Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA254323 | ENA |
REPOSITORIES: ENA
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Project description:Human ageing affects the immune system resulting in an overall decline in immunocompetence. Although all immune cells are affected during aging, the functional capacity of T cells is most influenced and is linked to decreased responsiveness to infections and impaired differentiation. We studied age-related changes in DNA methylation and gene expression in CD4+ and CD8+ T cells from younger and older individuals. We observed marked difference between T cell subsets, with increased number of methylation changes and higher methylome variation in CD8+ T cells with age. The majority of age-related hypermethylated sites were located at CpG islands of silent genes and enriched for repressive histone marks. Specifically, in CD8+ T cell subset we identified strong inverse correlation between methylation and expression levels in genes associated with T cell mediated immune response (LGALS1, IFNG, CCL5, GZMH, CCR7, CD27 and CD248) and differentiation (SATB1, TCF7, BCL11B and RUNX3). Our results thus suggest the link between age-related epigenetic changes and impaired T cell function.
2015-05-29 | GSE59065 | GEO
Project description:The impact of healthy aging on molecular programming of immune cells is poorly understood. Here, we report comprehensive characterization of healthy aging in human classical monocytes, with a focus on epigenomic, transcriptomic, and proteomic alterations, as well as the corresponding proteomic and metabolomic data for plasma, using healthy cohorts of 20 young and 20 older males (~27 and ~64 years old on average). For each individual, we performed eRRBS-based DNA methylation profiling, which allowed us to identify a set of age-associated differentially methylated regions (DMRs) – a novel, cell-type specific signature of aging in DNA methylome. Hypermethylation events were associated with H3K27me3 in the CpG islands near promoters of lowly-expressed genes, while hypomethylated DMRs were enriched in H3K4me1 marked regions and associated with age-related increase of expression of the corresponding genes, providing a link between DNA methylation and age-associated transcriptional changes in primary human cells.
2022-02-16 | PXD021821 | Pride
Project description:Age-related methylation changes are associated with altered transcriptional circuitry [Methyl-seq]
| PRJNA200562 | ENA
Project description:Age-related methylation changes are associated with altered transcriptional circuitry [RNA-seq]
| PRJNA200629 | ENA
Project description:Aging reshapes the cellular and molecular landscape of mammalian tissues. These changes can be progressive, preceding linearly with age, or occur as abrupt transitions of the course of lifespan. To investigate the age-dependent cellular and molecular shifts we profiled matched proteomes and transcriptomes from male and female murine spleens across eight time points, from stable adults through to late life. The spleen was chosen to integrate understanding of age-dependent changes associated with immune surveillance, inflammaging, and immune-related proteostasis. Male and female mice follow distinct aging trajectories particularly in protein–RNA correlation in late life that reflects both compositional shifts and failure of post-transcriptional buffering. To investigate whether these changes could be attributed to specific cell-types within the spleen, we developed Celestial, a framework that assigns bulk gene changes to specific cell-types. We find that age-related bulk molecular changes could be attributed in part to compositional remodeling of cell-types—expansion of Gzmk+ CD8+ T cells and C1q+ macrophages alongside naive T cell loss. These results demonstrate that cell-type-aware interpretation can inform bulk multi-omic data for accurate mechanistic inference in heterogeneous tissues.
2026-04-18 | PXD077337 | panorama
Project description:Aging of immune system is characterized by progressive decline of physiological and cellular function of T cells. Recent studies of naïve T cells from young and old mice have identified age-related altered gene expressions but the mechanisms underlying age associated changes of naïve T cells remain poorly understood. Here we compared the transcriptome and chromatin accessibility in mature CD4 and CD8 thymocytes and in naïve CD4 and CD8 T cells of spleen between young (6-8 weeks) and old (79-121 weeks) C57Bl/6 mice. We used Agilent microarray method and identified the age-related altering gene expressions 1) only in mature CD4 and CD8 T cell from thymus, 2) shared by both thymus and spleen naïve T cells, and 3) only in naïve T cells from spleen. The shared changes include increased chemokine and chemokine receptor expressions and decreased cell cycle regulator expression. We further analyzed the chromatin basis of altered gene expression using Assaying Transposase Accessible Chromatin with high-throughput sequencing (ATAC-seq) between young and old mice. We have identified age-related changes of chromatin accessibility in T cells from thymus and spleen, and some correlated changes between gene expression and chromatin accessibility. Overall, we observedmore age-related alterations of gene expression and chromatin accessibility inthymus than in spleen, suggesting some age-related changes of T cells in thymus did not retain in periphery. Together, our findings have identified tissue specific altered gene expressions and chromatin status in T cells during aging and further study of these altered genes will shed new insights into the mechanisms underlying these age-related changes.
2021-03-19 | GSE112390 | GEO
Project description:Aging of immune system is characterized by progressive decline of physiological and cellular function of T cells. Recent studies of naïve T cells from young and old mice have identified age-related altered gene expressions but the mechanisms underlying age associated changes of naïve T cells remain poorly understood. Here we compared the transcriptome and chromatin accessibility in mature CD4 and CD8 thymocytes and in naïve CD4 and CD8 T cells of spleen between young (6-8 weeks) and old (79-121 weeks) C57Bl/6 mice. We used Agilent microarray method and identified the age-related altering gene expressions 1) only in mature CD4 and CD8 T cell from thymus, 2) shared by both thymus and spleen naïve T cells, and 3) only in naïve T cells from spleen. The shared changes include increased chemokine and chemokine receptor expressions and decreased cell cycle regulator expression. We further analyzed the chromatin basis of altered gene expression using Assaying Transposase Accessible Chromatin with high-throughput sequencing (ATAC-seq) between young and old mice. We have identified age-related changes of chromatin accessibility in T cells from thymus and spleen, and some correlated changes between gene expression and chromatin accessibility. Overall, we observedmore age-related alterations of gene expression and chromatin accessibility inthymus than in spleen, suggesting some age-related changes of T cells in thymus did not retain in periphery. Together, our findings have identified tissue specific altered gene expressions and chromatin status in T cells during aging and further study of these altered genes will shed new insights into the mechanisms underlying these age-related changes.
2021-03-19 | GSE112391 | GEO
Project description:Epigenetic drift, the stochastic accumulation of DNA methylation changes over time, contributes to transcriptional variability in aging. To investigate this, whole blood samples from 24 beagles in three age groups (3, 5, and 10 years) were analyzed using whole-genome bisulfite sequencing (WGBS) and RNA sequencing (RNA-seq). DNA methylation was profiled at approximately 20 million CpG sites, and gene expression was quantified across 30 thousand genes to assess age-related epigenetic and transcriptional changes. Actively expressed genes exhibited lower methylation levels near transcription start sites compared to non-expressed genes across all dogs, highlighting the role of DNA methylation in gene regulation. We then observed an increased degree of DNA methylation drift and expression level variability in aged dogs, potentially indicating a disruption in stable regulatory patterns and molecular heterogeneity. Pairwise comparisons across age groups identified 2,320 age-associated differentially methylated regions (DMRs) encompassing 39,369 CpGs, which were significantly enriched in exon and promoter regions, suggesting their non-random distribution in the genome. Additionally, we identified age-associated DNA methylation and gene expression changes using unsupervised cluster analysis classified into three patterns: early-to-mid, mid-to-late, and progressive. Gene sets across all patterns were commonly overrepresented in the immune system, morphogenesis, and signal transduction pathways. Notably, mid-to-late transition clusters showed a strong association with cell cycle regulation and cellular senescence, suggesting that epigenetic modifications may contribute to dysregulated cell cycle control and reduced regenerative capacity. This study provides insights into nonlinear and linear aging trajectories by integrating epigenomic and transcriptomic features, revealing regulatory mechanisms of age-related molecular changes.
2025-12-31 | E-MTAB-15578 | biostudies-arrayexpress