• Asian Pacific Journal of Cancer Prevention
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• v.17 no.3
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• pp.957-963
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• 2016

Cellular senescence, a barrier to tumorigenesis, controls aberrant proliferation of cells. We here aimed to investigate cellular senescence in immortalized cholangiocyte and cholangiocarcinoma cell lines using five different inducing agents: 5-aza-2'deoxycytidine, bromodeoxyuridine, interferons ($IFN{\beta}$ and $IFN{\gamma}$), and hydrogen peroxide. We analyzed senescence characteristics, colony formation ability, expression of genes involved in cell cycling and interferon signaling pathways, and protein levels. Treatment with all five agents decreased cell proliferation and induced cellular senescence in immortalized cholangiocyte and cholangiocarcinoma cell lines with different degrees of growth-inhibitory effects depending on cell type and origin. Bromodeoxyuridine gave the strongest stimulus to inhibit growth and induce senescence in most cell lines tested. Expression of p21 and interferon related genes was upregulated in most conditions. The fact that bromodeoxyuridine had the strongest effects on growth inhibition and senescence induction implies that senescence in cholangiocarcinoma cells is likely controlled by DNA damage response pathways relating to the p53/p21 signaling. In addition, interferon signaling pathways may partly regulate this mechanism in cholangiocarcinoma cells.

• Proceedings of the Botanical Society of Korea Conference
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• 1996.07a
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• pp.19-25
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• 1996

Three key genetic loci required for proper progression of leaf senescence were identified in Arabidopsis thaliana. Mutations in these loci cause delay in all senescence symptoms examined, including both anabolic and catabolic activities, during natural senescence and upon artificial senescence induced by various senescence-inducing treatments. The result provides a decisive evidence that leaf senescence is a genetically programmed phenomenon controlled by several monogenic loci in Arabidopsis thaliana. The result further indicates that leaf senescence caused by various senescence signals occurs, at least in part, through common pathways in Arabidopsis and that the threed genetic loci function at the common steps.

• IMMUNE NETWORK
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• v.16 no.3
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• pp.183-188
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• 2016

Sirtuin family members with lysine deacetylase activity are known to play an important role in anti-aging and longevity. Cellular senescence is one of the hallmarks of aging, and downregulation of sirtuin is reported to induce premature senescence. In this study, we investigated the effects of small-molecule sirtuin inhibitors on cellular senescence. Various small molecules such as tenovin-1 and EX527 were employed for direct sirtuin activity inhibition. U251, SNB-75, and U87MG glioblastoma cells treated with sirtuin inhibitors exhibited phenotypes with nuclear enlargement. Furthermore, treatment of rat primary astrocytes with tenovin-1 also increased the size of the nucleus. The activity of senescence-associated β-galactosidase, a marker of cellular senescence, was induced by tenovin-1 and EX527 treatment in U87MG glioblastoma cells. Consistent with the senescent phenotype, treatment with tenovin-1 increased p53 expression in U87MG cells. This study demonstrated the senescence-inducing effect of sirtuin inhibitors, which are potentially useful tools for senescence research.

• IMMUNE NETWORK
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• v.16 no.5
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• pp.286-295
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• 2016

Cellular replicative senescence is a major contributing factor to aging and to the development and progression of aging-associated diseases. In this study, we sought to determine viral replication efficiency of influenza virus (IFV) and Varicella Zoster Virus (VZV) infection in senescent cells. Primary human bronchial epithelial cells (HBE) or human dermal fibroblasts (HDF) were allowed to undergo numbers of passages to induce replicative senescence. Induction of replicative senescence in cells was validated by positive senescence-associated b-galactosidase staining. Increased susceptibility to both IFV and VZV infection was observed in senescent HBE and HDF cells, respectively, resulting in higher numbers of plaque formation, along with the upregulation of major viral antigen expression than that in the non-senescent cells. Interestingly, mRNA fold induction level of virus-induced type I interferon (IFN) was attenuated by senescence, whereas IFN-mediated antiviral effect remained robust and potent in virus-infected senescent cells. Additionally, we show that a longevity-promoting gene, sirtuin 1 (SIRT1), has antiviral role against influenza virus infection. In conclusion, our data indicate that enhanced viral replication by cellular senescence could be due to senescence-mediated reduction of virus-induced type I IFN expression.

• BMB Reports
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• v.51 no.10
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• pp.493-499
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• 2018

Cellular senescence is a state of permanent cell-cycle arrest triggered by different internal and external stimuli. This phenomenon is considered to be both beneficial and detrimental depending on the cell types and biological contexts. During normal embryonic development and after tissue injury, cellular senescence is critical for tissue remodeling. In addition, this process is useful for arresting growth of tumor cells, particularly during early onset of tumorigenesis. However, accumulation of senescent cells decreases tissue regenerative capabilities and induces inflammation, which is responsible for cancer and organismal aging. Therefore cellular senescence has to be tightly regulated, and dysregulation might lead to the aging and human diseases. Among many regulators of cellular senescence, in this review, I will focus on microRNAs, small non-coding RNAs playing critical roles in diverse biological events including cellular senescence.

• Food Science of Animal Resources
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• v.40 no.1
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• pp.106-117
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• 2020

Cellular senescence is associated with age-related vascular disorders and has been implicated in vascular dysfunctions. Here, we show that duck oil-loaded nanoemulsion (DO-NE) attenuates premature senescence of vascular smooth muscle cells (VSMCs) triggered by angiotensin II (Ang II). Compared with control nanoemulsion (NE), DO-NE significantly inhibited the activity of senescence-associated β-galactosidase, which is a biomarker of cellular senescence, in Ang II-treated VSMCs. SIRT1 protein expression was dose- and time-dependently induced in VSMCs exposed to DO-NE, but not in those exposed to NE, and SIRT1 promoter activity was also elevated. Consistently, DO-NE also dose-dependently rescued Ang II-induced repression of SIRT1 expression, indicating that SIRT1 is linked to the anti-senescence action of DO-NE in VSMCs treated with Ang II. Furthermore, the SIRT1 agonist resveratrol potentiated the effects of DO-NE on VSMCs exposed to Ang II, whereas the SIRT1 inhibitor sirtinol elicited the opposite effect. These findings indicate that DO-NE inhibits senescence by upregulating SIRT1 and thereby impedes vascular aging triggered by Ang II.

• BMB Reports
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• v.49 no.11
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• pp.641-650
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• 2016

Cellular senescence is a process by which cells enter a state of permanent cell cycle arrest. It is commonly believed to underlie organismal aging and age-associated diseases. However, the mechanism by which cellular senescence contributes to aging and age-associated pathologies remains unclear. Recent studies showed that senescent cells exert detrimental effects on the tissue microenvironment, generating pathological facilitators or aggravators. The most significant environmental effector resulting from senescent cells is the senescence-associated secretory phenotype (SASP), which is constituted by a strikingly increased expression and secretion of diverse pro-inflammatory cytokines. Careful investigation into the components of SASPs and their mechanism of action, may improve our understanding of the pathological backgrounds of age-associated diseases. In this review, we focus on the differential expression of SASP-related genes, in addition to SASP components, during the progress of senescence. We also provide a perspective on the possible action mechanisms of SASP components, and potential contributions of SASP-expressing senescent cells, to age-associated pathologies.

• Journal of Life Science
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• v.11 no.1
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• pp.14-21
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• 2001

To investigate the changes of carbohydrate metabolism in the senescing leaves of Zea mays during dark-induced senescence, the changes in the contents of reducing sugar, sucrose and starch as well as the activities of sucrose synthase, three isozymes of invertase, and ${\alpha}$-amylase were measured. In the senescing leaves, the content of reducing sugars temporarily increased at 4 d and rapidly decreased thereafter, whereas sucrose contents gradually decreased thereafter, whereas sucrose contents gradually decreased until 3 d of senscence and significantly decreased thereafter. The activities of intracellular invertases such as soluble acid and alkaline formed gradually enhanced until 4 d of leaf senescence and significantly declined thereafter. The extracellular invertase activity showed no significant changes during leaf senescence. The deactivation of sucrose synthase was observed within 3 d of leaf senscence. On the other hand, the starch contents gradually declined during 2 d of leaf senescence, and showed a temporary increase at 3 d, which is similar to the pattern of sucrose synthase activity., These results imply that sucrose in the senescing leaves. The major enzymes which correlated to the breakdown of sucrose during dark-induced senescence were soluble acid and alkaline invertases, not sucrose and ABA accelerated leaf senescence by inducing the accumulation of reducing sugar. These result, therefore, that leaf senescence may be mediated by the temporary quantitative changes of reducing sugar induced by the activation of intracellualr inveertases.

• Environmental Sciences Bulletin of The Korean Environmental Sciences Society
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• v.2 no.1
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• pp.37-48
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• 1998

Effect of plant hormones on the leaf senescence of mung bean (Phaseolus radiatus) was investigated by measuring the changes of reducing sugar contents and invertase isozyme activities in detached leaves treated with NAA, $GA_3$ or BA. During dark-induced senescence, reducing sugar contents in the detached leaves increased temporarily at 4 d, thereafter decreased rapidly and reached minimum values within 7-14 d. The pattern of soluble acid invertase activity in the senescing leaves kept in the dark was similar to that of reducing sugar accumulation, whereas the activities of alkaline and extracellular invertases were not significantly changed during leaf senescence. Therefore, these results suggest that soluble acid invertase, but not alkaline and extracellular invertases, induces the accumulation of reducing sugar during leaf senescence of mung bean plants. Exogenous NAA application had little or no effect in the increase of soluble acid invertase activity during dark-induced senescence compared to the control. However, exogenous applications of $GA_3$ and BA led to the increase of soluble acid invertase activity in the senescing leaves. Particularly, BA application was very effective in enhancing the activity of soluble acid invertase as well as in delaying chlorophyll breakdown during dark-induced senescence. These results suggest, therefore, that BA regulates the activity of soluble acid invertase, which leads to the accumulation of reducing sugar, and the stability of photosynthetic apparatus to delay leaf senescence.

• KOREAN JOURNAL OF CROP SCIENCE
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• v.48 no.3
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• pp.224-231
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• 2003

This study was conducted to investigate the varietal differences in leaf senescence during ripening stage and its relation to grain yield of rice. During grain filling period leaf senescence was evaluated by SPAD readings (an indirect indicator of chlorophyll content) for 74 varieties including local, improved domestic, and introduced varieties in the field condition. Leaf senescence was varied greatly among 74 varieties. Jodongji and Dadajo known as local rice varieties had significantly lower SPAD value than the other varieties and became senescent rapidly. However, SPAD value of the flag leaf and 2nd leaf of SNU-SG1 were much higher than the other varieties and leaves of SNU-SG1 also showed a tendency of delayed senescence compared to the other varieties. There were significantly positive correlation between cumulated SPAD value of upper leaf(flag leaf and 2nd leaf) during 35 days after heading and grain yield divided by sunshine hour during 40 days of grain filling and compensated for temperature effect, and cumulated SPAD value of the 4th leaf showed negative correlation with the yield. That is, the delayed senescence of the upper leaves and the rapid senescence of lower leaves were positively associated with grain yield increase.