Similar Datasets
Project description:The activity of early-life gene regulatory elements is hijacked in aging through pervasive AP-1–linked chromatin opening
| PRJNA924763 | ENA
Project description:Activation of T cells is dependent on the organized and timely opening and closing of chromatin. Herein, we identify AP-1 as the transcription factor that directs most of this remodeling. Chromatin accessibility profiling showed quick opening of closed chromatin in naive T cells within 5 h of activation. These newly opened regions were strongly enriched for the AP-1 motif, and indeed, ChIP-seq demonstrated AP-1 binding at >70% of them. Broad inhibition of AP-1 activity prevented chromatin opening at AP-1 sites and reduced the expression of nearby genes. Similarly, induction of anergy in the absence of co-stimulation during activation was associated with reduced induction of AP-1 and a failure of proper chromatin remodeling. The translational relevance of these findings was highlighted by the substantial overlap of AP-1-dependent elements with risk loci for multiple immune diseases, including multiple sclerosis, inflammatory bowel disease, and allergic disease. Our findings define AP-1 as the key link between T cell activation and chromatin remodeling.
| S-EPMC7037242 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2019-10-16 | GSE116698 | GEO
Project description:Education in people's early lives are positively related to their cognitive function, but its modulating effects on detailed cognition domains, its interaction with leisure activities and the associated brain changes have yet to be investigated. This report used data from 659 cognitively normal community dwelling elderly who completed neuropsychological tests, leisure activities measurement, and 78 of them underwent structural and diffusion MRI scans. We found that: (i) the highly educated elderly had a better cognitive functioning in multi-domains, higher frequencies of participation in knowledge-related leisure activities, and slower age-related reductions of executive function; (ii) the intellectual and social types of leisure activities mediated the association between education and multiple cognitive domains, including memory, language, attention and executive function; (iii) there was a significant age by education interaction on the gray matter volume of the anterior brain regions and white matter integrity; and (iv) the interaction between age and education affected cognition indirectly through white matter integrity analyzed using structural equation model. Overall, our results revealed that high education in early life served as a protective factor in aging that may help to postpone cognitive and brain reserve decline in cognitively normal aging.
| S-EPMC6682517 | biostudies-literature
Project description:ObjectivesNegative perceptions of aging can be self-fulfilling prophecies, predicting worse cognitive and physical outcomes. Although older adults are portrayed as either lonely curmudgeons or perfect grandparents, little research addresses how perceptions of aging relate to social outcomes. We considered whether more positive expectations about aging encourage older adults to maintain or bolster their social network connections and support.MethodThis study examined baseline, 12-, and 24-month questionnaire data from the Baltimore Experience Corps Trial, a longitudinal randomized volunteer intervention for adults aged 60 years and older. The associations between expectations regarding aging and different types of social support were tested using negative binomial and multiple regression models controlling for relevant covariates such as baseline levels of perceived support availability.ResultsParticipants with more positive expectations at baseline made more new friends 2 years later and had greater overall perceived support availability 12 months later. Notably, only participants with at least average perceived support availability at baseline showed an association between expectations and later support availability.DiscussionThese results are the first to link overall expectations regarding aging to the social domain and suggest that the influence of perceptions of aging is not limited to physical or cognitive function.
| S-EPMC5926985 | biostudies-literature
Project description:Activation of T cells is dependent on organized and timely opening and closing of chromatin. We perform ATAC-seq (subseries 1), ChIP-seq (subseries 2), and RNA-seq (subseries 3) at 5, 24, and 60 h of T cell activation with anti-CD3 and -CD28 antibodies in human primary naïve CD4 T cells. We report that chromatin opening at early time points is established by AP-1 transcription factor and associated with transcriptional enhancer identified as risk loci for multiple immune diseases in human naïve CD4 T cells.
2019-10-16 | GSE116697 | GEO
Project description:Activation of T cells is dependent on organized and timely opening and closing of chromatin. We perform ATAC-seq (subseries 1), ChIP-seq (subseries 2), and RNA-seq (subseries 3) at 5, 24, and 60 h of T cell activation with anti-CD3 and -CD28 antibodies in human primary naïve CD4 T cells. We report that chromatin opening at early time points is established by AP-1 transcription factor and associated with transcriptional enhancer identified as risk loci for multiple immune diseases in human naïve CD4 T cells.
2019-10-16 | GSE116696 | GEO
Project description:Activation of T cells is dependent on organized and timely opening and closing of chromatin. We perform ATAC-seq (subseries 1), ChIP-seq (subseries 2), and RNA-seq (subseries 3) at 5, 24, and 60 h of T cell activation with anti-CD3 and -CD28 antibodies in human primary naïve CD4 T cells. We report that chromatin opening at early time points is established by AP-1 transcription factor and associated with transcriptional enhancer identified as risk loci for multiple immune diseases in human naïve CD4 T cells.
2019-10-16 | GSE116695 | GEO
Project description:ObjectiveTo test the hypothesis that cognitive activity across the life span is related to late-life cognitive decline not linked to common neuropathologic disorders.MethodsOn enrollment, older participants in a longitudinal clinical-pathologic cohort study rated late-life (i.e., current) and early-life participation in cognitively stimulating activities. After a mean of 5.8 years of annual cognitive function testing, 294 individuals had died and undergone neuropathologic examination. Chronic gross infarcts, chronic microscopic infarcts, and neocortical Lewy bodies were identified, and measures of β-amyloid burden and tau-positive tangle density in multiple brain regions were derived.ResultsIn a mixed-effects model adjusted for age at death, sex, education, gross and microscopic infarction, neocortical Lewy bodies, amyloid burden, and tangle density, more frequent late-life cognitive activity (estimate = 0.028, standard error [SE] = 0.008, p < 0.001) and early-life cognitive activity (estimate = 0.034, SE = 0.013, p = 0.008) were each associated with slower cognitive decline. The 2 measures together accounted for 14% of the residual variability in cognitive decline not related to neuropathologic burden. The early-life-activity association was attributable to cognitive activity in childhood (estimate = 0.027, SE = 0.012, p = 0.026) and middle age (estimate = 0.029, SE = 0.013, p = 0.025) but not young adulthood (estimate = -0.020, SE = 0.014, p = 0.163).ConclusionsMore frequent cognitive activity across the life span has an association with slower late-life cognitive decline that is independent of common neuropathologic conditions, consistent with the cognitive reserve hypothesis.
| S-EPMC3772831 | biostudies-literature
Project description:BackgroundImbalances in the gut microbial community (dysbiosis) of vertebrates have been associated with several gastrointestinal and autoimmune diseases. However, it is unclear which taxa are associated with gut dysbiosis, and if particular gut regions or specific time periods during ontogeny are more susceptible. We also know very little of this process in non-model organisms, despite an increasing realization of the general importance of gut microbiota for health.MethodsHere, we examine the changes that occur in the microbiome during dysbiosis in different parts of the gastrointestinal tract in a long-lived bird with high juvenile mortality, the ostrich (Struthio camelus). We evaluated the 16S rRNA gene composition of the ileum, cecum, and colon of 68 individuals that died of suspected enterocolitis during the first 3 months of life (diseased individuals), and of 50 healthy individuals that were euthanized as age-matched controls. We combined these data with longitudinal environmental and fecal sampling to identify potential sources of pathogenic bacteria and to unravel at which stage of development dysbiosis-associated bacteria emerge.ResultsDiseased individuals had drastically lower microbial alpha diversity and differed substantially in their microbial beta diversity from control individuals in all three regions of the gastrointestinal tract. The clear relationship between low diversity and disease was consistent across all ages in the ileum, but decreased with age in the cecum and colon. Several taxa were associated with mortality (Enterobacteriaceae, Peptostreptococcaceae, Porphyromonadaceae, Clostridium), while others were associated with health (Lachnospiraceae, Ruminococcaceae, Erysipelotrichaceae, Turicibacter, Roseburia). Environmental samples showed no evidence of dysbiosis-associated bacteria being present in either the food, water, or soil substrate. Instead, the repeated fecal sampling showed that pathobionts were already present shortly after hatching and proliferated in individuals with low microbial diversity, resulting in high mortality several weeks later.ConclusionsIdentifying the origins of pathobionts in neonates and the factors that subsequently influence the establishment of diverse gut microbiota may be key to understanding dysbiosis and host development. Video Abstract.
| S-EPMC7552511 | biostudies-literature