Project description:Aging induces functional declines in the mammalian brain, increasing its vulnerability to cognitive impairments and neurodegenerative disorders. Among various interventions to slow aging and delay age-related diseases, caloric restriction (CR) consistently extends lifespan across species. However, the specific molecular and cellular mechanisms through which CR benefits the aging brain remain unclear. In this study, we performed spatiotemporal profiling of mouse brains to uncover detailed mechanisms underlying the anti-aging effects of CR. We analyzed the transcriptional states of over half million single cells from mouse brain samples across various ages and in response to CR treatment. Monitoring the dynamics of over 300 transcriptionally distinct cellular states, we captured the temporal dynamics of cellular states particularly vulnerable to aging and those rescued by CR (e.g., CR delays the expansion of inflammatory glia and preserves neurogenesis cells). Further spatial transcriptome analysis revealed gene expression and cellular dynamics across brain regions in aged mice upon CR treatment, uncovering region-specific anti-aging effects. In summary, our spatiotemporal mouse brain profiling delineated highly cell-type-specific molecular pathways in response to aging and CR, shedding light on the nuanced regulatory roles of CR across different cell types and brain regions.
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.
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.
Project description:Aged microglia contribute to maladaptive inflammation, but little is known about their progression from homeostasis to dysfunction during aging. Here, we analyze the spatiotemporal kinetics of microglial aging in the hippocampus. Spatially, the dynamics of age-related inflammatory changes in microglia vastly differ across adjoining regions. Using single cell RNA-Sequencing and in vitro approaches, we find that microglia aging proceeds progressively through functional intermediate states that are necessary for inflammatory activation.
Project description:Aged microglia contribute to maladaptive inflammation, but little is known about their progression from homeostasis to dysfunction during aging. Here, we analyze the spatiotemporal kinetics of microglial aging in the hippocampus. Spatially, the dynamics of age-related inflammatory changes in microglia vastly differ across adjoining regions. Using single cell RNA-Sequencing and in vitro approaches, we find that microglia aging proceeds progressively through functional intermediate states that are necessary for inflammatory activation.
Project description:Aged microglia contribute to maladaptive inflammation, but little is known about their progression from homeostasis to dysfunction during aging. Here, we analyze the spatiotemporal kinetics of microglial aging in the hippocampus. Spatially, the dynamics of age-related inflammatory changes in microglia vastly differ across adjoining regions. Using single cell RNA-Sequencing and in vitro approaches, we find that microglia aging proceeds progressively through functional intermediate states that are necessary for inflammatory activation.
Project description:Aged microglia contribute to maladaptive inflammation, but little is known about their progression from homeostasis to dysfunction during aging. Here, we analyze the spatiotemporal kinetics of microglial aging in the hippocampus. Spatially, the dynamics of age-related inflammatory changes in microglia vastly differ across adjoining regions. Using single cell RNA-Sequencing and in vitro approaches, we find that microglia aging proceeds progressively through functional intermediate states that are necessary for inflammatory activation.
Project description:This SuperSeries is composed of the following subset Series: GSE32050: 5-hydroxymethylcytosine-mediated epigenetic dynamics during neurodevelopment and aging [5hmC Capture and Seq] GSE32187: 5-hydroxymethylcytosine-mediated epigenetic dynamics during neurodevelopment and aging [mRNA profiling] Refer to individual Series
Project description:Inflammatory responses occur within the complex spatial context of tissues and organs, and many questions remain about how tissue structure and cellular communication shape their spatiotemporal dynamics. Here, we used single-cell RNA sequencing to screen for genes differentially expressed under LPS (lipopolysaccharide) and vehicle control conditions in epithelial cells in zebrafish larvae. We used this data to choose candidate genes for spatial gene expression analysis.