting datasets were analyzed for expression differences on the gene and pathway level comparing African-American with European-American patients. Our analysis revealed a significant number of genes, e.g., 162 transcripts at a false-discovery rate less than 5%, to be differently expressed between African-American and European-American patients. Using a disease association analysis, we identified a common relationship of these transcripts with autoimmunity and inflammation. These findings were corroborated on the pathway level with numerous differently expressed genes clustering in immune response, stress response, cytokine signaling, and chemotaxis pathways. Furthermore, a two-gene tumor signature was identified that accurately differentiated between African-American and European-American patients. This finding was confirmed in a blinded analysis of a second sample set. In conclusion, the gene expression profiles of prostate tumors indicate prominent differences in tumor immunobiology between African-American and European-American men. The profiles portray the existence of a distinct tumor microenvironment in these two patient groups. Keywords: Microdissected tissue analysis
2008-01-01 | GSE6956 | GEO
Project description:About 15% of colorectal cancers harbor microsatellite instability (MSI). MSI-associated gene expression changes have been identified in colorectal cancers, but little overlap exists between signatures hindering an assessment of overall consistency. Little is known about the causes and downstream effects of differential gene expression.DNA microarray data on 89 MSI and 140 microsatellite-stable (MSS) colorectal cancers from this study and 58 MSI and 77 MSS cases from three published reports were randomly divided into test and training sets. MSI-associated gene expression changes were assessed for cross-study consistency using training samples and validated as MSI classifier using test samples. Differences in biological pathways were identified by functional category analysis. Causation of differential gene expression was investigated by comparison to DNA copy-number data.MSI-associated gene expression changes in colorectal cancers were found to be highly consistent across multiple studies of primary tumors and cancer cell lines from patients of different ethnicities (P < 0.001). Clustering based on consistent changes separated additional test cases by MSI status, and classification of individual samples predicted MSI status with a sensitivity of 96% and specificity of 85%. Genes associated with immune response were up-regulated in MSI cancers, whereas genes associated with cell-cell adhesion, ion binding, and regulation of metabolism were down-regulated. Differential gene expression was shown to reflect systematic differences in DNA copy-number aberrations between MSI and MSS tumors (P < 0.001).Our results show cross-study consistency of MSI-associated gene expression changes in colorectal cancers. DNA copy-number alterations partly cause the differences in gene expression between MSI and MSS cancers.
| S-EPMC2605660 | biostudies-literature