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:Aging-related degeneration of pancreatic islet cells contributes to impaired glucose tolerance and diabetes. Endocrine cells age heterogeneously, complicating the effort to unravel the molecular drives underlying endocrine aging. To overcome these obstacles, we undertook single-cell RNA sequencing of pancreatic islet cells obtained from young and aged non-diabetic cynomolgus monkeys. Despite sex differences and increased single-cell level transcriptional variations, aged β-cells showed increased unfolded protein response (UPR) along with the accumulation of protein aggregates. We observed transcriptomic dysregulation of UPR components linked to canonical ATF6 and IRE1 signaling, comprising adaptive UPR during pancreatic aging. Notably, we found age-related β-cell-specific upregulation of HSP90B1, an ER-located chaperone, impeded high glucose-induced insulin secretion. Our work decodes aging-associated transcriptomic changes that underlie pancreatic islet functional decay at the single-cell resolution and indicates that targeting UPR components may prevent loss of proteostasis, suggesting an avenue for therapies to delay β-cell aging and prevent aging-related diabetes.
Project description:Ovarian aging is characterized by the progressive depletion of primordial follicle reserve, leading to irregular patterns of ovulation and menopause. The basic mechanisms that underlie the ovarian aging and follicle decline is unknown. We sought to explore the role of cellular senescence and epigenomic mechanisms in ovarian aging. Here, we present the transcriptomic changes observed in the ovaries with age using the age groups 3mo, 6mo, 9mo and 12mo (n=5 per group except for 12mo which has an n=4). The age groups capture timepoints from sexual maturation to reproductive health decline.
Project description:Aging is a multifactorial process with significant functional alterations of the human body including endocrinal systems which control the whole-body physiology and metabolism. In this vein, aging-induced decline of endocrine function are associated with multiple physiological and metabolic diseases. However, aging-associated molecular shifts in the pituitary gland, the central organ of the endocrine system, have not been dissected systemically. In this study, we conducted single-cell transcriptomic analysis of the anterior pituitary gland by comparing old and young male mice. Single-cell transcriptomics not only increased the resolution for clustering of various cell types in the pituitary gland, but also enabled detailed analysis of differential expression and intercellular communication caused by aging. In summary, our study constructed the first single-cell transcriptomic atlas of pituitary aging and identified associated features of in a single-cell level, providing resources to develop novel potential therapeutic targets for aging-associated endocrine dysfunction.
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.