Old Human Serum Increases Apoptosis and Molecular Ageing Markers In Human Hippocampal Progenitor Cells
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ABSTRACT:
PROVIDER: PRJNA416774 | ENA |
REPOSITORIES: ENA
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Project description:The aim of this study was to compare the effects of old versus young serum on genome-wide expression in human hippocampal progenitor cells (HPC0A07/03C) as they differentiate into neurons/glial cells.
2017-11-02 | GSE106403 | GEO
Project description:Age-related alteration in neural stem cell function is linked to neurodegenerative conditions and cognitive decline. In rodents, this can be reversed by exposure to a young systemic milieu and conversely, the old milieu can inhibit stem cell function in young rodents. In this study, we investigated the in vitro effect of the human systemic milieu on human hippocampal progenitor cells (HPCs) using human serum from early adulthood, mid-life and older age. We showed that neuroblast number following serum treatment is predictive of larger dentate gyrus, CA3, CA4 and whole hippocampus volumes and that allogeneic human serum from asymptomatic older individuals induced a two-fold increase in apoptotic cell death of HPCs compared with serum from young adults. General linear models revealed that variability in markers of proliferation and differentiation was partly attributable to use of antihypertensive medication and very mild cognitive decline among older subjects. Finally, using an endophenotype approach and whole-genome expression arrays, we showed upregulation of established and novel ageing molecular hallmarks in response to old serum. Serum from older subjects induced a wide range of cellular and molecular phenotypes, likely reflecting a lifetime of environmental exposures. Our findings support a role for the systemic enviroment in neural stem cell maintenance and are in line with others highlighting a distinction between neurobiological and chronological ageing. Finally, the herein described serum assay can be used by future studies to further analyse the effect of environmental exposures as well as to determine the role of the systemic environment in health and disease.
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Project description:The ovary is the first organ to age in the human body, affecting both fertility and overall health in women1-8. However, the biological mechanisms underlying human ovarian ageing remain poorly understood. Here we performed single-cell multi-omics analysis of young and reproductively aged human ovaries to understand the molecular and cellular basis of ovarian ageing in humans. Our analysis reveals coordinated changes in transcriptomic output and chromatin accessibility across cell types during ageing, including elevated mTOR and MAPK signaling, decreased activity of the oxidative phosphorylation and DNA damage repair pathways, and an increased signature of cellular senescence. By constructing cell type-specific regulatory networks, we uncover enhanced activity of the transcription factor CEBPD across cell types in the aged ovary, with a corresponding significant loss of activity of most cell identity-associated transcription factors. Moreover, by performing integrative analyses of our single-nuclei multi-omics data with common genetic variants associated with age at natural menopause (ANM) from genome-wide association studies, we demonstrate a global impact of functional variants on changes in gene regulatory networks across ovarian cell types. Finally, we nominate about a dozen of functional non-coding variants, their target genes and cell types and regulatory mechanisms that underlie genetic association with ANM. This work provides a comprehensive multimodal landscape of human ovarian ageing and mechanistic insights into inherited variation of ANM.
2023-03-12 | GSE202601 | GEO
Project description:We aim to improve anti-ageing drug discovery, currently achieved through laborious and lengthy longevity analysis. Recent studies demonstrated that the most accurate molecular method to measure human age is based on CpG methylation profiles, as exemplified by several epigenetics clocks that can accurately predict an individual’s age. Here, we developed CellAge, a new epigenetic clock that measures subtle ageing changes in primary human cells in vitro. As such it provides a unique tool to measure effects of relatively short pharmacological treatments on ageing. We validated our CellAge clock against known longevity drugs such as rapamycin and trametinib. Moreover, we uncovered novel anti-ageing drugs, torin2 and Dactolisib (BEZ-235), demonstrating the value of our approach as a screening and discovery platform for anti-ageing strategies. CellAge outperforms other epigenetic clocks in measuring subtle ageing changes in primary human cells in culture. The tested drug treatments reduced senescence and other ageing markers, further consolidating our approach as a screening platform. Finally, we showed that the novel anti-ageing drugs we uncovered in vitro, indeed increased longevity in vivo. Our method expands the scope of CpG methylation profiling from measuring human chronological and biological age from human samples in years, to accurately and rapidly detecting anti-ageing potential of drugs using human cells in vitro, providing a novel accelerated discovery platform to test sought after geroprotectors.
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Project description:Human bone-marrow-derived mesenchymal stem cells from young and old donors and tenogenic, chondrogenic and osteogenic constructs derived from these were subject to RNASeq and miRNASeq. We wished to identify common pathways of musculoskeletal ageing.
2016-11-01 | E-MTAB-3427 | biostudies-arrayexpress
Project description:Human bone-marrow-derived mesenchymal stem cells from young and old donors and tenogenic, chondrogenic and osteogenic constructs derived from these were subject to RNASeq and miRNASeq. We wished to identify common pathways of musculoskeletal ageing.
2016-12-28 | E-MTAB-4879 | biostudies-arrayexpress