Ovarian senescence, transcriptomic, and epigenomic changes with aging
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ABSTRACT:
PROVIDER: PRJNA647687 | ENA |
REPOSITORIES: ENA
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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.
2020-07-23 | GSE154890 | GEO
Project description:In mammalian females, quiescent primordial follicles serve as the ovarian reserve and sustain normal ovarian function and egg production via folliculogenesis. The loss of primordial follicles causes ovarian aging. Cellular senescence, characterized by cell cycle arrest and production of the senescence-associated secretory phenotype (SASP), is associated with tissue aging. In the present study, we report that some quiescent primary oocytes in primordial follicles become senescent in adult mouse ovaries. The senescent primary oocytes share senescence markers characterized in senescent somatic cells. The senescent primary oocytes were observed in young adult mouse ovaries, remained at approximately 15% of the total primary oocytes during ovarian aging from 6 months to 12 months, and accumulated in aged ovaries. Administration of a senolytic drug ABT263 to 3-month-old mice reduced the percentage of senescent primary oocytes and the transcription of the SASP cytokines in the ovary. In addition, led to increased numbers of primordial and total follicles and a higher rate of oocyte maturation and female fertility. Our study provides experimental evidence that primary oocytes, a germline cell type that is arrested in meiosis, become senescent in adult mouse ovaries and that senescent cell clearance reduced primordial follicle loss and mitigated ovarian aging phenotypes.
2024-04-30 | GSE253194 | GEO
Project description:The understanding of how aging affects the cellular and molecular components of the human ovary and contributes to age-related fertility decline is still limited. Here, we systematically characterize human ovarian aging by combining single-cell RNA sequencing and spatial transcriptomics. We provide a comprehensive understanding of human ovarian aging and a resource for the development of new diagnostic biomarkers and therapeutic strategies.
2024-04-15 | GSE255690 | GEO
Project description:Depletion of oocytes and follicles and reduced oocyte quality contribute to age-associated ovarian senescence and infertility. Telomere shortening and altered methylation make two major contributions to general aging. Resveratrol acts as anti-oxidant and Sirt1 activator to alleviate aging including reproductive aging. It remains elusive whether resveratrol can reprogram the aging epigenome. We sought to examine aging ovarian epigenome and the potential effects of resveratrol by combined analysis of telomere length, transcriptome and methylome mainly in oocytes and also in granulosa cells, two major cell types in the ovary.
2021-09-26 | GSE184636 | GEO
Project description:Depletion of oocytes and follicles and reduced oocyte quality contribute to age-associated ovarian senescence and infertility. Telomere shortening and altered methylation make two major contributions to general aging. Resveratrol acts as anti-oxidant and Sirt1 activator to alleviate aging including reproductive aging. It remains elusive whether resveratrol can reprogram the aging epigenome. We sought to examine aging ovarian epigenome and the potential effects of resveratrol by combined analysis of telomere length, transcriptome and methylome mainly in oocytes and also in granulosa cells, two major cell types in the ovary.
2021-09-26 | GSE184635 | GEO
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.
2020-01-28 | GSE130664 | GEO
Project description:Epigenomic and transcriptomic analyses of epithelial ovarian cancer
| PRJNA495805 | ENA
Project description:Single-Cell Transcriptomic Atlas of Primate Ovarian Aging
| PRJNA540933 | ENA
Project description:Aging is a universal biological phenomenon linked to many diseases, such as cancer or neurodegeneration. However, the molecular mechanisms underlying aging, or how lifestyle interventions such as cognitive stimulation can ameliorate this process, are yet to be clarified. Here, we performed a multi-omic profiling, including RNA-seq, ATAC-seq, ChIP-seq, EM-seq, SWATH-MS and single cell Multiome scRNA and scATAC-seq, in the dorsal hippocampus of young and old mouse subjects which were subject to cognitive stimulation using the paradigm of environmental enrichment. In this study we were able to describe the epigenomic landscape of aging and cognitive stimulation.
2023-09-29 | PXD045567 | Pride
Project description:As a critical hallmark of senescent cells, the senescence-associated secretory phenotype (SASP) develops over the course of chronological aging and in diverse age-related conditions, and is a key driver of chronic inflammation and age-associated phenotypes. For years, the identification, characterization and pharmacological targeting of senescent cells have gained substantial attention in the field of aging and age-related pathologies. Pyruvate dehydrogenase kinase 4 (PDK4) is an important mitochondrial matrix enzyme in cellular energy regulation, and drives the metabolic reprogramming of mammalian cells towards a Warburg-like effect. Upregulation of PDK4 is responsible for enhanced production of lactate in the tissue microenvironment of aged organisms, potentially causing chronic inflammation and contributing to accelerated aging. Targeting PDK4 holds the potential to prevent lactate accumulation, minimize tissue damage and postpone senescence-associated systemic aging. Here we profiled the genome-wide expression of cells (mainly fibroblasts) in mouse pulmonary alveolus, with the assistance of laser capture microdissection (LCM) of primary lung tissues. Animals were allowed to naturally age, or subject to treatment by PDK4-IN (an anthraquinone derivative, PDK4 inhibitor). These data may provide a baseline to further determine the effects of lactate reduction by PDK4-specific targeting on cellular senescence, tissue homeostasis, and explore the wide implications of PDK4 expression in organismal aging and age-related morbidity.
2023-09-05 | GSE217808 | GEO