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)
In this work, we show that repeated stresses with UVB (290-320nm) induce stress-induced premature senescence (SIPS) of skin human diploid fibroblasts (HDFs). (unamur.be)
This model could be used to test whether HDFs in UVB-induced premature senescence are able to promote epithelial cell growth and tumorigenesis in skin, as shown recently with HDFs in H 2 O 2 -induced premature senescence. (unamur.be)
Deletion of AP4 causes premature senescence and defects in mitogen-induced proliferation in mouse embryonic fibroblasts (MEFs) [ 5 , 7 ]. (biomedcentral.com)
Numerous studies have revealed the critical role of premature senescence induced by various cancer treatment modalities in the pathogenesis of aging-related diseases. (oaepublish.com)
Growing evidence demonstrates that various cancer treatment modalities, including chemotherapy, radiation therapy, targeted therapy, immunotherapy, hormone therapy, stem cell or bone marrow transplant, and surgery [ 3 - 5 ] , cause premature senescence, as reviewed elsewhere [ 6 - 8 ] . (oaepublish.com)
In primary mammalian cells oncogenic induces premature senescence depending on an active MEK-extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK) pathway. (molecularcircuit.com)
Therefore oncogenic provokes premature senescence by activating the MEK-ERK and MKK3/6-p38 pathways in normal primary cells sequentially. (molecularcircuit.com)
These studies have got described the molecular occasions inside the signaling cascade that result in premature senescence and therefore have provided brand-new insights into how confers oncogenic change in major cells. (molecularcircuit.com)
Oddly enough the AP24534 power of oncogenic to induce premature senescence depends upon the Raf-MEK-ERK pathway that mediates cell proliferation (36). (molecularcircuit.com)
It continues to be unclear how activation from the mitogenic Raf-MEK-ERK pathway by can stimulate premature senescence and exactly how this harmful growth influence of is certainly bypassed in tumors. (molecularcircuit.com)
Ectopic expression of MEKK3 a MAPKKK that activates p38 induced G1 arrest and reversed induces premature senescence through sequential activation of the MEK-ERK pathway and the MKK3/6-p38 pathway in primary human fibroblasts. (molecularcircuit.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)
Cellular18
Cellular senescence is one of the main mechanisms involved [ 5 , 6 ]. (hindawi.com)
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)
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)
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)
Inactivation of AP4 in CRC cell lines resulted in increased spontaneous and c-MYC-induced DNA damage, chromosomal instability (CIN) and cellular senescence. (biomedcentral.com)
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)
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)
Lower levels of expression will influence relative activity and be insufficient to initiate tumorigenesis, whilst too much Ras will induce oncogenic stress. (nature.com)
Replicative senescence1
After 2 days of recovery, several biomarkers of replicative senescence were established. (unamur.be)
Secretory3
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)
These results indicate that the two intestinal secretory peptides antagonistically regulate adult lifespan and intestinal senescence through multiple pathways, irrespective of insulin, which implicates a complementary gradient distribution of each of the hormone-producing EEs, consistent with local requirements for cell activity along the posterior midgut. (bioone.org)
Apoptosis5
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)
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)
Pathogenesis3
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)
Therapeutic approaches1
Lastly, we will explore the current therapeutic approaches and challenges in targeting senescence. (frontiersin.org)
Chronic exposure2
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)
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)
Arrest1
This senescence-like development arrest induced by is certainly associated with deposition of development inhibitors such as for example p53 and p16INK4A (51). (molecularcircuit.com)
Lifespan1
However, gut senescence does not appear to be the direct cause for longevity regulation, as knockdown of both hormone receptors did not affect adult lifespan. (bioone.org)
Mechanisms1
This pitfall may be due to the lack of understanding of the mechanisms underlying chondrocyte senescence. (aging-us.com)
SASP1
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)
Genes1
Third, the steady-state level of the mRNA of three senescence-associated genes, i.e. fibronectin, osteonectin and SM22, was increased in HDFs at 72h after three and five exposures to UVB. (unamur.be)
Acute2
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)
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)
Tissue1
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)
Ectopic1
Inhibition of miR-22-3p or ectopic MDC1 expression reversed the increased senescence, DNA damage, CIN and defective HR observed in AP4 -deficient CRC cells. (biomedcentral.com)
Expression1
1999). Experimental studies on UV exposure and senescence) and from increased expression of photo-ageing have been reviewed (IARC, 1992). (who.int)
Cells1
First, there was an increase in the proportion of cells positive for senescence-associated β-galactosidase activity. (unamur.be)
Activation3
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)
Constitutive activation of the pathway induces p53 p21 and p16 and leads to early senescence. (molecularcircuit.com)
In addition does not induce senescence when the activation from the MEK-ERK pathway is certainly particularly inhibited. (molecularcircuit.com)
Damage2
In summary, AP4, miR-22-3p and MDC1 form a conserved and coherent, regulatory feed-forward loop to promote DNA repair, which suppresses DNA damage, senescence and CIN, and contributes to 5-FU resistance. (biomedcentral.com)
Telomeric DNA damage response induced by some cancer treatments can persist for months, possibly accounting for long-term sequelae of cancer treatments. (oaepublish.com)
Findings1
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)
Result1
This effect on longevity is apparently correlated with the midgut senescence phenotypes as a result of direct hormone action through both hormone receptors expressed in the enteroblasts or other midgut cell types. (bioone.org)
Independent2
We also find that IR-induced p53-caspase signaling is independent of integrin α6β4-Src-AKT signaling. (korea.ac.kr)
Furthermore, these senescence phenotypes appear to be independent of insulin signaling and manifest in an organ-specific manner. (bioone.org)
Content1
We further reveal that the IR-induced phosphorylation of integrin β4 is regulated by the cholesterol content and membrane fluidity. (korea.ac.kr)