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Engineered Regeneration 2022年第4期3卷 365-373页

作者： Xuefeng Yao Huaqiong Li Liping Chen Lay Poh Tan School of Materials Science and Engineering Nanyang Technological University639798Singapore Zhejiang Engineering Research Center for Tissue Repair Materials Wenzhou InstituteUniversity of Chinese Academy of SciencesWenzhouZhejiang 325000PR China Oujiang Laboratory(Zhejiang Lab for Regenerative Medicine Vision and Brain Health)WenzhouZhejiang 325000PR China

As a hallmark of skin aging,senescent human dermal fibroblasts(HDFs)are known to lose the ability to divide.However,they can still interact with their cellular environment and the surrounding matrix.As the skin ages,the progressive slowing down of HDFs function decreases the skin’s structural integrity,which is more serious than if there is the dermal collagen matrix eroded.This leads to matters of the unbalanced barrier under the skin,skin fragility,inadequate wound healing,as well as other cosmetic issues.It is also well documented that skin aging comes with significant stiffness increases.Therefore,understanding the interactions between HDFs and the surrounding microenvironments during senescence may provide insights into skin aging.Here we aim to inves-tigate matrix stiffness’effect on HDF senescence and elucidate possible mechanisms that make HDFs senescent.In our experiments,HDFs were cultivated on Polydimethylsiloxane(PDMS)with various stiffnesses and exposed to UV light to trigger senescence.Results show that HDFs are significantly affected by senescence when cultured on a matrix with stiffness.However,the cells are not significantly affected when cultured on a low stiffness matrix.The following characterization revealed cells cultured on stiffsubstrates under UV exposure had stimu-lated the nucleus factor kappa-B(NF-κB)activation.In contrast,cells on a matrix of softness only displayed low activation of NF-κB.NF-κB activity suppression with ammonium pyrrolidine dithiocarbamate(PDTC)decreases UV-induced HDFs senescence on stiffsubstrates.Taken together,we demonstrated that soft matrix defends HDFs against ultraviolet-induced senescence by inhibiting the activation of NF-κB.

关键词： Human dermal fibroblasts Matrix stiffness senescence NF-κB

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Ganoderma atrum polysaccharide relieves mitochondrial dysfunction to alleviate hydrogen peroxide-induced senescence via activating autophagy

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Journal of Future Foods 2022年第3期2卷 241-252页

作者： Mi Guo Ke Zhang Duoduo Zhang Yujia Zhou Linyuan Liu Yu Wu Xingtao Zhou Shaoping Nie State Key Laboratory of Food Science and Technology China-Canada Joint Laboratory of Food Science and Technology(Nanchang)Key Laboratory of Bioactive Polysaccharides of Jiangxi ProvinceNanchang UniversityNanchang 330047China

Polysaccharides from genus Ganoderma have prominent anti-aging effect,but their mechanisms are incompletely clarified.In our previous experiments,Ganoderma atrum polysaccharide(PSG)was exhibited to significantly alleviate senescence and DNA damage of A375 cells.To investigate its underlying mechanism,we conducted RNA-Seq analysis and found that PSG upregulated autophagy and mitochondria pathways compared to the model group.Further experiments showed that PSG relieved mitochondrial dysfunction via inhibiting the accumulation of reactive oxygen species(ROS)and loss of the mitochondrial membrane potential(MMP).Meanwhile,PSG activated autophagy and enhanced lysosomal function through transcription factor EB(TFEB).Interestingly,the pretreatment of autophagy inhibitors bafilomycin A1(Baf A1)reversed the ROS decline induced by PSG,which subsequently increased cellular senescence of A375.In addition,PSG had a similar anti-aging effect on normal fibroblast WI-38.Taken together,PSG might reduce ROS levels through activating autophagy,which in turn suppressed mitochondrial dysfunction and cellular senescence.

关键词： Ganoderma atrum polysaccharide senescence Reactive oxygen species Autophagy Mitochondrial dysfunction

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senescence-Inducible Expression of Isopentenyl Transferase Extends Leaf Life,Increases Drought Stress Resistance and Alters Cytokinin Metabolism in Cassava

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Journal of Integrative Plant Biology 2010年第7期52卷 653-669页

作者： Peng Zhang Wen-Quan Wang Gen-Liang Zhang Miroslav Kaminek Petre Dobrev Jia Xu Wilhelm Gruissem Shanghai Center for Cassava Biotechnology National Laboratory of Plant Molecular Genetics Institute of Plant Physiology & Ecology Shanghai Institutes for Biological Sciences the Chinese Academy of Sciences Shanghai 200032 China Department of Biology Plant Biotechnology ETH Zurich Universitatstrasse 2 8092 Zurich Switzerland Institute of Tropical Biosciences and Biotechnology Chinese Academy of Tropical Agricultural Science Haikou 571101 China Institute of Experimental Botany Academy of Sciences of the Czech Republic Rozvojova 263 CZ-165 02 Prague 6 Czech Republic Key Laboratory of Synthetic Biology Institute of Plant Physiology & Ecology Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai 200032 China

Cassava （Manihot esculenta Crantz） sheds its leaves during growth, especially within the tropical dry season. With the production of SAG12-1PT transgenic cassava we want to test the level of leaf retention and altered cytokinin metabolism of transgenic plants via the autoregulatory senescence inhibition system. After confirmation of transgene expression by molecular analysis and phenotype examination in greenhouse plants, two transgenic plant lines, 529-28 and 529-48, were chosen for further investigation. Detached mature leaves of 529-28 plants retained high levels of chlorophyll compared with wild-type leaves after dark-induced senescence treatment. Line 529-28 showed significant drought tolerance as indicated by stay-green capacity after drought stress treatment. Field experiments proved that leaf senescence syndrome was significantly delayed in 529-28 plants in comparison with wild-type and 529-48 plants. Physiological and agronomical characterizations of these plants also revealed that the induced expression of IPT had effects on photosynthesis, sugar allocation and nitrogen partitioning. Importantly, the 529-28 plants accumulated a high level of trans-zeatin-type cytokinins particularly of corresponding storage O-glucosides to maintain cytokinin homeostasis. Our study proves the feasibility of prolonging the leaf life of woody cassava and also sheds light on the control of cytokinin homeostasis in cassava leaves.

关键词： Sheds Transgenic plants Cassava Leaves Cytokinins Transgenics Homeostasis Drought senescence Plants

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senescence in chronic wounds and potential targeted therapies

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Burns & Trauma 2022年第1期10卷 742-756页

作者： Xuerong Wei Minxiong Li Zijun Zheng Jun Ma Yanbin Gao Lianglong Chen Yujie Peng Shengxiang Yu Lei Yang Department of Burns Nanfang HospitalSouthern Medical UniversityJingxi StreetBaiyun DistrictGuangzhou510515China Department of Plastic and Reconstructive Surgery Shanghai Ninth People’s HospitalShanghai JiaoTong University School of Medicine639 Zhizaoju Road200011ShanghaiChina

Chronic wounds(e.***.diabetic wounds,pressure wounds,vascular ulcers,etc.)do not usually heal in a timely and orderly manner but rather last for years and may lead to irreversible adverse events,resulting in a substantial financial burden for patients and society.Recently,a large amount of evidence has proven that cellular senescence has a crucial influence on chronic nonhealing wounds.As a defensive mechanism,cell senescence is a manner of cell-cycle arrest with increased secretory phenotype to resist death,preventing cells from stress-induced damage in cancer and noncancer diseases.A growing amount of research has advanced the perception of cell senescence in various chronic wounds and focuses on pathological and physiological processes and therapies targeting senescent cells.However,previous reviews have failed to sum up novel understandings of senescence in chronic wounds and emerging strategies targeting senescence.Herein,we discuss the characteristics and mechanisms of cellular senescence and the link between senescence and chronic wounds as well as some novel antisenescence strategies targeting other diseases that may be applied for chronic wounds.

关键词： Chronic wounds senescence Senolytics Targeted therapies Diabetic wound Pressure wound Vascular ulcer

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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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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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Characterization and mapping of a novel mutant sms1 (senescence and male sterility 1) in rice

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Journal of Genetics and Genomics 2010年第1期37卷 47-55页

作者： Wenyi Yan Shenghai Ye Qingsheng Jin Longjun Zeng Yu Peng Dawei Yan Weibing Yang Donglei Yang Zuhua He Yanjun Dong Xiaoming Zhang College of Life and Environment Sciences Shanghai Normal UniversityShanghai 200234China Institute of Crop and Nuclear Technology Utilization Zhejiang Academy of Agricultural SciencesHangzhou 310021China Institute of Plant Physiology & Ecology Shanghai Institutes for Biological Sciences Chinese Academy of SciencesShanghai 200032China

Plant senescence plays diverse important roles in development and environmental responses.However,the molecular basis of plant senescence is remained largely unknown.A rice spontaneous mutant with the character of early senescence and male sterility （sms） was found in the breeding line NT10-748.In order to identify the gene SMS1 and the underlying mechanism,we preliminarily analyzed physiological and biochemical phenotypes of the mutant.The mutant contained lower chlorophyll content compared with the wild type control and was severe male sterile with lower pollen viability.Genetic analysis showed that the mutant was controlled by a single recessive gene.By the map-based cloning approach,we fine-mapped SMS1 to a 67 kb region between the markers Z3-4 and Z1-1 on chromosome 8 using 1,074 F2 recessive plants derived from the cross between the mutant sms1 （japonica） × Zhenshan 97 （indica）,where no known gene involved in senescence or male sterility has been identified.Therefore the SMS1 gene will be a novel gene that regulates the two developmental processes.The further cloning and functional analysis of the SMS1 gene is under way.

关键词： senescence male sterility rice molecular marker gene mapping

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TaSCL14,a Novel Wheat(Triticum aestivum L.)GRAS Gene,Regulates Plant Growth,Photosynthesis,Tolerance to Photooxidative Stress,and senescence

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Journal of Genetics and Genomics 2015年第1期42卷 21-32页

作者： Kunmei Chen Hongwei Li Yaofeng Chen Qi Zheng Bin Li Zhensheng Li College of Agronomy Northwest A&F University State Key Laboratory of Plant Cell and Chromosome Engineering Institute of Genetics and Developmental BiologyChinese Academy of Sciences

Rates of photosynthesis, tolerance to photooxidative stress, and senescence are all important physiological factors that affect plant development and thus agricultural productivity. GRAS proteins play essential roles in plant growth and development as well as in plant responses to biotic and abiotic stresses. So far few GRAS genes in wheat （Triticum aestivum L.） have been characterized. A previous transcriptome analysis indicated that the expression of a GRAS gene （TaSCL14） was induced by high-light stress in Xiaoyan 54 （XY54）, a common wheat cultivar with strong tolerance to high-light stress. In this study, TaSCL14 gene was isolated from XY54 and mapped on chromosome 4A. TaSCL14 was expressed in various wheat organs, with high levels in stems and roots. Our results confirmed that TaSCL14 expression was indeed responsive to high-light stress. Barley stripe mosaic virus （BSMV）-based virus-induced gene silencing （VIGS） of TaSCL14 in wheat was performed to help characterize its potential functions. Silencing of TaSCL14 resulted in inhibited plant growth, decreased photosynthetic capacity, and reduced tolerance to photooxidative stress. In addition, silencing of TaSCL14 in wheat promoted leaf senescence induced by darkness. These results suggest that TaSCL14 may act as a multifunctional regulator involved in plant growth, photosynthesis, tolerance to photooxidative stress, and senescence.

关键词： Triticum aestivum L. TaSCL14 Photosynthesis Photooxidative resistance senescence BSMV--VIGS

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

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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 China 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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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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