Project description:Molecular mechanisms of ovarian aging and female age-related fertility decline remain unclear. We surveyed the single-cell transcriptomic landscape of ovaries from young and aged non-human primates (NHPs) and identified seven ovarian cell types with distinct gene expression signatures, including oocyte and six types of ovarian somatic cells. In-depth dissection of gene expression dynamics of oocytes revealed four subtypes at sequential and stepwise developmental stages. Further analysis of cell type-specific aging-associated transcriptional changes uncovered the disturbance of antioxidant signaling specific to early-stage oocytes and granulosa cells, indicative of oxidative damage as a crucial factor in ovarian functional decline with age. Additionally, inactivated antioxidative pathways, increased reactive oxygen species and apoptosis were observed in granulosa cells from aged women. This study provides comprehensive understanding of the cell type-specific mechanisms underlying primate ovarian aging at single-cell resolution, revealing new diagnostic biomarkers and potential therapeutic targets for age-related human ovarian disorders.
Project description:In this study, we generated single-cell RNA sequencing (scRNA-seq) data from epithelial cells in the intestine, focusing on six distinct subsections during aging: the proximal small intestine, intermediate small intestine, distal small intestine, cecum, proximal colon and distal colon regions. Using a hashtag-labeled method, we aimed to create a comprehensive atlas of cellular changes during aging within these regions. Our objective is to uncover the underlying mechanisms of aging, leveraging the intestine as a model due to its highly proliferative nature. This dataset will provide valuable insights into the cellular dynamics of aging and contribute to the broader understanding of age-related processes.
Project description:The ovary is the first organ to age in the human body, affecting both fertility and overall health. However, the biological mechanisms underlying human ovarian aging remain poorly understood. Here we present a comprehensive single-nuclei multi-omics atlas of four young (ages 23–29 years) and four reproductively aged (ages 49–54 years) human ovaries. Our analyses reveal coordinated changes in transcriptomes and chromatin accessibilities across cell types in the ovary during aging, notably mTOR signaling being a prominent ovary-specific aging pathway. Cell-type-specific regulatory networks reveal enhanced activity of the transcription factor CEBPD across cell types in the aged ovary. Integration of our multi-omics data with genetic variants associated with age at natural menopause demonstrates a global impact of functional variants on gene regulatory networks across ovarian cell types. We nominate functional non-coding regulatory variants, their target genes and ovarian cell types and regulatory mechanisms. This atlas provides a valuable resource for understanding the cellular, molecular and genetic basis of human ovarian aging.
Project description:Aging is accompanied by the functional decline of all tissues, but it is still largely unknown how aging impacts different tissues in a cell type-specific manner. Here, we present the Aging Fly Cell Atlas (AFCA) that includes single-nucleus transcriptomes of the entire Drosophila head and body from both males and females at four different ages. We characterize 162 distinct cell types and present an in-depth analysis of cell type-specific aging features, including changes of cell composition, gene expression, number of expressed genes, transcriptome noise, and cell identity. By combining all aging features, including aging clock models predicting a cell’s age, we find cell-type specific aging patterns. Adipose tissues showed the highest aging score, followed by two cell types from the reproductive system. This transcriptomic atlas provides a valuable resource for the community to study fundamental principles of aging in complex organisms.