Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA327211 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:We discovered that WSTF is downregulated in senescent cells by autophagy degradation. Forced expression of WSTF inhibits senescence-associated secretory phenotype, via inhibition of chromatin accesibility over inflammatory genes.
2022-10-05 | GSE214409 | GEO
Project description:We discovered that WSTF is downregulated in senescent cells by autophagy degradation. Forced expression of WSTF inhibits senescence-associated secretory phenotype, via inhibition of chromatin accesibility over inflammatory genes.
2022-10-05 | GSE214408 | GEO
Project description:In arthritis, synovial fibroblast (SF) senescence is linked to the activation of a pro-inflammatory phenotype contributing to chronic arthritis pathogenesis. Additionally, senescent cells accumulate in ageing tissues further promoting ageing and inflammation. These cells have dysregulated mitochondrial function and metabolism, limited tissue regeneration, produce reactive oxygen species (ROS) and secrete bioactive molecules, including pro-inflammatory cytokines, chemokines and matrix-remodelling enzymes known as SASP (senescence-associated secretory phenotype). In vitro, senescent cells can induce a senescent phenotype in surrounding bystander cells. Interestingly, extracellular vesicles (EVs) have critical roles in cellular senescence and ageing and are mediators in intercellular communication. We hypothesize that senescent cells in osteoarthritic SFs induce senescence and/or a proinflammatory phenotype in non-senescent osteoarthritic SFs, mediated through EV cargo.
2022-10-15 | PXD032757 | Pride
Project description:ADAM19 Mediates Cellular Senescence and the Senescence-Associated Secretory Phenotype
2020-04-03 | MSV000085224 | MassIVE
Project description:Microglia are essential to maintain brain homeostasis, but when dysregulated, exert pathogenic functions in Alzheimer’s disease (AD). Recent evidence has implicated senescent/dystrophic microglia in the pathological process of AD. Whether microglial senescence is a cause or consequence of AD pathogenesis however is unclear. Here we report that autophagy, a lysosomal degradation pathway, restricts cellular senescence of microglia and confer neuroprotection in AD mouse model. Autophagy-deficient microglia show hallmarks of cellular senescence evidenced by reduced proliferation, increased Cdkn1a/p21Cip, dystrophy, and typical secretory phenotype. While disease-associated microglia (DAM) surrounding amyloid plaques exhibit heightened autophagy, autophagy deficient, senescent microglia (SAM) disengage from and thus fail to limit the diffusive amyloid plaques, causing enhanced tau phosphorylation and neurotoxicity in AD model. Treatment of senolytic drugs removes senescent microglia and alleviates neuropathology. Our study demonstrates a causal role of autophagy impairment in microglial senescence and neurotoxicity and suggests therapeutic potential of senolytic treatment for AD.
2023-04-24 | GSE192964 | GEO
Project description:Glucocorticoids, powerful anti-inflammatory and immunosuppressive agents, can decrease bone mass and quality and increase bone marrow adiposity. Here, we show that a small number of bone marrow adipocytes (BMAds) in mice undergo rapid cellular senescence in response to glucocorticoid treatment. The senescent BMAds acquire a senescence-associated secretory phenotype (SASP), which reinforces and spreads senescence in the bone/bone marrow microenvironment in a paracrine manner. Mechanistically, glucocorticoid treatment increases the synthesis of oxylipins such as 15d-PGJ2 in BMAds to positively regulate the activity of PPARγ, which stimulates the expression of key cellular senescence effector genes. PPARγ activation, in turn, promotes oxylipin synthesis in BMAds, forming a positive feedback loop. Inhibition of the initial BMAd senescence by deleting p16INK4a from adipocytes or pharmacological suppression of the SASP efficiently interrupts the secondary spread of senescent cells and alleviates glucocorticoid-induced bone deficits. We identify senescent BMAds as initial mediators for glucocorticoid-induced bone deterioration and reveal a lipid metabolism circuit that robustly triggers the senescence of BMAds.
2023-06-09 | GSE205732 | GEO
Project description:<p>Cellular senescence affects many physiological and pathological processes and is characterized by durable cell cycle arrest, an inflammatory secretory phenotype and metabolic reprogramming. Here, by using dynamic transcriptome and metabolome profiling in human fibroblasts with different subtypes of senescence, we show that a homeostatic switch which results in glycerol-3-phosphate (G3P) and phosphoethanolamine (PEtn) accumulation links lipid metabolism to the senescence gene expression program. Mechanistically, p53-dependent glycerol kinase (GK) activation and post-translational inactivation of Phosphate Cytidylyltransferase 2-Ethanolamine (PCYT2) regulate this metabolic switch, which promotes triglyceride accumulation in lipid droplets and induces the senescence gene expression program. Conversely, G3P phosphatase (G3PP) and Ethanolamine-Phosphate Phospho-Lyase (ETNPPL)-based scavenging of G3P and PEtn acts in a senomorphic way by reducing G3P and PEtn accumulation. Collectively, our study ties G3P and PEtn accumulation to controlling lipid droplet biogenesis and phospholipid flux in senescent cells, providing a potential therapeutic avenue for targeting senescence and related pathophysiology.</p>
2024-01-09 | MTBLS7118 | MetaboLights
Project description:Ultraviolet light is the dominant environmental oxidative skin stressor and a major skin aging factor. We studied which oxidized phospholipid (OxPL) mediators Ultraviolet A (UVA) would generate in primary human keratinocytes (KC). Mass spectrometric analysis of the oxidized phospholipidome of KC immediately or 24h post stress revealed dynamic changes in abundance of 174 oxidized phosphocholine species. Exposure to UVA and to in vitro UVA - oxidized phospholipids both activated, on transcriptome and proteome level, NRF2/antioxidant response signaling and lipid metabolizing enzyme expression, whereas UVA additionally initiated the unfolded protein response (UPR). We identified Nupr1 as an upstream transcriptional regulator of UVA/OxPL mediated gene expression that is itself transcriptionally regulated by reactive lipids, which also aggregate and crosslink recombinant Nupr1 protein. Nupr1 governs the basal and stress regulated expression of cell cycle, redox reactive, autophagy- and lipid metabolizing genes in epidermal keratinocytes, making it a potential key factor in skin ROS responses, -aging and -pathology.
2019-05-27 | PXD008050 | Pride
Project description:Iron accumulation drives fibrosis, senescence, and the senescence-associated secretory phenotype
| PRJEB62753 | ENA
Project description:Cellular senescence due to telomere dysfunction has been hypothesized to play a role in age-associated diseases including idiopathic pulmonary fibrosis (IPF). It has been postulated that paracrine mediators originating from senescent alveolar epithelia signal to surrounding mesenchymal cells and contribute to disease pathogenesis. However, murine models of telomere-induced alveolar epithelial senescence fail to display the canonical senescence-associated secretory phenotype (SASP) that is observed in senescent human cells. In an effort to understand human-specific responses to telomere dysfunction, we modelled telomere dysfunction-induced senescence in a human alveolar epithelial cell line. We hypothesized that this system would enable us to probe for differences in transcriptional and proteomic senescence pathways in vitro and to identify novel secreted protein (secretome) changes that potentially contribute to the pathogenesis of IPF. Following induction of telomere dysfunction, a robust senescence phenotype was observed. RNA-Seq analysis of the senescent cells revealed the SASP and comparisons to previous murine data highlighted species-specific responses to telomere dysfunction. We then conducted a proteomic analysis of the senescent cells using a novel biotin ligase capable of labeling secreted proteins. Candidate biomarkers selected from our transcriptional and secretome data were then evaluated in IPF and control patient plasma. Four novel proteins were found to be differentially expressed between the patient groups: stanniocalcin-1, contactin-1, tenascin C, and total inhibin. Our data show that human telomere-induced, alveolar epithelial senescence results in a transcriptional SASP that is distinct from that seen in analogous murine cells. Our findings suggest that studies in animal models should be carefully validated given the species-specific responses to telomere dysfunction. We also describe a pragmatic approach for the study of the consequences of telomere-induced alveolar epithelial cell senescence in humans.
2021-04-04 | PXD023381 | Pride