Project description:The mammalian brain is complex, with multiple cell types performing a variety of diverse functions, but exactly how each cell type is affected in aging remains largely unknown. Here we performed a single-cell transcriptomic analysis of young and old mouse brains. We provide comprehensive datasets of aging-related genes, pathways and ligand–receptor interactions in nearly all brain cell types. Our analysis identified gene signatures that vary in a coordinated manner across cell types and gene sets that are regulated in a cell-type specific manner, even at times in opposite directions. These data reveal that aging, rather than inducing a universal program, drives a distinct transcriptional course in each cell population, and they highlight key molecular processes, including ribosome biogenesis, underlying brain aging. Overall, these large-scale datasets provide a resource for the neuroscience community that will facilitate additional discoveries directed towards understanding and modifying the aging process.
Project description:The mammalian brain can be divided into distinct structural and functional regions to perform a variety of diverse functions, but during normal aging, exactly how each region is affected, and the information interaction changes between different regions, remains largely unknown. To gain a better insight into these processes, here we generate a single-cell spatial transcriptomic (ST) atlas of young and old mice brains involving cerebrum, brain stem and fiber tracts regions. Based on the unbiased classification of spatial molecular atlas, 27 distinguished brain spatial domains were obtained, which are similar to known anatomical regions, but slightly different. Through differential expression analysis and gene set enrichment analysis (GSEA), we identified aging-related genes and pathways that vary in a coordinated or opposite manner across regions. Combined with single-cell transcriptomic data, we characterized the spatial distribution of cell types, identified an up-regulated gene Ifi27 across regions and cell types in VIS region. Through ligand-receptor interaction analysis, we identified all possible information interaction changes between regions with aging. In summary, we establish a brain spatial molecular atlas (accessible online at https:) to provide a rich resource of spatially differentially expressed genes and information interaction, which may help to understand aging and provide novel insights into the molecular mechanism of brain aging.
Project description:Aging is the primary risk factor for most neurodegenerative diseases, yet the cell-type-specific progression of brain aging remains poorly understood. Here, human cell-type-specific transcriptomic aging clocks are developed using high-quality single-nucleus RNA sequencing data from post mortem human prefrontal cortex tissue of 31 donors aged 18–94 years, encompassing 73,941 high-quality nuclei. Distinct transcriptomic changes are observed across major cell types, including upregulation of inflammatory response genes in microglia from older samples. Aging clocks trained on each major cell type accurately predict chronological age, capture biologically relevant pathways, and remain robust in independent single-nucleus RNA-sequencing datasets, underscoring their broad applicability. Notably, cell-type-specific age acceleration is identified in individuals with Alzheimer's disease and schizophrenia, suggesting altered aging trajectories in these conditions. These findings demonstrate the feasibility of cell-type-specific transcriptomic clocks to measure biological aging in the human brain and highlight potential mechanisms of selective vulnerability in neurodegenerative diseases.
Project description:Aging is a major risk factor for neurodegenerative diseases that impose tremendous burdens on people and societies today. To understand trajectories of neurological aging in a primate, we generated one of the most comprehensive brain transcriptional datasets to date in a unique population of naturalistic, behaviorally phenotyped rhesus macaques. In this experiment, we generated 71,863 single-nucleus RNA-seq transcriptomes from the dorsolateral prefrontal cortex of 24 adult females spanning all ages. We find that, of all tested cell classes, oligodendrocytes were the only cell type to significantly increase in proportion with age. We also identify hundreds of genes that change significantly with age in one or more cell types, providing a valuable window into cell-type-specific aging in the prefrontal cortex. Our findings lend insight into biological mechanisms underlying brain aging and indicate promising directions for improving neurological health.