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Arabidopsis WRKY45 Interacts with the DELLA Protein RGL1 to Positively Regulate Age- Triaaered Leaf senescence

Molecular Plant 2017年第9期10卷 1174-1189页

作者： Ligang Chen Key Laboratory of Tropical Plant Resources and Sustainable Use Xishuangbanna Tropical Botanical Garden Chinese Academy of Sciences Kunming Yunnan 650223 Chin University of Chinese Academy of Sciences Beijing 100049 China

Leaf senescence can be triggered and promoted by various environmental stressors, developmental cues, and endogenous hormone signals. Several lines of evidence have suggested the involvement of WRKY transcription factors in regulating leaf senescence, but the underlying mechanisms and signaling pathways involved remain elusive. In this study, we identified Arabidopsis thaliana WRKY DNA-binding protein 45 （WRKY45） as a positive regulator of age-triggered leaf senescence. Loss of W^KY45 function resulted in increased leaf longevity in age-triggered senescence, whereas overexpression of WRKY45 significantly accelerated age-triggered leaf senescence. Consistently, expression of senescence- ASSOCIATED GENEs （SAGs） was significantly reduced in wrky45 mutants but markedly enhanced in transgenic plants overexpressing WRKY45. Chromatin immunoprecipitation assays revealed that WRKY45 directly binds the promoters of several SAGs such as SAG12, SAG13, SAG113, and SEN4. Both in vivo and in vitro biochemical analyses demonstrated that WRKY45 interacts with the DELLA pro- tein RGA-LIKE1 （RGL1）, a repressor of the gibberellin （GA） signaling pathway. We found that RGL1 repressed the transcription activation function of WRKY45, thereby attenuating the expression of its reg- ulon. Consistent with this finding, overexpression of RGL1 resulted in significantly increased leaf longevity in age-triggered senescence. Taken together, our results provide compelling evidence that WRKY45 functions as a critical component of the GA-mediated signaling pathway to positively regulate age-triggered leaf senescence.

关键词： senescence WRKY transcription factor DELLA protein gibberellin

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Effects of post-silking water deficit on the leaf photosynthesis and senescence of waxy maize

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Journal of Integrative Agriculture 2020年第9期19卷 2216-2228页

作者： YE Yu-xiu WEN Zhang-rong YANG Huan LU Wei-ping LU Da-lei Jiangsu Key Laboratory of Crop Genetics and Physiology/Jiangsu Key Laboratory of Crop Cultivation and Physiology/Agricultural College Yangzhou University/Jiangsu Co-Innovation Center for Modern Production Technology of Grain CropsYangzhou 225009P.R.China Huaihai Institute of Technology Huai'an 222005P.R.China

Waxy maize is widely cultivated under rainfed conditions and frequently suffers water shortage during the late growth stage.In this study,a pot trial was conducted to examine the effects of post-silking drought on leaf photosynthesis and senescence and its influence on grain yield.Two waxy maize hybrids,Suyunuo 5(SYN5)and Yunuo 7(YN7),were grown under the control and drought(soil moisture content was 70–80%and 50–60%,respectively)conditions after silking in 2016 and 2017.The decrease in yield was 11.1 and 15.4%for YN7 and SYN5,respectively,owing to the decreased grain weight and number.Post-silking dry matter accumulation was reduced by 27.2%in YN7 and 26.3%in SYN5.The contribution rate of pre-silking photoassimilates transferred to grain yield was increased by 15.6%in YN7 and 10.2%in SYN5,respectively.Post-silking drought increased the malondialdehyde content,but decreased the contents of water,soluble protein,chlorophyll,and carotenoid in the leaves.The weakened activities of enzymes involved in photosynthesis(ribulose-1,5-bisphosphate carboxylase and phosphoenolpyruvate carboxylase)and antioxidant system(catalase,superoxide dismutase and peroxidase)reduced the photosynthetic rate(Pn)and accelerated leaf senescence.The correlation results indicated that reduced Pn and catalase activity and increased malondialdehyde content under drought conditions induced the decrease of post-silking photoassimilates deposition,ultimately resulted in the grain yield loss.

关键词： water deficit waxy maize photosynthesis antioxidant enzyme senescence dry matter accumulation

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3D TECA hydrogel reduces cellular senescence and enhances fibroblasts migration in wound healing

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Asian Journal of Pharmaceutical Sciences 2018年第4期13卷 317-325页

作者： Luay Thanoon Younis Mohamed Ibrahim Abu Hassan Tara Bai Taiyeb Ali Tommy Julianto Bustami Faculty of Dentistry Universiti Teknologi MARA Faculty of Dentistry Universiti Teknologi MARAMAHSA University Faculty of Pharmacy

This study was designed to investigate the effect of 3 D TECA hydrogel on the inflammatory-induced senescence marker, and to assess the influence of the gel on the periodontal lig-ament fibroblasts(PDLFs) migration in wound healing in vitro. PDLFs were cultured with20 ng/ml TNF-α to induce inflammation in the presence and absence of 50 μM 3 D TECA gelfor 14 d. The gel effect on the senescence maker secretory associated-β-galactosidase(SA-β-gal) activity was measured by a histochemical staining. Chromatin condensation and DNAsynthesis of the cells were assessed by 4,6-diamidino-2-phenylindole and 5-ethynyl-2-deoxyuridine fluorescent staining respectively. For evaluating fibroblasts migration, scratchwound healing assay and Pro-Plus Imaging software were used. The activity of senescencemarker, SA-β-gal, was positive in the samples with TNF-α-induced inflammation. SA-β-galpercentage is suppressed( > 65%, P senescence and enhancedfibroblasts proliferation and migration. Therefore, 3 D TECA may be used as an adjunct to ac-celerate repair and healing of periodontal tissues.

关键词： 3D TECA Cellular senescence SA-β-gal TNF-α Fibroblast migration

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Amyloid 13 Protein Aggravates Neuronal senescence an, d Cognitive Deficits in 5XFAD Mouse Model of Alzheimer s Disease

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Chinese Medical Journal 2016年第15期129卷 1835-1844页

作者： Zhen Wei Xiao-Chun Chen Yue Song Xiao-Dong Pan Xiao-Man Dai Jing Zhang Xiao-Li CUI Xi-Lin Wu Yuan-Gui Zhu Department of Neurology Fujian Medical University Union Hospital Fuzhou Fujian 350001 China Fujian Institute of Geriatrics Fujian Medical University Union Hospital Fuzhou Fujian 350001 China Key Laboratory of Brain Aging and NeurodegenerativeDiseases Fujian KeyLaboratory of Molecular Neurology Fujian Medical University Fuzhou Fujian 350001 China

Background： Amyloid β （Aβ） has been established as a key factor for the pathological changes in the brains of patients with Alzheimer＇s disease （AD）, and cellular senescence is closely associated with aging and cognitive impairment. However, it remains blurred whether, in theAD brains, Aβ accelerates the neuronal senescence and whether this senescence, in turn, impairs the cognitive function. This study aimed to explore the expression of senescence-associated genes in the hippocampal tissue from young to aged 5XFAD mice and their age-matched wild type （WT） mice to determine whether senescent neurons are present in the transgenic AD mouse model. Methods： The 5XFAD mice and age-matched wild type mice, both raised from 1 to 18 months, were enrolled in the study. The senescence-associated genes in the hippocampus were analyzed and differentially expressed genes （DEGs） were screened by quantitative real-time polymerase chain reaction. Cognitive perfom3ance of the mice was evaluated by Y-maze and Morris water maze tests. Oligomeric Aβ（oAβ）（1-42） was applied to culture primary neurons to simulate the in vivo manifestation. Aging-related proteins were detected by Western blotting analysis and immunofluorescence. Results： In 5XFAD mice, of all the DEGs, the senescence-associated marker p16 was most significantly increased, even at the early age. It was mainly localized in neurons, with a marginal expression in astrocytes （labeled as glutamine synthetase）, nil expression in activated microglia （labeled as lba1）, and negatively correlated with the spatial cognitive impairments of 5XFAD mice. oAβ （1-42） induced the production of senescence-related protein p1 6, but not p53 in vitro, which was in line with the in vivo manifestation. Conclusions： oAβ-accelerated neuronal senescence may be associated with the cognitive impairment in 5XFAD mice. senescence-associated marker p16 can serve as an indicator to estimate the cognitive prognosis for A D population.

关键词： Alzheimer＇s Disease Amyloid β Cognition P 16 senescence

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Loss of IKB kinase βpromotes myofibroblast transformation and senescence through activation of the ROS-TGFβ autocrine loop

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Protein & Cell 2016年第5期7卷 338-350页

作者： Liang Chen Zhimin Peng Qinghang Meng Maureen Mongan Jingcai Wang Maureen Sartor Jing-Chen Liang Niu Mario Medvedovic Winston Kao Ying Xia Department of Environmental Health and Center of Environmental Genetics University of Cincinnati Medical Center Cincinnati OH 45267 USA Department of Ophthalmology University of Cincinnati Medical Center Cincinnati OH 45267 USA

Using forward and reverse genetics and global gene expression analyses, we explored the crosstalk between the IKB kinase β （IKKβ） and the transforming growth factor β （TGFβ） signaling pathways. We show that in vitro ablation of Ikkβ in fibroblasts led to progressive ROS accumulation and TGFβ activation, and ultimately accelerated cell migration, fibroblast-myofibroblast transformation and senescence. Mechanistically, the basal IKKβ activity was required for anti-oxidant gene expression and redox homeostasis. Lacking this activity, IKKβ-null cells showed ROS accumulation and activation of stress-sensitive transcription factor AP-1/c- Jun. AP-1/c-Jun activation led to up-regulation of the Tgfβ2 promoter, which in turn further potentiated intracellular ROS through the induction of NADPH oxidase （NOX）. These data suggest that by blocking the autocrine amplification of a ROS-TGFβ loop IKKβ plays a crucial role in the prevention of fibroblast-myofibroblast transformation and senescence.

关键词： IkB kinase β （IKKβ） nuclear factor KB （NF-KB） transforming growth factors β （TGFβ） reactive oxygenspecies （ROS） myofibroblast senescence

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Sugar Starvation Enhances Leaf senescence and Genes Involved in Sugar Signaling Pathways Regulate Early Leaf senescence in Mutant Rice

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Rice science 2020年第3期27卷 201-214页

作者： LI Zhaowei ZHAO Qian CHENG Fangmin College of Life Sciences Fujian Agriculture and Forestry UniversityFuzhou 350002China Institute of Crop Science College of Agriculture and BiotechnologyZhejiang UniversityHangzhou 310058China

To clarify the complex regulatory relationship between changes in sugar content and leaf senescence during the grain-filling stage of rice,genotype-dependent differences in sugar content and the temporal transcriptional patterns of genes involved in sugar signaling pathways were determined in mutant rice exhibiting early leaf senescence and its wild type Zhefu 142.The effects of exogenous glucose or sucrose on the senescence of detached leaves under dark conditions were also investigated.Chlorophyll,soluble sugar,sucrose and fructose contents decreased,whereas electrolytic leakage and malondialdehyde levels increased in mutant leaves at the grain-filling stage.These results suggested that sugar starvation is positively correlated with the early leaf senescence of mutant plants.Detached leaf segments incubated in exogenous sugar solutions under dark conditions exhibited delayed senescence.The high expression of Hxk1 in leaves of mutant plants at the initial grain-filling stage suggested that Hxk1 is involved in the hexose-sensing process at the early stage of leaf senescence.The low expression levels of Hxk2 and Frk1 in the senescing leaves of mutant rice during the grain-filling stage are indicative of weakened hexose phosphorylation.In addition,the high expression levels of Su Sy1,Su Sy2 and Su Sy4 in leaves of mutant plants at the initial grain-filling stage are accompanied by the high transcript levels of SUT1,which favor sucrose translocation and remobilization from the early senescing leaves of mutant rice.The relatively reduced transcript levels of ch FBP,cy FBP,SPS1,SPS2 and SPS6 indicated that during the grain-filling stage,sucrose biosynthesis is weakened in the senescing leaves of mutant rice.

关键词： rice sugar starvation leaf senescence signaling pathway detached leaf segment grain-filling stage

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A single-nucleus transcriptomic atlas of primate liver aging uncovers the pro-senescence role of SREBP2 in hepatocytes

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Protein & Cell 2024年第2期15卷 98-120页

作者： Shanshan Yang Chengyu Liu Mengmeng Jiang Xiaoqian Liu Lingling Geng Yiyuan Zhang Shuhui Sun Kang Wang jian Yin Shuai Ma Si Wang Juan Carlos Izpisua Belmonte Weiqi Zhang Jing Qu Guang-Hui Liu Advanced Innovation Center for Human Brain Protection and National Clinical Research Center for Geriatric Disorders Xuanwu Hospital Capital Medical UniversityBeijing 100053China State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Aging Translational Medicine Center International Center for Aging and CancerBeijing Municipal Geriatric Medical Research CenterXuanwu HospitalCapital Medical UniversityBeijing 100053China State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijing 100101China Xuanwu Hospital Capital Medical University Beijing 100053China University of Chinese Academy of Sciences Beijing 100049China Institute for Stem Cell and Regeneration Chinese Academy of SciencesBeijing 100101China Beijing Institute for Stem Cell and Regenerative Medicine Beijing 100101China Aging Biomarker Consortium Beijing 100101China Altos Labs Inc.San DiegoCA 94022USA

Aging increases the risk ofliver diseases and systemic susceptibility to aging-related diseases.However,cell type-specific changes and the underlying mechanism of liver aging in higher vertebrates remain incompletely characterized.Here,we constructed the first single-nucleus transcriptomic landscape of primate liver aging,in which we resolved cell type-specific gene expression fluctuation in hepatocytes across three liver zonations and detected aberrant cell-cell interactions between hepatocytes and niche cells.Upon in-depth dissection of this rich dataset,we identifed impaired lipid metabolism and upregulation of chronic inflammation-related genes prominently associated with declined liver functions during aging.In particular,hyperactivated sterol regulatory element-binding protein(SREBP)signaling was a hallmark of the aged liver,and consequently,forced activation of SREBP2 in human primary hepatocytes recapitulated in vivo aging phenotypes,manifesting as impaired detoxification and accelerated cellular senescence.This study expands our knowledge of primate liver aging and informs the development of diagnostics and therapeutic interventions for liver aging and associated diseases.

关键词： single-nucleus RNA sequencing liver hepatocytes aging senescence SREBP2

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Variability and limits of nitrogen and phosphorus resorption during foliar senescence

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Plant Communications 2023年第2期4卷 41-55页

作者： Marc Estiarte Matteo Campioli Maria Mayol Josep Penuelas CSIC Global Ecology Unit CREAF-CSIC-UAB08193 BellaterraCataloniaSpain CREAF 08193 Cerdanyola del VallèsCataloniaSpain Research Group of Plant and Vegetation Ecology Department of BiologyUniversity of Antwerp2610 WilrijkBelgium

Foliar nutrient resorption(NuR)plays a key role in ecosystem functioning and plant nutrient economy.Most of this recycling occurs during the senescence of leaves and is actively addressed by cells.Here,we discuss the importance of cell biochemistry,physiology,and subcellular anatomy to condition the outcome of NuR at the cellular level and to explain the existence of limits to NuR.Nutrients are transferred from the leaf in simple metabolites that can be loaded into the phloem.Proteolysis is the main mechanism for mobilization of N,whereas P mobilization requires the involvement of different catabolic pathways,making the dynamics of P in leaves more variable than those of N before,during,and after foliar senescence.The biochemistry and fate of organelles during senescence impose constraints that limit NuR.The efficiency of NuR decreases,especially in evergreen species,as soil fertility increases,which is attributed to the relative costs of nutrient acquisition from soil decreasing with increasing soil nutrient availability,while the energetic costs of NuR from senescing leaves remain constant.NuR is genetically determined,with substantial interspecific variability,and is environmentally regulated in space and time,with nutrient availability being a key driver of intraspecific variability in NuR.

关键词： foliar nutrient resorption senescence nitrogen phosphorus efficiency nutrient availability

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hCINAP alleviates senescence by regulating MDM2 via p14ARF and the HDAC1/CoREST complex

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Journal of Molecular Cell Biology 2023年第2期15卷 58-71页

作者： Xinping Huang Yan Zhao Min Wei Ruipeng Zhuge Xiaofeng Zheng State Key Laboratory of Protein and Plant Gene Research School of Life SciencesPeking UniversityBeĳing 100871China Department of Biochemistry and Molecular Biology School of Life SciencesPeking UniversityBeĳing 100871China

Cellular senescence is a major process affected by multiple signals and coordinated by a complex signal response network.Identification of novel regulators of cellular senescence and elucidation of their molecular mechanisms will aid in the discoveryof new treatment strategies for aging-related diseases. In the present study, we identified human coilin-interacting nuclear ATPaseprotein (hCINAP) as a negative regulator of aging. Depletion of cCINAP significantly shortened the lifespan of Caenorhabditiselegans and accelerated primary cell aging. Moreover, mCINAP deletion markedly promoted organismal aging and stimulatedsenescence-associated secretory phenotype in the skeletal muscle and liver from mouse models of radiation-induced senescence.Mechanistically, hCINAP functions through regulating MDM2 status by distinct mechanisms. On the one hand, hCINAP decreasesp53 stability by attenuating the interaction between p14ARF and MDM2;on the other hand, hCINAP promotes MDM2 transcriptionvia inhibiting the deacetylation of H3K9ac in the MDM2 promoter by hindering the HDAC1/CoREST complex integrity. Collectively,our data demonstrate that hCINAP is a negative regulator of aging and provide insight into the molecular mechanisms underlyingthe aging process.

关键词： hCINAP HDAC1/CoREST complex p14ARF MDM2 transcription senescence

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SIRTain regulators of premature senescence and accelerated aging

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Protein & Cell 2015年第5期6卷 322-333页

作者： Shrestha Ghosh Zhongjun Zhou Department of Biochemistry The University of Hong Kong Hong Kong China Shenzhen Institute of Innovation and Technology The University of Hong Kong Hong Kong China

The sirtuin proteins constitute class III histone deacetylases （HDACs）. These evolutionarily conserved NAD＋-dependent enzymes form an important component in a variety of cellular and biological processes with highly divergent as well as convergent roles in maintaining metabolic homeostasis, safeguarding genomic integrity, regulating cancer metabolism and also inflammatory responses. Amongst the seven known mammalian sirtuin proteins, SIRT1 has gained much attention due to its widely acknowledged roles in pro- moting longevity and ameliorating age-associated pathologies. The contributions of other sirtuins in the field of aging are also gradually emerging. Here, we summarize some of the recent discoveries in sirtuins biology which clearly implicate the functions of sirtuin proteins in the regulation of premature cellular senescence and accelerated aging. The roles of sirtuins in various cellular processes have been extrapolated to draw inter-linkage with anti-aging mechanisms. Also, the latest findings on sirtuins which might have potential effects in the process of aging have been reviewed.

关键词： sirtuins senescence premature aging longevity

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