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What is the process used to induce senescence in epidermal cells? 


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Inducing senescence in epidermal cells involves the activation of p14^ARF, which leads to apoptosis, cell-cycle arrest, and subsequent p53-dependent senescence . This process requires continued expression of p14^ARF to commit cells to senescence, indicating a dependency on a persistent signal . Senescent cells formed in the epidermis are retained for extended periods even after transgene silencing, suggesting a lack of efficient removal mechanisms . Interestingly, epidermal hyperplasia induction can prevent the appearance of senescent cells upon p14^ARF activation . Understanding the dynamics of senescence induction in epidermal cells is crucial due to its implications in aging, tumor suppression, and tissue function .

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Oxidative stress induced by hydrogen peroxide was used to induce senescence in retinal pigment epithelial cells in the study, inhibiting cell proliferation and increasing senescence-associated beta-galactosidase staining.
Oxidative stress leading to single-strand breaks and down-regulation of PARP1 induces senescence in epidermal cells, activating a p38MAPK-P16-RB cell cycle arrest pathway as an adaptive response.
Genetic and epigenetic factors induce senescence in epidermal cells through processes like replicative exhaustion, DNA damage, and metabolic dysfunction, leading to a senescent state in aged skin.
p14ARF induction in the epidermis triggers apoptosis, cell-cycle arrest, and subsequent p53-dependent senescence, activating p19ARF and p16Ink4a through a feed-forward loop, requiring persistent p14ARF expression for senescence commitment.
Senescence in epidermal cells was induced by transgenic p14ARF expression, leading to apoptosis, cell-cycle arrest, and subsequent p53-dependent senescence, revealing a feed-forward loop involving p19ARF and p16Ink4a.

Related Questions

What are the molecular mechanisms involved in the induction of senescence in epidermal cells?5 answersThe induction of senescence in epidermal cells involves a complex interplay of molecular mechanisms. One key activator of senescence is p14ARF, which leads to apoptosis, cell-cycle arrest, and subsequent p53-dependent senescence. Senescent cells exhibit a stable cell cycle arrest and a hypersecretory phenotype, contributing to tissue remodeling and regeneration, but chronic accumulation can disrupt tissue homeostasis and promote inflammation, potentially leading to age-related diseases like cancer. Additionally, the MM1/ΔNp63α axis plays a role in regulating proliferative senescence in keratinocytes, with UVB irradiation upregulating MM1 and downregulating ΔNp63α, HERC3, and c-Myc, contributing to cellular senescence and photoaging of the epidermis. These findings highlight the dynamic and multifaceted nature of senescence induction in epidermal cells.
How does inflammatory signalling contribute to senescence induction in cells?5 answersInflammatory signaling plays a crucial role in inducing senescence in cells by activating specific pathways. Pro-inflammatory cytokines like IL-1β, IL-13, MCP-2, MIP-3α, and SDF-1α have been identified to efficiently induce cellular senescence through the activation of the EGFR-Ras signaling pathway. Additionally, factors secreted by senescent cells, known as the senescence-associated secretory phenotype (SASP), promote chronic inflammation and induce senescence in normal cells, creating a vicious cycle of inflammation and senescence. In a model of posttraumatic osteoarthritis, IL-17 was found to induce senescence in fibroblasts, and senescent cells skewed naive T cells towards a pro-inflammatory Th17 response, highlighting the role of senescent cells in promoting inflammation. Targeting inflammatory pathways involved in senescence induction may offer novel strategies for preventing age-related diseases.
How to prepare senescence model cells?5 answersTo prepare senescence model cells, various methods can be employed based on different cell types. One approach involves inducing senescence in cells by reducing the content or activity of multipotential stem cell ATF6, leading to ATF6 deficiency mesenchymal stem cells, which serve as an aging cell model. Another method includes using oxidative stress with hydrogen peroxide to induce premature senescence in non-transformed hepatocyte cell lines, mimicking molecular and metabolic signatures of aged liver cells. Additionally, a protocol has been developed to induce replicative senescence in hepatocytes by culturing cells for an extended period, followed by using conditioned medium from these senescent cells to induce senescence in other cells rapidly. These diverse approaches provide valuable models for studying aging processes and age-related diseases.
What are the senescent cell feutures?4 answersSenescent cells have several features. They undergo irreversible growth arrest and display a prolonged DNA damage response. They also experience reprogramming of the epigenome and show changes in response to nutrient signaling and in auto- and mitophagy. Senescent cells secrete a wide array of bioactive molecules, including cytokines, growth factors, and matrix metalloproteinases, known as the senescence-associated secretory phenotype (SASP). These cells accumulate in various tissues during aging and contribute to reduced regenerative capacity, chronic inflammation, and metabolic decline. Pharmacologic interventions that target senescent cells, such as senolytics (which ablate senescent cells) or senostatics (which suppress the senescent phenotype), have the potential to alleviate age-associated degenerative diseases and disabilities.
What are the mechanisms by which DNA methylation causes senescence?5 answersDNA methylation plays a role in senescence through various mechanisms. In horticultural crops, such as pak choi, DNA methylation changes during storage can accelerate leaf senescence. In humans, differences in DNA methylation levels in genes encoding senescent proteins have been observed in proteins conserved in chordates, metazoans, and eukaryotes, suggesting a role in the development of senescence-associated pathways during evolution. In Arabidopsis leaves, dark-induced senescence leads to changes in DNA methylation, particularly in CHH methylation, while global DNA methylation remains stable. Downregulation of EZH2, a histone methyltransferase, promotes senescence by initiating a DNA damage response and inducing the expression of senescence-associated genes. Senescence is associated with global DNA hypomethylation and site-specific DNA hypo- and hypermethylation, which may affect gene expression and genome stability.
What are the hallmarks of cellular senescence?3 answersCellular senescence is characterized by a decline in physiological functions and is associated with aging and degenerative diseases. The hallmarks of cellular senescence include the expression of senescence-associated beta-galactosidase (SA-β-gal) enzyme, stable DNA damage response (DDR), and the accumulation of senescence-associated secretory phenotype (SASP) mediators and reactive oxygen species (ROS). Senescent cells play a role in tissue dysfunction and aging, and their accumulation is associated with a decline in tissue function and age-related diseases such as osteoporosis. Senotherapeutic strategies, such as the use of natural compounds like quercetin, naringenin, and apigenin, have shown promise in reducing SASP and preventing the accumulation of senescent cells. The identification and elimination of senescent cells have gained attention in aging research, and understanding the molecular regulators of senescence phenotypes is important for developing therapeutic targets.

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