Similar Datasets
Project description:Sex modulates microglia in the aging brain
| PRJNA758568 | ENA
Project description:DNA methylation plays crucial roles during fetal development as well as aging. Whether the aging of the brain is programmed at the fetal stage remains untested. To test this hypothesis, mouse epigenetic clock (epiclock) was profiled in fetal (gestation day 15), postnatal (day 5), and aging (week 70) brain of male and female C57BL/6J inbred mice. Data analysis showed that on week 70, the female brain was epigenetically younger than the male brain. Predictive modeling by neural network identified specific methylations in the brain at the developing stages that were predictive of epigenetic state of the brain during aging. Transcriptomic analysis showed coordinated changes in the expression of epiclock genes in the fetal brain relative to the placenta. Whole-genome bisulfite sequencing identified sites that were methylated both in the placenta and fetal brain in a sex-specific manner. Epiclock genes and genes associated with specific signaling pathways, primarily the gonadotropin-releasing hormone receptor (GnRHR) pathway, were associated with the sex-bias methylations in the placenta as well as the fetal brain. Transcriptional crosstalk among the epiclock and GnRHR pathway genes was evident in the placenta that was maintained in the brain during development as well as aging. Collectively, these findings suggest that sex differences in the aging of the brain are of fetal origin and epigenetically linked to the placenta.
2022-08-22 | GSE157553 | GEO
Project description:We found that the microbiota influenced critical characteristics linked with aging.
2022-01-23 | GSE182719 | GEO
Project description:Fetal origin of sex-bias brain aging
| PRJNA661735 | ENA
Project description:Microglia, the brain’s resident macrophages, maintain brain homeostasis and respond to injury and infection. During aging they undergo functional changes, but the underlying mechanisms and their contributions to neuroprotection versus neurodegeneration are unclear. Previous studies suggested that microglia are sex dimorphic, so we compared microglial aging in mice of both sexes. RNA-sequencing of hippocampal microglia revealed more aging-associated changes in female microglia than male microglia, and more sex differences in old microglia than young microglia. Pathway analyses and subsequent validation assays revealed a stronger AKT-mTOR-HIF1α-driven shift to glycolysis among old female microglia and indicated that C3a production and detection was elevated in old microglia, especially in females. Recombinant C3a induced AKT-mTOR-HIF1α signaling and increased the glycolytic and phagocytic activity of young microglia. Single cell analyses attributed the aging-associated sex dimorphism to more abundant disease-associated microglia (DAM) in old female mice than old male mice, and evaluation of an Alzheimer’s Disease mouse model revealed that the metabolic and complement changes are also apparent in the context of neurodegenerative disease and are strongest in the neuroprotective DAM2 subset. Collectively, our data implicate autocrine C3a-C3aR signaling in metabolic reprogramming of microglia to neuroprotective DAM during aging, especially in females, and also in Alzheimer’s Disease.
2024-06-05 | GSE267529 | GEO
Project description:Fetal origin of sex-bias brain aging [RNA-seq]
| PRJNA888983 | ENA
Project description:An in-depth understanding of the molecular processes composing aging is crucial to develop therapeutic approaches that decrease aging as a key risk factor for cognitive decline. Herein, we present a spatio-temporal brain atlas (15 different regions) of microRNA expression across the mouse lifespan (7 time points) and two aging interventions. MicroRNAs are promising therapeutic targets, as they silence genes by complementary base-pair binding of messenger RNAs and mediate aging speed. We first established sex- and brain-region-specific microRNA expression patterns in young adult samples. Then we focused on sex-dependent and independent brain-region-specific microRNA expression changes during aging. We identified three sex-independent brain aging microRNAs (miR-146a-5p, miR-155-5p and miR-5100). For miR-155-5p, we showed that these expression changes are driven by aging microglia and target mTOR signaling pathway components and other cellular communication pathways. In this work, we identify strong sex-brain-region-specific aging microRNAs and microglial miR-155-5p as a promising therapeutic target.
2025-04-13 | GSE282207 | GEO
Project description:Heart failure and other cardiomyopathies have distinct presentations in males versus females that are often overlooked, leading to ineffective treatment, and contributing to the growing mortality from heart diseases. Understanding the differences in the pathogenesis of heart disease in males and females can guide early diagnostics and sex-specific therapy. Thus, there is a pressing need to investigate the sex-specificity of promoter and enhancer activity in the pathogenesis of heart failure. Here, using cap analysis of gene expression we characterize the sex-specific activity of transcriptional regulatory elements in 17 male and 14 female healthy and failing hearts. We show that differentially expressed transcribed regulatory elements between two sexes are spread throughout the entire genome in healthy and failing atria and ventricles, and are related to immune system, metabolic, cardiomyocyte function, and developmental pathways. Moreover, we found 720 genes with sex-dependent promoter switching of which 40 switched dominant promoters. Among those was CREM, a transcription factor, with a short repressive dominant isoform exclusive for males. CREM is related to extensive β-adrenergic receptor stimulation that leads to elevated arrhythmic activity, hypertrophy and heart dysfunction. Furthermore, we identified metabolic pathways being more responsible for female aging and developmental pathways for male aging. We also showed sex-specific aging patterns, such as age-specific promoter usage of 1,100 genes that behaved differently depending on sex, including UCKL1 and HAND2 linked to uridine metabolism and cardiac development, respectively.
2023-04-27 | GSE212695 | GEO
Project description:Microglia undergo sex-dimorphic transcriptional and metabolic rewiring during aging
| PRJNA1111779 | ENA
Project description:Dynamic remodeling in architecture and function of mammalian brain, especially in primate, rely on a precisely orchestrated molecular and cellular regulation at distinct levels. Here, we applied comprehensive RNA-seq and CAGE-Seq analysis to characterize dynamics of lncRNA expression in Rhesus macaque brain across postnatal development and aging. We identified 18 anatomically diverse lncRNA modules and 14 mRNA modules representing spatial, age and sex specificities respectively. Highly spatiotemporal- and sex-specific dynamic changes in lncRNA but mRNA expression and the negative correlation between lncRNAs and mRNAs, functionally associate with brain development and aging, especially in the neocortex. Together with in situ hybridization (ISH) and quantitative real time-PCR (qRT-PCR) data, our findings provide an initial insight into spatial-, age- and sex-related dynamics of lncRNA expression during postnatal brain development and aging in macaque, implying that high dynamics of lncRNA expression might represent a previously unappreciated regulatory system in shaping brain architecture and function.
2017-07-06 | GSE87176 | GEO