Human primary fetal lung fibroblasts (HFL-1) undergoing replicative senescence
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE144703 | GEO | 2020/08/10
REPOSITORIES: GEO
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Project description:Human primary fetal lung fibroblasts (HFL-1) undergoing replicative senescence
| PRJNA604609 | ENA
Project description:Telomere shortening in populations of human mammary epithelial cells (HMECs) that survive early replicative arrest (M0) by the inactivation of p16INK4A during cell culture on plastic dishes leads to a state of permanent replicative arrest termed senescence. While culture of HMECs on feeder layers abrogates M0 and p16INK4A inactivation, progressive telomere attrition in these cells also eventually results in permanent replicative arrest. Expression of telomerase prevents both senescence on plastic (S-P) and senescence on feeder layers (S-FL) in HMECs, as it does also in cultured primary human fibroblasts. We report here that the gene expression profiles of senescence in HMECs of the same lineage maintained under different culture conditions showed surprisingly little commonality. Moreover, neither of these senescence-associated profiles in HMECs resembles the profile for senescence in human fibroblasts. These results indicate that senescence-associated alterations in gene expression resulting from telomere attrition are affected by culture conditions as well as by cell origins, and argue that replicative senescence at the molecular level is a diverse rather than unique cellular process.
2005-11-01 | E-SMDB-2210 | biostudies-arrayexpress
Project description:Chronic lung diseases significantly impact the aging population globally, but their etiology is largely unknown, and the therapeutic options are minimal. Cellular senescence has been increasingly recognized as an essential driving mechanism for chronic lung diseases. Remodeling in subcellular compartments is commonly observed in senescent cells, which reciprocally regulates the senescent progression. Roles of peroxisomes in cellular senescence have been documented, but the molecular mechanisms for this regulation remain poorly understood. Here, we showed that the peroxisome pathway and the shuttling receptor PEX5 are downregulated during replicative and oxidative senescence in human fetal lung fibroblast 1 (HFL-1) cells. PEX5 knockdown can induce senescence via transcriptional suppression of LAMP1 and autophagic flux. Further study revealed that activation of the p38 MAPK signaling pathway and subsequent nuclear localization of transcription factor EB (TFEB) are the significant retrograde signals contributing to the PEX5 regulation of cellular senescence. Metabolomics analysis identified a substantial increase in taurine levels in cells with PEX5 overexpression. Reciprocally, treatment of cells with taurine enhanced PEX5 levels in the senescent HFL-1 cells and the lungs of aged mice and alleviated senescence, suggesting the presence of a taurine-dependent response in PEX5 regulation of cellular senescence. Collectively, our findings provided new insights into the peroxisomal regulation of cellular senescence by integrating the p38 MAPK retrograde signaling pathway and taurine metabolism, which may help develop anti-aging strategies to treat chronic lung diseases.
2024-04-16 | GSE263751 | GEO
Project description:By transcriptome analysis of IMR-90 human fibroblasts following oncogene-induced senescence (OIS) and replicative senescence (RS), we identified commonly regulated genes in both conditions.
2017-03-30 | GSE86546 | GEO
Project description:Sequencing of human HFF fibroblasts during replicative senescence (smallRNA)
| PRJNA483225 | ENA
Project description:Cellular replicative senescence, a state of permanent cell-cycle arrest that occurs following an extended period of cell division in culture, has been linked to organismal aging, tissue repair and tumorigenesis. In this study, we comparatively investigated the global lipid profiles and mRNA content of proliferating and senescent-state BJ fibroblast cells. We found that both the expression levels of lipid-regulating genes, as well as the abundance of specific lipid families, are actively regulated. We further found that 19 polyunsaturated triacylglycerol species showed the most prominent changes during replicative senescence. We argue that diversion of polyunsaturated fatty acids to glycerolipid biosynthesis could be responsible for the accumulation of specific triacylglycerols. This, in turn, could be one of the cellular mechanisms to prevent lipotoxicity under increased oxidative stress conditions observed during replicative senescence. Collectively, our results place regulation of specific lipid species to a central role during replicative senescence.
2017-03-31 | GSE94280 | GEO
Project description:<p><strong>BACKGROUND:</strong> Periodontal ligament mesenchymal stem cells (PDLSCs) are a promising cell resource for cell-based regenerative medicine in dentistry. PDLSCs inevitably acquire a senescent phenotype after prolonged in vitro expansion, and the key regulators of cells during replicative senescence remain unclear.</p><p><strong>METHODS:</strong> We cultured periodontal ligament stem cells to passages 4, 10 and 20 (P4, P10, P20). The senescent phenotypes, proliferation and migration ability of PDLSCs (P4, P10, P20) were detected, and non-targeted metabonomic sequencing was performed. We treated PDLSCs with AICAR and detected the expression of FOXO1, FOXO3a, FOXO6 and AMPK phosphorylation (p-AMPK) levels of replicating senescent PDLSCs to explore the correlation between the metabolic changes and the AMPK pathway.</p><p><strong>RESULTS:</strong> Immunofluorescence staining of γ-H2AX, β-galactosidase staining, cell scratch test and qPCR were performed to confirm the occurrence of replicative senescence in PDLSCs during passaging. Three groups of cells at passage 4 (P4), passage 10 (P10) and passage 20 (P20) were collected for non-targeted metabolomics analysis. Metabonomic sequencing showed that the metabolism of replicative senescence in PDLSCs varied significantly. In particular, the content of fatty acid metabolites decreased with senescence, including capric acid, stearic acid, myristic acid and dodecanoic acid. KEGG pathway analysis showed that the AMPK signaling pathway was closely related to AMP levels. The AMP:ATP ratio increased in senescent PDLSCs; however, the levels of p-AMPK and the profile of FOXO1 and FOXO3a, which are downstream of the AMPK signaling pathway, decreased with senescence. We treated PDLSCs with AICAR, an activator of the AMPK pathway, and the phosphorylated AMPK level at P20 PDLSCs was partially restored. </p><p><strong>CONCLUSION:</strong> In summary, our study suggests that the metabolic process of PDLSCs is active in the early stage of senescence, prefers to consume fatty acids, and is attenuated in the later stages of senescence. AMP accumulates in replicative senescent PDLSCs; however, the sensitivity of AMPK phosphorylation sites is impaired, causing senescent PDLSCs to fail to respond to changes in energy metabolism. Our findings provide a new basis for the clinical application of periodontal ligament stem cells.</p>
2022-11-15 | MTBLS4568 | MetaboLights
Project description:Telomere shortening in populations of human mammary epithelial cells (HMECs) that survive early replicative arrest (M0) by the inactivation of p16INK4A during cell culture on plastic dishes leads to a state of permanent replicative arrest termed senescence. While culture of HMECs on feeder layers abrogates M0 and p16INK4A inactivation, progressive telomere attrition in these cells also eventually results in permanent replicative arrest. Expression of telomerase prevents both senescence on plastic (S-P) and senescence on feeder layers (S-FL) in HMECs, as it does also in cultured primary human fibroblasts. We report here that the gene expression profiles of senescence in HMECs of the same lineage maintained under different culture conditions showed surprisingly little commonality. Moreover, neither of these senescence-associated profiles in HMECs resembles the profile for senescence in human fibroblasts. These results indicate that senescence-associated alterations in gene expression resulting from telomere attrition are affected by culture conditions as well as by cell origins, and argue that replicative senescence at the molecular level is a diverse rather than unique cellular process.
2005-11-01 | E-SMDB-2046 | biostudies-arrayexpress
Project description:Analysis of the senescence transcriptome in TRF2dBdM-induced senescence and replicative senescence [microarray]
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Project description:microRNA profiles of hADSC during replicative senescence
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