Aging affects expression and variability of genes in the human liver
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE133815 | GEO | 2019/07/04
REPOSITORIES: GEO
Similar Datasets
Project description:Although increased vascular stiffness is more prominent in aging males than females, and males are more prone to vascular disease with aging, no study has investigated the genes potentially responsible for gender differences in vascular aging. We tested the hypothesis that the transcriptional adaptation to aging differs in males and females using a monkey model, which is not only physiologically and phylogenetically closer to humans than the more commonly studied rodent models, but also is not afflicted with the most common forms of vascular disease that accompany the aging process in humans, e.g., atherosclerosis, hypertension, and diabetes. Gene expressions of monkey aorta from four groups (YF, OF, YM, OM) were detected to find out the molecular mechanism of aorta stiffness. Experiment Overall Design: Four groups were used in this experiment. 6 samples per group.The transcriptional profile of the aorta was compared by high-density microarrays between young and old males or females. About 600 genes were expressed differentially when comparing old versus young animals. Analysis of the different groups was further performed by gene ontology.We also analyzed whether the transcriptional regulation described above might correspond to specific transcription factors
2008-06-15 | E-GEOD-6599 | biostudies-arrayexpress
Project description:Aging and sex have a strong influence on the functional capacity of the immune system. In general, the immune response in females is stronger than that in males, but there is little information about the effect of aging on this difference. To address this question, we performed a transcriptomic analysis of peripheral blood mononuclear cells derived from nonagenarians and young controls. We found 337 and 269 genes to be differentially expressed (p<0.05, fold change >1.5 or <-1.5) in nonagenarian females and males, respectively; 177 of these were changed in both sexes. An analysis of the affected signaling pathways revealed a clear sex bias: the number of significantly changed pathways was 43 in females and 40 in males; 23 were shared. These data show that the effects of aging on the immune system are significantly different in males and females. Our study population consisted of 146 nonagenarians (103 females, 43 males) and 30 young controls (19-30 years of age, 21 females, 9 males). In our study, we analyzed the gene expression difference between nonagenarian and control women as well as between nonagenarian and control males and then compared these results.
2013-01-10 | E-GEOD-40366 | biostudies-arrayexpress
Project description:Aging and sex have a strong influence on the functional capacity of the immune system. In general, the immune response in females is stronger than that in males, but there is little information about the effect of aging on this difference. To address this question, we performed a transcriptomic analysis of peripheral blood mononuclear cells derived from nonagenarians and young controls. We found 337 and 269 genes to be differentially expressed (p<0.05, fold change >1.5 or <-1.5) in nonagenarian females and males, respectively; 177 of these were changed in both sexes. An analysis of the affected signaling pathways revealed a clear sex bias: the number of significantly changed pathways was 43 in females and 40 in males; 23 were shared. These data show that the effects of aging on the immune system are significantly different in males and females. Our study population consisted of 146 nonagenarians (103 females, 43 males) and 30 young controls (19-30 years of age, 21 females, 9 males). In our study, we analyzed the gene expression difference between nonagenarian and control women as well as between nonagenarian and control males and then compared these results.
2015-01-22 | E-GEOD-65219 | biostudies-arrayexpress
Project description:The goals of this study are to compare genome-wide DNA methylation levels in young and aged oocytes,and to investigate the transgenerational inheritance of methylome profiles in oocytes during natural aging. We apply a novel protocol of rapamycin to overcome the DNA methylation drift associated with oocyte aging. 8-week-old female mice were injected intraperitoneally with rapamycin or vehicle for 40 weeks. At the end of the experiment, females (48 weeks, F0) were paired with young adult (~4 mo old) males to produce F1 offspring (OF1 and ORaF1). An F2 generation (OF2 and ORaF2) resulted from mating F1 female at 44~48 weeks of age with young adult males. To generate YF1 and YF2 as normal control (offspring of young mother), we mated females (~8 weeks) with young adult males. Then we collect oocytes (F0,F1 and F2 generations)，sperm ( F1 and F2 generations) and hippocampus (F1 female offspring) from different groups to investigate the transgenerational inheritance of DNA methylome profiles associated with oocyte aging by the single cell whole-genome methylation sequencing (sc-WGBS). We found that oocytes from aged mother exhibited increased DNA methylation levels in CpG sites. Maternal aging related methylome changes can be inherited transgenerationally though oocyte to the germ line of F1 and F2 offspring. The application of rapamycin during the course of oocyte aging could reverse these DNA methylation alterations, and it can ameliorate several neurobehavioral aging trails that were in observed in aged oocyte offspring. WGBS-seq on DNA from hippocampal tissue revealed a number of differentially methylated (P<0.05) genes in OF1 and ORaF1 compared with YF1, and some of the enriched pathways were associated with aging process, such as PI3K-Akt signaling pathway (akin to transcriptional alterations above), MAPK signaling and Ras signaling pathway .
2022-12-31 | GSE164139 | GEO
Project description:Aging and sex have a strong influence on the functional capacity of the immune system. In general, the immune response in females is stronger than that in males, but there is little information about the effect of aging on this difference. To address this question, we performed a transcriptomic analysis of peripheral blood mononuclear cells derived from nonagenarians and young controls. We found 337 and 269 genes to be differentially expressed (p<0.05, fold change >1.5 or <-1.5) in nonagenarian females and males, respectively; 177 of these were changed in both sexes. An analysis of the affected signaling pathways revealed a clear sex bias: the number of significantly changed pathways was 43 in females and 40 in males; 23 were shared. These data show that the effects of aging on the immune system are significantly different in males and females.
2015-01-22 | GSE65219 | GEO
Project description:We explored how aging impacts transcriptional dynamics using single-cell RNA-sequencing to profile hundreds of CD4+ T cells from young and old mice from two divergent species. In young animals, immunological challenge drives a conserved transcriptomic switch from highly variable to tightly regulated gene expression, characterized by a strong up-regulation of a core activation program, coupled with a decrease in cell-to-cell variability. Aging significantly perturbed the activation of this core program, and increased expression heterogeneity across the population of cells in both species.
2016-07-21 | E-MTAB-4888 | biostudies-arrayexpress
Project description:Microglia, the brain’s principal immune cells, have been implicated in the pathogenesis of Alzheimer’s disease (AD), a condition shown to affect more females than males. Although sex differences in microglial function and transcriptomic programming have been described across development and in disease models of AD, no studies have comprehensively identified the sex divergences that emerge in the aging mouse hippocampus. Further, existing models of AD generally develop pathology (amyloid plaques and tau tangles) early in life and fail to recapitulate the aged brain environment associated with late-onset AD. Here, we examined and compared the transcriptomic and translatomic sex effects in young and old murine hippocampal microglia. Hippocampal tissue from C57BL6/N and microglial NuTRAP mice of both sexes were collected at young (5-6 month-old [mo]) and old (22-25 mo) ages. Cell sorting and affinity purification techniques were used to isolate the microglial transcriptome and translatome for RNA-sequencing and differential expression analyses. Flow cytometry, qPCR, and imaging approaches were used to confirm the transcriptomic findings. There were marginal sex differences identified in the young hippocampal microglia, with most differentially expressed genes (DEGs) restricted to the sex chromosomes. Both sex chromosomally- and autosomally-encoded sex differences emerged with aging. These sex DEGs identified at old age were primarily female-biased and enriched in senescent and disease-associated microglial signatures. Pathway analyses identified upstream regulators induced to a greater extent in females than in males, including inflammatory mediators IFNG, TNF, and IL1B, as well as AD-risk genes TREM2 and APP. These data suggest that female microglia adopt disease-associated and senescent phenotypes in the aging mouse hippocampus, even in the absence of disease pathology, to a greater extent than males. This sexually divergent microglial phenotype may explain the difference in susceptibility and disease progression in the case of AD pathology. Future studies will need to explore sex differences in microglial heterogeneity in response to AD pathology and determine how sex-specific regulators (i.e., sex chromosomal or hormonal) elicit these sex effects.
2023-08-18 | GSE233400 | GEO
Project description:Gene expression profiles were assessed in the hippocampus (HC), entorhinal cortex (EC), superior frontal gyrus (SG), and postcentral gyrus (PCG) across the lifespan of 63 cognitively intact individuals from 20-99 years old. New perspectives on the global gene changes that are associated with brain aging emerged, revealing two overarching concepts. First, different regions of the forebrain exhibited substantially different gene profile changes with age. For example, comparing equally powered groups, 5,029 probe sets were significantly altered with age (20-59 vs. 60-99) in the superior frontal gyrus, compared with 1,110 in the entorhinal cortex. Prominent change occurred in the 6th-7th decades across cortical regions, suggesting that this period is a critical transition point in brain aging, particularly in males. Second, clear gender differences in brain aging were evident across the lifespan, suggesting that the brain undergoes sexually dimorphic changes in gene expression not only in development but also in later life. Globally across all brain regions, males showed more gene change than females. Further, Gene Ontology analysis revealed that different categories of genes were predominantly affected in males vs. females. Notably, the male brain was characterized by global decreased catabolic and anabolic capacity with aging, with downregulated genes heavily enriched in energy production and protein synthesis/transport categories. Increased immune activation was a prominent feature of aging in both sexes, with more widespread activation in the female brain. These data open new opportunities to explore age-dependent changes in gene expression that set the balance between neurodegeneration and compensatory mechanisms in the brain, and suggest that this balance is set differently in males and females, an intriguing and novel idea. HgU133plus2.0 microarray chips were used to profile gene expression in 4 brain regions of cognitively intact humans, across the adult lifespan (ages 20-99). Experiment Overall Design: Postmortem brain tissue was collected from ADRC brain banks. Cases were preferentially selected where 3 or more brain regions were available.
2008-10-26 | E-GEOD-11882 | biostudies-arrayexpress
Project description:Aging is a complex biological process associated with progressive loss of physiological function and susceptibility to several diseases, such as cancer and neurodegeneration. Exosomes are involved in many cellular signaling pathways, and their cargo may serve as promising disease or aging biomarkers. These membrane-bound extracellular vesicles facilitate the transport of intracellular contents to proximal and distal cells in the body. Here, we investigated two omics approaches for exosome analysis. To overcome the challenges of plasma exosome contamination with abundant soluble plasma proteins, we developed a high throughput method to isolate highly purified exosomes from human plasma by sequential size exclusion chromatography and ultrafiltration. First, we used data-dependent acquisitions from offline high-pH reversed-phase fractions of exosome lysate to generate a deep spectral library comprising ~2,300 exosome proteins. Second, in a pilot aging study, we used comprehensive data-independent acquisitions to compare plasma exosomes from young (20 to 26 yrs) and old (60 to 66 yrs) individuals. We quantified 1,318 exosome proteins, and levels of 144 proteins were significantly different in young and old plasma groups (Q<0.05 and >1.5-fold change). We also analyzed exosome miRNA cargo and detected 331 miRNAs. Levels of several were significantly different in young and old individuals. In addition, 88 and 17 miRNAs were unique to old and young individuals, respectively. Plasma exosome biomarkers have great potential for translational studies investigating biomarkers of aging and age-related diseases and to monitor therapeutic aging interventions.
2021-01-30 | MSV000086782 | MassIVE
Project description:This dataset of cognitively normal controls is a subset of the GSE48350 dataset, which additionally contains microarray data from AD brains. Gene expression profiles were assessed in the hippocampus (HC), entorhinal cortex (EC), superior frontal gyrus (SG), and postcentral gyrus (PCG) across the lifespan of 63 cognitively intact individuals from 20-99 years old. New perspectives on the global gene changes that are associated with brain aging emerged, revealing two overarching concepts. First, different regions of the forebrain exhibited substantially different gene profile changes with age. For example, comparing equally powered groups, 5,029 probe sets were significantly altered with age (20-59 vs. 60-99) in the superior frontal gyrus, compared with 1,110 in the entorhinal cortex. Prominent change occurred in the 6th-7th decades across cortical regions, suggesting that this period is a critical transition point in brain aging, particularly in males. Second, clear gender differences in brain aging were evident across the lifespan, suggesting that the brain undergoes sexually dimorphic changes in gene expression not only in development but also in later life. Globally across all brain regions, males showed more gene change than females. Further, Gene Ontology analysis revealed that different categories of genes were predominantly affected in males vs. females. Notably, the male brain was characterized by global decreased catabolic and anabolic capacity with aging, with downregulated genes heavily enriched in energy production and protein synthesis/transport categories. Increased immune activation was a prominent feature of aging in both sexes, with more widespread activation in the female brain. These data open new opportunities to explore age-dependent changes in gene expression that set the balance between neurodegeneration and compensatory mechanisms in the brain, and suggest that this balance is set differently in males and females, an intriguing and novel idea. Keywords: Normal gene expression patterns across the adult lifespan
2008-10-09 | GSE11882 | GEO