• Critically short telomeres activate cellular senescence or apoptosis, as mediated from the tumor suppressor p53, however in the lack of this checkpoint response, telomere dysfunction engenders chromosomal cancer and aberrations. (woofahs.com)
  • This oncosuppression is accomplished by initiating a form of cell death such as apoptosis or necrosis or by inducing cellular senescence. (wikipedia.org)
  • Cellular senescence refers to an irreversible growth arrest that is triggered by various intrinsic and extrinsic stresses. (korea.ac.kr)
  • Many recent studies have demonstrated that cellular senescence plays a crucial role in the regression of tumors exposed to ionizing radiation (IR), but the underlying mechanism remains unknown. (korea.ac.kr)
  • Here we show that the activation of integrin β4 is essential for IR-induced cellular senescence. (korea.ac.kr)
  • Tumor suppressor genes can promote cellular senescence, a state in which cells stop dividing, preventing the replication of damaged DNA. (pharmiweb.com)
  • Cellular senescence is a multifaceted process that arrests the proliferation of cells that are at risk of neoplastic transformation. (nature.com)
  • There is now substantial evidence that cellular senescence is a barrier to malignant tumorigenesis in vivo . (nature.com)
  • There is also mounting evidence that cellular senescence contributes to ageing. (nature.com)
  • Proliferating cells can initiate an additional response by adopting a state of permanent cell-cycle arrest that is termed cellular senescence. (nature.com)
  • Understanding the causes and consequences of cellular senescence has provided novel insights into how cells react to stress, especially genotoxic stress, and how this cellular response can affect complex organismal processes such as the development of cancer and ageing. (nature.com)
  • Campisi, J. Cellular senescence as a tumor-suppressor mechanism. (nature.com)
  • Cellular senescence is one of the main mechanisms involved [ 5 , 6 ]. (hindawi.com)
  • Aging kidney and CKD share many common characteristic features with increased cellular senescence, a conserved program characterized by an irreversible cell cycle arrest with altered transcriptome and secretome. (frontiersin.org)
  • In this review, we discuss current understanding of the role and mechanism of cellular senescence in kidney fibrosis. (frontiersin.org)
  • Cellular senescence is characterized by an irreversible and permanent cell cycle arrest coupled with altered transcriptome and secretome. (frontiersin.org)
  • In this review, we summarize the evidence linking cellular senescence to the pathogenesis of CKD and discuss current understanding of the mechanism and regulators controlling senescence. (frontiersin.org)
  • Because age-related cellular senescence and type 2 diabetes (T2D) have been recognised as risk factors for CRC development, the recent finding that type 2 diabetic patients present an elevated circulating volume of senescent cells raises the question whether type 2 diabetes facilitates the process of CRC tumorigenesis by inducing premature cell senescence. (frontiersin.org)
  • In this review, we will discuss the mechanisms according to which T2D induces cellular senescence and the role of type 2 diabetes-induced cellular senescence in the pathogenesis and progression of colorectal cancer. (frontiersin.org)
  • More recently, cellular senescence has been considered as an additional cause of age-related tumorigenesis. (frontiersin.org)
  • Senescence is a stress-response cellular state characterised by proliferative arrest but active metabolism ( 7 ). (frontiersin.org)
  • However, cellular senescence is not exclusive to ageing. (frontiersin.org)
  • Age-related and metabolic diseases such as type 2 diabetes (T2D) represent a source of cellular stress due to their disruptive effect on normal physiological processes and, therefore, can induce premature senescence ( 10 ). (frontiersin.org)
  • Deciphering the purpose, causes, and consequences of cellular senescence will provide us with a better understanding of the role they may play in a wide variety of diseases and how we can use therapies to remove them to improve human health. (sens.org)
  • This term might be the most unfamiliar to you, so let's take a deeper dive into the causes and consequences of cellular senescence. (sens.org)
  • So far, it seems like cellular senescence is a great mechanism to have in our bodies, but as is the case with many cellular processes, too much of a good thing can become a bad thing. (sens.org)
  • Cellular senescence, which recently has gained broad attention, is thought to be an important player in the onset and development of diabetic nephropathy. (hindawi.com)
  • In this issue, we generally review the mechanisms of cellular senescence in diabetic nephropathy, which involve telomere attrition, DNA damage, epigenetic alterations, mitochondrial dysfunction, loss of Klotho, Wnt/ β -catenin signaling activation, persistent inflammation, and accumulation of uremic toxins. (hindawi.com)
  • Moreover, we highlight the potential therapeutic targets of cellular senescence in diabetic nephropathy and provide important clues for clinical strategies. (hindawi.com)
  • Recently, the emerging role of cellular senescence in DN has attracted a broad attention. (hindawi.com)
  • In the present review, we will focus on the role of cellular senescence and its related mechanisms in DN. (hindawi.com)
  • Furthermore, we will explore the potential therapeutic targets of cellular senescence and provide important clues for clinical strategies in the management of DN. (hindawi.com)
  • Cellular aging or cellular senescence is the critical factor for the process of aging. (hindawi.com)
  • Numerous cellular proteins detect DNA damage and induce senescence , a permanent change of state characterized by morphological and gene expression changes. (massgenomics.org)
  • The best and most direct approach to the phenomenon of cellular senescence is to periodically destroy these cells, reducing their numbers to the greatest extent possible. (fightaging.org)
  • Ceramides that comprise the cell membrane of vertebrates are attracting interest as signaling mediators in a variety of cellular events, including apoptosis and cell senescence. (nova.edu)
  • Several hallmarks of cellular senescence, such as cell cycle arrest, expression of cyclin-dependent kinase inhibitors, DNA damages, and senescence-associated secretory profile were evaluated. (aging-us.com)
  • Etoposide-induced senescence model may help investigate the initiation of cellular senescence in chondrocytes, and provide a useful model to develop therapeutic approaches to target senescence in OA. (aging-us.com)
  • Cellular senescence has been described as one of the major drivers of aging [ 6 ] and has been implicated in the pathogenesis of many age-related diseases [ 7 ]. (aging-us.com)
  • Recently, cellular senescence has emerged as a new target to treat OA [ 8 ]. (aging-us.com)
  • Because a specific marker for cellular senescence has yet to be identified, a combination of markers should be used to identify SnCs [ 14 ]. (aging-us.com)
  • Considering the role of cellular senescence in age-related diseases including OA, the therapeutic potential of senolytic (drugs that induced SnCs death) and senomorphic (drugs that modulate the SASP) compounds have been contemplated with growing interest [ 15 ]. (aging-us.com)
  • Senescence can be induced by DNA DAMAGE or other cellular stresses, such as OXIDATIVE STRESS. (bvsalud.org)
  • Cellular senescence during AGING or due to extended passages of normal cells in culture and that is triggered by the DNA damage-response to TELOMERE SHORTENING or by repeated exposure to stress signals. (bvsalud.org)
  • RSV inhibited the expression of senescence markers (p53, p16, and p19), inflammasome markers (NLRP3 and Cas1 p20), and nuclear translocation of NF- κ B, hence alleviating infarction area, fibrosis, and cell apoptosis. (hindawi.com)
  • Chronic exposure to IL-1β induces only partial expression of senescence markers and does not allow us to conclude on its ability to induce senescence in chondrocytes. (aging-us.com)
  • On the basis of our finding that, integrin α6β4 is specifically activated and acts primarily to induce premature senescence in irradiated cancer cells, we propose that this integrin may be a valuable target and biomarker for radiotherapy. (korea.ac.kr)
  • Since then, many research teams have become interested in determining the hallmarks of cell senescence, the factors that induce it, and the effect of senescence on other cells and the body as a whole. (sens.org)
  • This study used etoposide, to induce DNA damage-related senescence or chronic exposure to IL-1β to entail inflammation-related senescence in human OA chondrocytes. (aging-us.com)
  • We look for papers that provide insights into the causes and progression of melanoma, aiming to advance the field and find ways to prevent this type of skin cancer, with a focus on the process of metastasis and invasion, proliferation, senescence, apoptosis or gene regulation. (wiley.com)
  • Senescent cells elicit their fibrogenic actions primarily by secreting an assortment of inflammatory and profibrotic factors known as the senescence-associated secretory phenotype (SASP). (frontiersin.org)
  • These secreted factors are collectively referred to as the senescence-associated secretory phenotype or the SASP. (sens.org)
  • Furthermore, senescent cells, with the secretory features known as the senescence-associated secretory phenotype (SASP), could produce proinflammatory cytokines, such as tumor necrosis factor- α (TNF- α ), interleukin-6 (IL-6), and monocyte chemoattractant protein1 (MCP-1), to greatly affect the neighboring cells [ 17 , 18 ]. (hindawi.com)
  • The aged immune system is characterized by the senescence -associated secretory phenotype, resulting in the release of proinflammatory cytokines contributing to inflamm-aging. (karger.com)
  • SnCs exhibit irreversible growth arrest accompanied by increased expression of cyclin-dependent kinase inhibitors (CDKi) such as p16 INK4a , and p21 Cip1 , accumulation of DNA damages, and secretion of diverse bioactive molecules known as the senescence-associated secretory phenotype (SASP). (aging-us.com)
  • Although the conventional activities of p53 such as cell cycle arrest, senescence, and apoptosis are well accepted as the major checkpoints in stress responses, accumulating evidence implicates the importance of other tumor suppression mechanisms. (nature.com)
  • To date, various mechanisms have been suggested to explain the powerful tumor-suppressive effect of p53, including the induction of cell cycle arrest, senescence, and apoptosis. (nature.com)
  • It involves sabotaging one of the mechanisms that lingering senescent cells use in order to resist the fall into apoptosis, but which in normal cells has no important role to play. (fightaging.org)
  • Both these mechanisms work in addition to or independent from other well-known tumor suppressor mechanisms involving apoptosis. (sciencedaily.com)
  • This pitfall may be due to the lack of understanding of the mechanisms underlying chondrocyte senescence. (aging-us.com)
  • The least common outcome of mitotic catastrophe is senescence in which the cell stops dividing and enters a permanent cell cycle arrest that prevents the cell from proliferating any further. (wikipedia.org)
  • High concentrations of Salinomycin induced a G2 arrest, downregulation of survivin and triggered apoptosis. (uaeu.ac.ae)
  • Interestingly, treatment with low concentrations of Salinomycin induced a transient G1 arrest at earlier time point and G2 arrest at later point and senescence associatedwith enlarged cellmorphology, upregulation of p21 protein, increase in histone H3 and H4 hyperacetylation and expression of SA-β-Gal activity. (uaeu.ac.ae)
  • Everolimus specifically induced oncoprotein Tax degradation and senescence in ATL cells and cell cycle arrest and apoptosis in HTLV-I-negative malignant T-cells. (edu.lb)
  • Two powerful tumour suppressor pathways, controlled by the p53 and retinoblastoma (pRB) proteins, are important for establishing and maintaining the senescence growth arrest. (nature.com)
  • Is p53-dependent ferroptosis sufficient for tumor suppression in the absence of cell cycle arrest, senescence, and apoptosis? (nature.com)
  • In past due era mice and derivative cells, there is certainly improved genomic preservation and instability of p53-mediated senescence and apoptosis, resulting in serious cells degeneration and atrophy, premature ageing, and suppression of cancer compared with controls. (woofahs.com)
  • Susceptibility of activated T cells to apoptosis must be tightly regulated to ensure sufficient T cell progeny for an effective response, while allowing a rapid depletion of them at the end of the immune response. (nih.gov)
  • We show here that a previously isolated, NF-kappa B/rel target gene IEX-1 (Immediate Early response gene X-1) is highly expressed in T cells at early stages of activation, but declines with a prolonged period of activation time, coincident with an increased susceptibility of T cells to apoptosis during the late phases of an immune response. (nih.gov)
  • Transgenic expression of IEX-1 specifically in lymphocytes impaired apoptosis in activated T cells, extended a duration of an effector-phase of a specific immune response, and increased the accumulation of effector/memory-like T cells and the susceptibility to a lupus-like autoimmune disease. (nih.gov)
  • Cells that undergo mitotic catastrophe death can lack activation of pathways of the traditional death pathways such as apoptosis. (wikipedia.org)
  • Finally, we show that siRNA- or inhibitor-mediated blockade of integrin α6β4-Src-AKT signaling switches the post-irradiation fate from senescence to apoptosis, under p53 activated condition, in both cancer cells and tumor tissues of xenograft mice. (korea.ac.kr)
  • In mammalian organisms, cells that express markers of senescence have been shown to accumulate with age and at sites of certain age-related pathologies. (nature.com)
  • Increasing evidence indicates that senescent cells could be a promising new target for therapeutic intervention known as senotherapy, which includes depleting senescent cells, modulating SASP and restoration of senescence inhibitors. (frontiersin.org)
  • Unlike apoptosis, senescence is a state of which cells are still alive and metabolically active. (frontiersin.org)
  • In fact, several studies have shown that T2D induces senescence in multiple types of cells, including fibroblasts and endothelial cells ( 11 , 12 ). (frontiersin.org)
  • In the later generations, when telomeres are short, cells die via apoptosis or senescence. (hopkinsmedicine.org)
  • Apoptosis and other forms of cell death are required for trimming excess, expired and damaged cells. (hopkinsmedicine.org)
  • Although the senescent cells remain viable, they show typical changes with enlarged and flattened cell bodies, apoptosis resistance, increased activity of senescence-associated β -galactosidase (SA- β -gal), and upregulation of cyclin-dependent kinase (CDK) inhibitors including p16 INK4A , ARF proteins, and p21 [ 13 - 16 ]. (hindawi.com)
  • Alternatively, cells that sense injury or loss of mitochondrial integrity may undergo programmed cell death (apoptosis). (massgenomics.org)
  • Near all are destroyed, either through the programmed cell death mechanism of apoptosis , or by immune cells attracted by the signal molecules generated by senescent cells . (fightaging.org)
  • While senescence has short-term roles to play in tumor suppression, by shutting down the ability to replicate in potentially cancerous cells, and in wound healing , these cells have no clear and evident long-term use in the body. (fightaging.org)
  • By interfering with the FOXO4-p53 crosstalk, the peptide causes senescent cells to go through apoptosis, or cell suicide. (fightaging.org)
  • Human umbilical vein endothelial cells (HUVECs) senescence is closely associated with age-related cardiovascular diseases. (karger.com)
  • Both proteins are also involved in stopping cell division in older cells (senescence). (medlineplus.gov)
  • According to Soengas, the tumor suppressive mechanism induced by the ER in melanocytes with these cancer-causing mutations is premature senescence -- a form of "suspended animation" that stops the cell cycle and keeps cells from dividing, but doesn't kill them. (sciencedaily.com)
  • Our preliminary results indicate that exogenous high mobility group protein B1 (HMGB1), a key senescence-associated mediator, downregulates ACdase expression in Raw264.7 cells. (nova.edu)
  • SPIN1 ablation activates p53, suppresses cell growth, reduces clonogenic ability, and induces apoptosis of human cancer cells. (elifesciences.org)
  • One of them is the replicative aging of cells (senescence), which consists in the irreversible stopping of cell division at the G1 stage of the cell cycle. (vechnayamolodost.ru)
  • Inhibition of mammalian target of rapamycin signaling by everolimus induces senescence in adult T-cell leukemia-lymphoma and apoptosis in peripheral T-cell lymphomas. (edu.lb)
  • Follicular helper T cell signature of replicative exhaustion, apoptosis, and senescence in common variable immunodeficiency. (nih.gov)
  • While there are ongoing research projects to define new markers or causes of senescence, we do know that senescence can be induced by damage to DNA, shortening of telomeres (which are the protective caps at the end of DNA molecules), mitochondrial damage, and something called epigenetic factors, which refers to changes to our chromosomes that affect the way DNA is packaged and genes are expressed. (sens.org)
  • Everolimus-mediated apoptosis was also associated with an upregulation of p53 upregulated modulator of apoptosis (PUMA-α) proteins, an increase in Bax proteins and downregulation of Bcl-x(L) proteins in all tested HTLV-I-positive and -negative malignant cell lines. (edu.lb)
  • In ischemic heart tissue, senescence-associated β -galactosidase (SA- β -gal) activity and proteins (such as p16, p19, and p53) are significantly upregulated [ 6 ]. (hindawi.com)
  • Together, the germline and somatic mutations impair the function of proteins that regulate division and senescence, leading to uncontrolled cell growth and the formation of a melanoma. (medlineplus.gov)
  • The tested drug treatments reduced senescence and other ageing markers, further consolidating our approach as a screening platform. (biorxiv.org)
  • Puig A, Rancan L, Paredes SD, Carrasco A, Escames G, Vara E et al (2016) Melatonin decreases the expression of inflammation and apoptosis markers in the lung of a senescence-accelerated mice model. (springer.com)
  • Here, we focus more closely on ageing and senescence metrics in order to make information available for risk analysis non the least with COVID-19. (karger.com)
  • The p53-associated signaling pathway has been demonstrated to regulate hypoxia-induced apoptosis and senescence [ 5 ]. (hindawi.com)
  • The mechanism here is quite different, involving FOXO4's influence on p53 , but I wouldn't be surprised to see it turn out to be a part of the same system of inhibition of apoptosis. (fightaging.org)
  • In a previous study, Soengas and colleagues found that certain oncogenes use a different senescence mechanism, which doesn't activate the ER, to block the transformation of melanocytes. (sciencedaily.com)
  • Numerous harmful factors that affect the human body from birth to old age cause many disturbances, e.g., in the structure of the genome, inducing cell apoptosis and their degeneration, which leads to the development of many diseases, including cancer. (mdpi.com)
  • In this application, Specific Aim 1 will establish the role of HMGB1 in ceramide accumulation in cytoplasm of senescence osteoclast precursors via downregulation of ACdase activity in vitro. (nova.edu)
  • On the other hand, etoposide treatment reliably induces DNA damage-related senescence in human articular chondrocytes evidenced by loss of proliferative capacity, DNA damage accumulation, and expression of some SASP components. (aging-us.com)
  • In this area, our recent research has included studying cutaneous shave biopsies for diagnosing primary colonic adenocarcinoma as well as growth inhibition and apoptosis in human brain tumor cell lines using selenium. (hopkinsmedicine.org)
  • While developmental senescence and acute senescence may positively contribute to the fine-tuning of embryogenesis and injury repair, chronic senescence, when unresolved promptly, plays a crucial role in kidney fibrogenesis and CKD progression. (frontiersin.org)
  • These pathways respond to somewhat different stimuli but interact and cooperate to control the senescence response. (nature.com)
  • Figure 4: Senescence controlled by the p53 and p16-pRB pathways. (nature.com)
  • Male young and old senescence-accelerated prone mice (SAMP8), aged 2 and 10 months, respectively, were divided into four groups: non-treated young, non-treated old, old treated with 1 mg/kg/day xanthohumol, and old treated with 5 mg/kg/day xanthohumol. (springer.com)
  • Male senescence-accelerated resistant mice (SAMR1) were used as controls. (springer.com)
  • It works by blocking the ability of a protein implicated in senescence, FOXO4, to tell another protein, p53, not to cause the cell to self-destruct. (fightaging.org)
  • The p53 protein is an important tumor suppressor that is essential for regulating cell division, senescence, and self-destruction (apoptosis). (medlineplus.gov)
  • Aravinthan A, Alexander G (2016) Senescence in chronic liver disease: is the future in ageing? (springer.com)
  • In in vitro experiment, RSV prevented hypoxia-induced NRCM senescence and apoptosis. (hindawi.com)
  • Our findings revealed that RSV protected against ischemia-induced mouse heart injury in vivo and hypoxia-induced NRCM injury in vitro via regulating Sirt1/p53-mediated cell senescence and inhibiting NLRP3-mediated inflammasome activation. (hindawi.com)
  • Lastly, we will explore the current therapeutic approaches and challenges in targeting senescence. (frontiersin.org)
  • 1632 remedy, even at a higher dose, did not drastically enhance apoptosis or senescence (Figures S8 and S9), suggesting that the inhibitory effects of C1632 on colony formation are not because of cytotoxicity-induced cell death. (emlinhibitor.com)
  • They can trigger apoptosis, a process of programmed cell death, when a cell becomes irreparably damaged or poses a risk of becoming cancerous. (pharmiweb.com)
  • There is a scheme of voluntary death in nature, or programmed cell death, the apoptosis. (unexplainable.net)
  • The academician, however, is certain that senescence and death is a program that nature "downloaded" in the genes. (unexplainable.net)
  • This programmed death, called apoptosis, is a kind of cell suicide. (msdmanuals.com)
  • The best option would be for a cell to successfully repair any damage that occurs, but when this isn't possible (and the damage hasn't reached a critical level of inducing apoptosis) a cell will become senescent to try and avoid becoming cancerous. (sens.org)