ApoptosisSecretory phenotypeExpression of senescence markersPhenotypeReplicativeArrestPrematureEpithelial cellsSenescent cellsVitroMitochondrialInhibitorsPathogenesisMechanismsTumorigenesisGenomeSASPTelomereDegradationInflammationEndothelialPlays a crucial roleTranscriptionalMarkersAgingTumor suppressionMammalianAcuteStimuliContributesDamageHepaticTherapeuticIntegrinChronic exposureProteinsStressesExogenousMechanismInsightsExposurePathophysiologyProliferation
Apoptosis14
- 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)
- The aim of this study was to investigate whether resveratrol (RSV) could ameliorate ischemia- and hypoxia-associated cardiomyocyte apoptosis and injury via inhibiting senescence signaling and inflammasome activation. (hindawi.com)
- 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)
- In in vitro experiment, RSV prevented hypoxia-induced NRCM senescence and apoptosis. (hindawi.com)
- The p53-associated signaling pathway has been demonstrated to regulate hypoxia-induced apoptosis and senescence [ 5 ]. (hindawi.com)
- Unlike apoptosis, senescence is a state of which cells are still alive and metabolically active. (frontiersin.org)
- Duncan , C.J.A. et al "Reduced eosinophil apoptosis in induced sputum correlates with asthma severity. (ersjournals.com)
- The aim of the present investigation was to elucidate the cellular mechanisms whereby Tanshinone IIA (Tan IIA) leads to cell cycle arrest and apoptosis in vitro in keratinocytes, the target cells in psoriasis. (hindawi.com)
- Tan IIA inhibited proliferation of mouse keratinocytes in a dose- and time-dependent manner and induced apoptosis, resulting in S phase arrest accompanied by down-regulation of pCdk2 and cyclin A protein expression. (hindawi.com)
- Furthermore, Tan IIA-induced apoptosis and mitochondrial membrane potential changes were also further demonstrated by DNA fragmentation, single-cell gel electrophoresis assay (SCGE), and flow cytometry methods. (hindawi.com)
- There was also no translocation of apoptosis-inducing factor (AIF) from mitochondria to the nucleus in apoptotic keratinocytes, indicating Tan IIA-induced apoptosis occurs mainly through the caspase pathway. (hindawi.com)
- SPIN1 ablation activates p53, suppresses cell growth, reduces clonogenic ability, and induces apoptosis of human cancer cells. (elifesciences.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)
- Cada célula está programada para realizar determinado número de divisiones celulares y, al finalizar dicho tiempo, la proliferación se interrumpe y la célula entra en un estado de inactividad tras el cual se produce la MUERTE CELULAR a través del proceso de APOPTOSIS. (bvsalud.org)
Secretory phenotype4
- PAI-1 can also be a component of the senescence-associated secretory phenotype (SASP). (wikipedia.org)
- 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)
- 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)
- Senescent cells secrete pro-inflammatory factors, metalloproteinases , and other proteins, collectively termed the senescence-associated secretory phenotype (SASP) . (fightaging.org)
Expression of senescence markers1
- 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)
Phenotype1
- Figure 1: The senescent phenotype induced by multiple stimuli. (nature.com)
Replicative3
- We demonstrated mitochondrial dysfunction in replicative senescence -induced ARPE-19 cells after repeated passage . (fightaging.org)
- We demonstrate that replicative senescence, a tumor suppressor mechanism and guardian of genome stability, sometimes requires genomic instability to initiate its own action," the authors said. (genengnews.com)
- Replicative senescence is a cellular program preventing further cell divisions once telomeres become critically short . (fightaging.org)
Arrest12
- Senescence is a stress-response cellular state characterised by proliferative arrest but active metabolism ( 7 ). (frontiersin.org)
- 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)
- Proliferating cells can initiate an additional response by adopting a state of permanent cell-cycle arrest that is termed cellular senescence. (nature.com)
- Cellular senescence refers to an irreversible growth arrest that is triggered by various intrinsic and extrinsic stresses. (korea.ac.kr)
- 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)
- 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)
- Cellular senescence is characterized by an irreversible and permanent cell cycle arrest coupled with altered transcriptome and secretome. (frontiersin.org)
- However, WSC induced cell cycle arrest and cellular senescence mediated by the p53-p21 pathway. (nih.gov)
- INK4a and INK4b are induced by oncogenic Ras and are involved in cell cycle G1 arrest and cellular senescence. (sigmaaldrich.com)
- A team of cancer scientists led by Francis Rodier, PhD, a professor at the University of Montréal, has updated the current model of cellular senescence by providing evidence that the aging-related arrest of DNA replication is caused by irreversible damage to the genome rather than simply by an erosion of telomeres. (genengnews.com)
- Francis Rodier, PhD, and Marc-Alexandre Olivier [Source: CRCHUM] These findings improve upon the widely accepted scientific model of cellular aging that holds, telomeric ends erode with each cell division and trigger an arrest of cell division once they get too short, preventing further damage of the DNA code. (genengnews.com)
- The arrest of cell division related to cellular aging prevents cells with unstable genomes from multiplying and is a key mechanism in suppressing cancer. (genengnews.com)
Premature4
- 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)
- 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)
- 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)
- 13 Thus, the application of radiation therapy following surgery appears to prevent keloid scar recurrence by decreasing fibroblast proliferation, arresting the cell cycle and inducing premature cellular senescence. (jcadonline.com)
Epithelial cells2
- Bleomycin induces cellular senescence in alveolar epithelial cells. (ersjournals.com)
- Here, we present robust SWCNT-, MWCNT-, ASB- and UFCB-induced specific gene marker sets for in vitro chronically exposed lung epithelial cells. (cdc.gov)
Senescent cells6
- 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)
- They also conclude that this study provides proof of concept that senescent cells contribute to obesity-induced anxiety and that senolytics may offer a potential new way for treating neuropsychiatric disorders. (nih.gov)
- Researchers here report on in vitro experiments to show that introducing functional mitochondria into a cell culture containing senescent cells reduces markers of senescence. (fightaging.org)
- Those groups are not specifically targeting cellular senescence, but can hardly avoid having senescent cells taking up their therapeutic mitochondria. (fightaging.org)
- The model also suggests that strategies targeted at repairing telomeres in pre-senescent cells could eradicate telomere-induced DNA damage foci and low-level DNA damage response while preventing further irreversible damage to the genome. (genengnews.com)
- There is a strong connection between the phenomenon of cellular senescence and cancer research, through scientists in that field have generally been interested in generating more senescent cells rather than fewer of them. (fightaging.org)
Vitro6
- 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)
- In this manuscript, we report the in vitro mutagenicity of waterpipe smoke condensate (WSC), the alteration in cellular parameters of lung alveolar cells in response to WSC exposure and discuss the implication of cellular responses in the pathophysiology of chronic obstructive pulmonary disease (COPD). (nih.gov)
- The data reported here represent the first in vitro demonstration of the effect of waterpipe smoke on cellular parameters providing evidence of the potential involvement of WPS in the pathogenesis of COPD through impairing cellular growth and inducing inflammation. (nih.gov)
- Stem cell senescence in the in vitro expansion stage is an essential concern in clinical procedures of cell therapy. (magiran.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)
- In Specific Aim 2, we will elucidate the molecular mechanisms underlying ceramide-mediated fusion of senescent osteoclast precursors in vitro through a cathepsin B-induced Myh9 degradation pathway. (nova.edu)
Mitochondrial6
- Finally, we discuss how certain hallmarks of ageing (epigenetic alterations, mitochondrial dysfunction, telomere attrition, cellular senescence, and altered intercellular communication) predispose the ageing population to severe COVID-19. (ersjournals.com)
- A previous study has reported that MSC-derived mitochondrial transplantation protects the cornea against oxidative stress -induced mitochondrial damage. (fightaging.org)
- Here, we investigated the effects of extrinsic mitochondrial transplantation on senescence-induced ARPE-19 cells, an RPE cell line. (fightaging.org)
- Exogenous mitochondrial transplantation improved mitochondrial dysfunction and alleviated cellular senescence hallmarks, such as increased cell size, increased senescence-associated β-galactosidase activity, augmented NF-κB activity, increased inflammatory cytokines , and upregulated the cyclin-dependent kinase inhibitors p21 and p16 . (fightaging.org)
- Further, cellular senescence properties were improved by exogenous mitochondrial transplantation in oxidative stress -induced senescent ARPE-19 cells. (fightaging.org)
- These results indicate that exogenous mitochondrial transplantation modulates cellular senescence and may be considered a novel therapeutic strategy for AMD. (fightaging.org)
Inhibitors1
- The INK and CIP/KIP families of cyclin dependent kinase inhibitors (CDKis) protect cells from oncogenic signals-initiated cellular transformation. (sigmaaldrich.com)
Pathogenesis6
- 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)
- The coronavirus disease 2019 (COVID-19) pandemic has elicited a swift response by the scientific community to elucidate the pathogenesis of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2)-induced lung injury and develop effective therapeutics. (ersjournals.com)
- In this review we connect the current understanding of the SARS-CoV-2 replication cycle and host response to the clinical presentation of COVID-19, borrowing concepts from influenza A virus-induced ARDS pathogenesis and discussing how these ideas inform our evolving understanding of COVID-19-induced ARDS. (ersjournals.com)
- Our review explores influenza A virus-induced acute respiratory distress syndrome (ARDS) as a paradigm for understanding coronavirus disease 2019 (COVID-19)-induced ARDS pathogenesis and ageing as a risk factor for severe disease. (ersjournals.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)
- 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)
Mechanisms6
- This pitfall may be due to the lack of understanding of the mechanisms underlying chondrocyte senescence. (aging-us.com)
- Cellular senescence is one of the main mechanisms involved [ 5 , 6 ]. (hindawi.com)
- By contrast, at a cellular "global" level PKA plays a major role downstream β1AR and results in an increase in LTCC current.Conclusions:Regulation of the LTCC activity by proximity coupling mechanisms occurs only via β2AR, but not β1AR. (imperial.ac.uk)
- Changes in cellular gene expression in response to small-molecule or genetic perturbations have yielded signatures that can connect unknown mechanisms of action (MoA) to ones previously established. (harvard.edu)
- Rahman is now a professor in the Department of Environmental Medicine at the University of Rochester Medical Center (URMC), where his research lab studies the cellular and molecular mechanisms involved in the development of chronic inflammatory lung diseases. (nih.gov)
- Although the current model accepts that telomeric uncapping triggers a telomeric DNA damage response that leads to senescence, the authors showed entry into senescence involves DNA repair mechanisms and a multistep relationship between irreversible telomeric and non-telomeric DNA damage, which control a transient unstable state and a stable state where cell division is arrested. (genengnews.com)
Tumorigenesis3
- More recently, cellular senescence has been considered as an additional cause of age-related tumorigenesis. (frontiersin.org)
- There is now substantial evidence that cellular senescence is a barrier to malignant tumorigenesis in vivo . (nature.com)
- Knockdown of inwardly rectifying potassium channel Kir2.2 suppresses tumorigenesis by inducing reactive oxygen species-mediated cellular senescence. (nih.gov)
Genome3
- The well-documented tumor suppressor p53, referred as 'the guardian of the genome', is activated upon exposure to a myriad of cellular stresses. (elifesciences.org)
- The study is reported in an article in the journal Nucleic Acids Research, titled, " Homologous recombination-mediated irreversible genome damage underlies telomere-induced senescence . (genengnews.com)
- This updated model offers a new basis for stress- or age-associated genome damage and indicates, cells that escape telomere-mediated senescence harbor irreparable genome damage. (genengnews.com)
SASP3
- 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)
- 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)
- This is thought to drive senescence of neighboring cells via the SASP and the functional decline of tissues. (fightaging.org)
Telomere4
- Figure 2: Telomere-dependent senescence. (nature.com)
- The new multistep model for entry into telomere-mediated senescence presented in the current study reconciles observations of senescence-associated genomic instability with observations that telomere breaks are largely irreparable and that cells can tolerate telomere-induced DNA damage foci (TIF) during an unstable "pre-senescent" state. (genengnews.com)
- 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)
- [ 18 ] Loss of DKC1 has been reported to induce oxidative stress independent of telomere shortening. (medscape.com)
Degradation1
- SARS-CoV-2 infection induces DNA damage, through CHK1 degradation and impaired 53BP1 recruitment, and cellular senescence. (cdc.gov)
Inflammation4
- This age-related inflammation, also referred to as inflammaging, increases the risk for tissue damage and genetic aberrations that cause cellular transformation and cancer development ( 8 , 9 ). (frontiersin.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)
- Acute or chronic inflammation induced by ischemia has also been suggested to play an important role in the process of malignant cardiac remodeling [ 3 ]. (hindawi.com)
- With consistent NIH funding since 2007, he has studied how environmental tobacco smoke induces inflammation by disrupting biological processes known as circadian rhythms. (nih.gov)
Endothelial2
- In fact, several studies have shown that T2D induces senescence in multiple types of cells, including fibroblasts and endothelial cells ( 11 , 12 ). (frontiersin.org)
- Our investigation indicates that most of these studies examined endothelial progenitor cells, hematopoietic stem cells, mesenchymal stem cells, adipose-derived stem cells, and a few others were about less-discussed types of stem cells such as cardiac stem cells, myeloblasts, and induced pluripotent stem cells. (magiran.com)
Plays a crucial role2
- 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)
- 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)
Transcriptional2
- These experiments reveal a previously unappreciated role for transcriptional fidelity in cellular health and aging. (nih.gov)
- Also our study indicated that WSC induced an increase in the transcriptional expression of matrix metalloproteinases, MMP-2 and MMP-9 and an immune response regulator, Toll Like Receptor-4. (nih.gov)
Markers3
- 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)
- 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)
- Both SWCNT and MWCNT markers were associated with lipid metabolism and cancer while ASB and UFCB centered on inflammatory response and senescence, respectively. (cdc.gov)
Aging7
- In addition to the aging phenomenon, stem cell senescence has been investigated in various concepts such as cancer, adverse drug effects, and as a limiting factor in cell therapy. (magiran.com)
- Our current understanding of cellular aging rests upon the uncapping of the repetitive, non-protein-coding extremities of our linear chromosomes called telomeres. (genengnews.com)
- Aged, nondividing cells however continue to play an array of biological roles and their accumulation in tissues over time compromises tissue functions, linking cellular aging to organismal aging and cancer. (genengnews.com)
- The traditional model of cellular aging is unable to reconcile all observations in the aging cell. (genengnews.com)
- Genetically, we were able to reproduce the phenomenon of cellular aging in the laboratory and ensured that all the telomeres of a population of cells became dysfunctional," said PhD student Marc-Alexandre Olivier, co-first author of the study with former colleague Sabrina Ghadaouia, PhD, currently pursuing postdoctoral studies in England. (genengnews.com)
- Thus, the increase in cellular senescence that occurs with aging appears to play a major role in driving life-limiting age-related diseases. (fightaging.org)
- Intrinsic aging or senescence occurs silently from within starting at the molecular level, in the same sense that termites, if unchecked, will, sooner or later, destroy the structural integrity of even the largest wooden house. (agemed.org)
Tumor suppression1
- Sager, R. Senescence as a mode of tumor suppression. (nature.com)
Mammalian1
- Relief of delayed oxidative stress by ascorbic acid can suppress radiation-induced cellular senescence in mammalian fibroblast cells. (logosbio.com.cn)
Acute2
- Clinical data indicate that severe COVID-19 most commonly manifests as viral pneumonia-induced acute respiratory distress syndrome (ARDS), a clinical entity mechanistically understood best in the context of influenza A virus-induced pneumonia. (ersjournals.com)
- induced by CD4 + and CD8 + T cells stimulated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike epitopes (Ag2), levels were highest at 3 weeks after the second vaccination (6 W) and decreased by 37.4% at 3 months (4 M) and 60.0% at 6 months (7 M), the decline of which seemed slower than that of anti-spike antibody levels. (cdc.gov)
Stimuli2
- Many stimuli elicit a senescence response. (nature.com)
- These pathways respond to somewhat different stimuli but interact and cooperate to control the senescence response. (nature.com)
Contributes1
- There is also mounting evidence that cellular senescence contributes to ageing. (nature.com)
Damage3
- This telomeric uncapping triggers a continuous DNA Damage Response (DDR) that induces a stable state of cellular senescence accompanied by a complete suspension of cell division. (genengnews.com)
- It cannot help in determining the cellular threshold for the number of dysfunctional telomeres that causes cells to stop dividing due to persistent DNA damage response signaling. (genengnews.com)
- Senescence can be induced by DNA DAMAGE or other cellular stresses, such as OXIDATIVE STRESS. (bvsalud.org)
Hepatic1
- This study aimed to evaluate the effects of TQ on spatial memory and hippocampal long-term potentiation (LTP) in rats with thioacetamide (TAA)-induced liver injury and hepatic encephalopathy. (magiran.com)
Therapeutic2
- Lastly, we will explore the current therapeutic approaches and challenges in targeting senescence. (frontiersin.org)
- 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)
Integrin3
- Here we show that the activation of integrin β4 is essential for IR-induced cellular senescence. (korea.ac.kr)
- We further reveal that the IR-induced phosphorylation of integrin β4 is regulated by the cholesterol content and membrane fluidity. (korea.ac.kr)
- We also find that IR-induced p53-caspase signaling is independent of integrin α6β4-Src-AKT signaling. (korea.ac.kr)
Chronic exposure1
- Lentigos similar to PUVA freckles have cellular senescence may be chronic exposure to been reported to be induced by exposure to tan- oxidative stress. (who.int)
Proteins1
- 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)
Stresses1
- Senescence also can be induced by cellular stress, including oxidative and genotoxic stresses, or by activation of certain oncogenes . (fightaging.org)
Exogenous1
- 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)
Mechanism2
- Campisi, J. Cellular senescence as a tumor-suppressor mechanism. (nature.com)
- In this review, we discuss current understanding of the role and mechanism of cellular senescence in kidney fibrosis. (frontiersin.org)
Insights1
- 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)
Exposure1
- 1999). Experimental studies on UV exposure and senescence) and from increased expression of photo-ageing have been reviewed (IARC, 1992). (who.int)
Pathophysiology1
- Integrating established knowledge of influenza A virus-induced ARDS pathophysiology, we discuss how shared clinical findings frame influenza as only an approximate model for COVID-19. (ersjournals.com)
Proliferation1
- Cellular senescence is a multifaceted process that arrests the proliferation of cells that are at risk of neoplastic transformation. (nature.com)