Chondrocyte senescence is a critical pathological hallmark of osteoarthritis(OA).Aberrant mechanical stress is considered a pivotal determinant in chondrocyte aging;however,the precise underlying mechanism remains elu...Chondrocyte senescence is a critical pathological hallmark of osteoarthritis(OA).Aberrant mechanical stress is considered a pivotal determinant in chondrocyte aging;however,the precise underlying mechanism remains elusive.Our findings demonstrate that SPI1 plays a significant role in counteracting chondrocyte senescence and inhibiting OA progression.SPI1 binds to the PERK promoter,thereby promoting its transcriptional activity.Importantly,PERK,rather than GCN2,facilitates eIF2αphosphorylation,activating the mitochondrial unfolded protein response(UPRmt)and impeding chondrocyte senescence.Deficiency of SPI1 in mechanical overload-induced mice leads to diminished UPRmt activation and accelerated OA progression.Intra-articular injection of adenovirus vectors overexpressing SPI1 and PERK effectively mitigates cartilage degeneration.In summary,our study elucidates the crucial regulatory role of SPI1 in the pathogenesis of chondrocyte senescence by activating UPRmt signaling through PERK,which may present a novel therapeutic target for treating OA.展开更多
Cellular senescence and its senescence-associated secretory phenotype(SASP)represent a pivotal role in the development of skeletal diseases.Targeted elimination or rejuvenation of senescent cells has shown potential a...Cellular senescence and its senescence-associated secretory phenotype(SASP)represent a pivotal role in the development of skeletal diseases.Targeted elimination or rejuvenation of senescent cells has shown potential as a therapeutic strategy to reverse age-related skeletal senescence and promote bone regeneration.Meanwhile,other age-related mechanisms,involving altered cellular functions,impaired intercellular crosstalk,disturbed tissue microenvironment,and decreased regenerative capacity,synergistically contribute to the pathogenesis.In this review,we outline the cellular senescence and other age-related mechanisms in developing skeletal diseases,including osteoporosis,intervertebral disc degeneration,osteoarthritis,rheumatoid arthritis,bone tumors and ankylosing spondylitis,with the aim of comprehensively understanding their detrimental effects on the aged skeleton and screening the potential targets for anti-aging therapy within the skeletal system.展开更多
Aging is considered the main risk factor for the development of several diseases,including the leading neurodegenerative disorders.While the cellular features of aging are complex and multifaceted,neuronal senescence ...Aging is considered the main risk factor for the development of several diseases,including the leading neurodegenerative disorders.While the cellular features of aging are complex and multifaceted,neuronal senescence has emerged as a major contributor and driver of this process in the mammalian cell.Cellular senescence is a programmed response to stress and irreparable damage,which drives the cell into an apoptosis-resistant,non-proliferative state.Senescent cells can also deleteriously affect neighboring,non-senescent cells.Senescence is a complex and multifaceted process associated with a wide range of cellular events,including the secretion of pro-inflammatory molecules and the arrest of the cell cycle.展开更多
Intervertebral disc degeneration(IDD)is a progressive and dynamic process in which the senescence-associated secretory phenotype(SASP)of nucleus pulposus cells(NPC)plays a significant role.While impaired chaperone-med...Intervertebral disc degeneration(IDD)is a progressive and dynamic process in which the senescence-associated secretory phenotype(SASP)of nucleus pulposus cells(NPC)plays a significant role.While impaired chaperone-mediated autophagy(CMA)has been associated with inflammation and cellular senescence,its specific involvement in the self-perpetuating feedback loop of NPC senescence remains poorly understood.Through LAMP2A knockout in NPC,we identified a significant upregulation of DYRK1A,a core mediator of premature senescence in Down syndrome.Subsequent validation established DYRK1A as the critical driver of premature senescence in CMA-deficient NPC.Combinatorial transcription factor analysis revealed that under IL1B stimulation or CMA inhibition,elevated DYRK1A promoted FOXC1 phosphorylation and nuclear translocation,initiating transcriptional activation of cell cycle arrest.Intriguingly,CMA impairment concurrently enhanced glutamine metabolic flux in senescent NPC,thereby augmenting their survival fitness.Transcriptomic profiling demonstrated that CMA reactivation in senescent NPC facilitated fate transition from senescence to apoptosis,mediated by decreased glutamine flux via GLUL degradation.Therefore,CMA exerts protective effects against IDD by maintaining equilibrium between premature senescence and senolysis.This study elucidates CMA’s regulatory role in SASP-mediated senescence amplification circuits,providing novel therapeutic insights for IDD and other age-related pathologies.展开更多
Diabetic kidney disease(DKD)has emerged as one of the leading causes of chronic kidney disease and end-stage renal disease worldwide.In the progression of DKD,renal tubular injury plays a pivotal role,with stress-indu...Diabetic kidney disease(DKD)has emerged as one of the leading causes of chronic kidney disease and end-stage renal disease worldwide.In the progression of DKD,renal tubular injury plays a pivotal role,with stress-induced senescence of renal tubular epithelial cells(RTECs)being a critical cellular event contributing to tubular damage in DKD.Recent studies have revealed that multiple mechanisms,including oxidative stress,mitochondrial autophagy,endoplasmic reticulum stress,and epigenetic modifications,can induce stress-induced senescence in RTECs,thereby driving the progression of DKD.In recent years,research has demonstrated that traditional Chinese medicine(TCM)can regulate these mechanisms through multiple targets and key pathways,inhibiting stress-induced senescence in RTECs and ameliorating the progression of DKD.TCM has been widely applied in clinical practice with proven efficacy.This article systematically summarizes the concept of cellular senescence,delves into the relationship between stress-induced senescence of RTECs and DKD,analyzes the mechanisms underlying the formation of stress-induced senescence in RTECs within the context of DKD,and reviews the research progress of TCM in anti-senescence treatment for DKD.The aim is to provide a reference for future research and the development of novel therapeutic strategies.展开更多
Stem cells play a crucial role in maintaining tissue regenerative capacity and homeostasis.However,mechanisms associated with stem cell senescence require further investigation.In this study,we conducted a proteomic a...Stem cells play a crucial role in maintaining tissue regenerative capacity and homeostasis.However,mechanisms associated with stem cell senescence require further investigation.In this study,we conducted a proteomic analysis of human dental pulp stem cells(HDPSCs)obtained from individuals of various ages.Our findings showed that the expression of NUP62 was decreased in aged HDPSCs.We discovered that NUP62 alleviated senescence-associated phenotypes and enhanced differentiation potential both in vitro and in vivo.Conversely,the knocking down of NUP62 expression aggravated the senescence-associated phenotypes and impaired the proliferation and migration capacity of HDPSCs.Through RNA-sequence and decoding the epigenomic landscapes remodeled induced by NUP62 overexpression,we found that NUP62 helps alleviate senescence in HDPSCs by enhancing the nuclear transport of the transcription factor E2F1.This,in turn,stimulates the transcription of the epigenetic enzyme NSD2.Finally,the overexpression of NUP62 influences the H3K36me2 and H3K36me3 modifications of anti-aging genes(HMGA1,HMGA2,and SIRT6).Our results demonstrated that NUP62 regulates the fate of HDPSCs via NSD2-dependent epigenetic reprogramming.展开更多
To determine the effects of preharvest arginine spraying on the nutritional level of broccoli and the mechanism of action of arginine in improving the storage quality of broccoli,arginine spraying(5 mmol/L)was conduct...To determine the effects of preharvest arginine spraying on the nutritional level of broccoli and the mechanism of action of arginine in improving the storage quality of broccoli,arginine spraying(5 mmol/L)was conducted at 0,1,3,and 5 days before harvest.The appearance,respiration rate,mass-loss rate,electrolyte leakage,glucosinolate,ascorbic acid,total phenol,total flavonoid,total sugar and sucrose contents,and sucrose phosphate synthase(SPS),invertase(INV),sucrose synthase synthesis(SSS)and cleavage(SSC)activities of broccoli samples were observed after 0,2,4,6,8,and 10 days of storage.The results showed that spraying arginine at 5 days preharvest(5-ARG)helped to inhibit broccoli respiration during storage,delay electrolyte leakage,and maintain broccoli color.Furthermore,during the growth stage,total sugar accumulation was higher in the 5-ARG group.In addition,during the storage period,sucrose synthesis was accelerated,while sucrose cleavage was inhibited,resulting in more sucrose retention in postharvest broccoli.In conclusion,5-ARG resulted in the accumulation of more nutrients during the growth process and effectively delayed the quality decline during storage,thereby prolonging the shelf life of broccoli.Therefore,this study provides a theoretical basis for improving postharvest storage characteristics of broccoli through preharvest treatments.展开更多
Objective The nucleolar protein PES1(Pescadillo homolog 1)plays critical roles in ribosome biogenesis and cell cycle regulation,yet its involvement in cellular senescence remains poorly understood.This study aimed to ...Objective The nucleolar protein PES1(Pescadillo homolog 1)plays critical roles in ribosome biogenesis and cell cycle regulation,yet its involvement in cellular senescence remains poorly understood.This study aimed to comprehensively investigate the functional consequences of PES1 suppression in cellular senescence and elucidate the molecular mechanisms underlying its regulatory role.Methods Initially,we assessed PES1 expression patterns in two distinct senescence models:replicative senescent mouse embryonic fibroblasts(MEFs)and doxorubicin-induced senescent human hepatocellular carcinoma HepG2 cells.Subsequently,PES1 expression was specifically downregulated using siRNA-mediated knockdown in these cell lines as well as additional relevant cell types.Cellular proliferation and senescence were assessed by EdU incorporation and SA-β-gal staining assays,respectively.The expression of senescence-associated proteins(p53,p21,and Rb)and SASP factors(IL-6,IL-1β,and IL-8)were analyzed by Western blot or qPCR.Furthermore,Northern blot and immunofluorescence were employed to evaluate pre-rRNA processing and nucleolar morphology.Results PES1 expression was significantly downregulated in senescent MEFs and HepG2 cells.PES1 knockdown resulted in decreased EdU-positive cells and increased SA-β-gal-positive cells,indicating proliferation inhibition and senescence induction.Mechanistically,PES1 suppression activated the p53-p21 pathway without affecting Rb expression,while upregulating IL-6,IL-1β,and IL-8 production.Notably,PES1 depletion impaired pre-rRNA maturation and induced nucleolar stress,as evidenced by aberrant nucleolar morphology.Conclusion Our findings demonstrate that PES1 deficiency triggers nucleolar stress and promotes p53-dependent(but Rb-independent)cellular senescence,highlighting its crucial role in maintaining nucleolar homeostasis and regulating senescence-associated pathways.展开更多
Intervertebral disc degeneration is a major risk factor contributing to chronic low back and neck pain.While the etiological factors for disc degeneration vary,age is still one of the most important risk factors.Recen...Intervertebral disc degeneration is a major risk factor contributing to chronic low back and neck pain.While the etiological factors for disc degeneration vary,age is still one of the most important risk factors.Recent studies have shown the promising role of SIRT6 in mammalian aging and skeletal tissue health,however its role in the intervertebral disc health remains unexplored.We investigated the contribution of SIRT6 to disc health by studying the age-dependent spinal phenotype of mice with conditional deletion of Sirt6 in the disc(AcanCreERT2;Sirt6fl/fl).Histological studies showed a degenerative phenotype in knockout mice compared to Sirt6fl/fl control mice at 12 months,which became pronounced at 24 months.RNA-Seq analysis of NP and AF tissues,in vitro quantitative histone analysis,and RNA-seq with ATAC-seq multiomic studies revealed that SIRT6-loss resulted in changes in acetylation and methylation status of specific Histone 3 lysine residues and affected DNA accessibility and transcriptomic landscape.A decrease in autophagy and an increase in DNA damage were also noted in Sirt6-deficient cells.Further mechanistic insights revealed that loss of SIRT6 increased senescence and SASP burden in the disc characterized by increased p21,p19,γH2AX,IL-6,IL-1β,and TGF-βabundance.Taken together,our study highlights the contribution of SIRT6 in modulating DNA damage,autophagy,and cell senescence and its importance in maintaining disc health during aging,thereby underscoring it as a potential therapeutic target to treat intervertebral disc degeneration.展开更多
Non-destructive time-series assessment of chlorophyll content in flag-leaf(FLC)accurately mimics the senescence rate and the identification of genetic loci associated with senescence provides valuable knowledge to imp...Non-destructive time-series assessment of chlorophyll content in flag-leaf(FLC)accurately mimics the senescence rate and the identification of genetic loci associated with senescence provides valuable knowledge to improve yield stability under stressed environments.In this study,we employed both unmanned aerial vehicles(UAVs)equipped with red–green–blue(RGB)camera and ground-based SPAD-502 instrument to conduct temporal phenotyping of senescence.A total of 262 recombinant inbred lines derived from the cross of Zhongmai 578/Jimai 22 were evaluated for senescence-related traits across three environments,spanning from heading to 35 d post-anthesis.The manual senescence rate(MSR)was quantified using the FLC and the active accumulated temperature,and UAV derived vegetation index were utilized to assess the stay-green rate(USG)facilitating the identification of senescent and stay-green lines.Results indicated that higher senescence rates significantly impacted grain yield,primarily by influencing thousand-kernel weight,and plant height.Quantitative trait loci(QTL)mapping for FLC,USG,and MSR using the 50K SNP array identified 38 stable loci associated with RGB-based vegetation indices and senescence-related traits:among which 19 loci related to senescence traits from UAV and FLC were consistently detected across at least two growth stages,with nine loci likely representing novel QTL.This study highlights the potential of UAV-based high-throughput phenotyping and phenology in identifying critical loci associated with senescence rates in wheat,validating the relationship between senescence rates and yield-related traits in wheat,offering valuable opportunities for gene discovery and significant applications in breeding programs.展开更多
Developing and identifying effective medications and targets for treating hepatic fibrosis is an urgent priority.Our previous research demonstrated the efficacy of artesunate(ART)in alleviating liver fibrosis by elimi...Developing and identifying effective medications and targets for treating hepatic fibrosis is an urgent priority.Our previous research demonstrated the efficacy of artesunate(ART)in alleviating liver fibrosis by eliminating activated hepatic stellate cells(HSCs).However,the underlying mechanism remains unclear despite these findings.Notably,endocytic adaptor protein(NUMB)has significant implications for treating hepatic diseases,but current research primarily focuses on liver regeneration and hepatocellular carcinoma.The precise function of NUMB in liver fibrosis,particularly its ability to regulate HSCs,requires further investigation.This study aims to elucidate the role of NUMB in the anti-hepatic fibrosis action of ART in HSCs.We observed that the expression level of NUMB significantly decreased in activated HSCs compared to quiescent HSCs,exhibiting a negative correlation with the progression of liver fibrosis.Additionally,ART induced senescence in activated HSCs through the NUMB/P53 tumor suppressor(P53)axis.We identified NUMB as a crucial regulator of senescence in activated HSCs and as a mediator of ART in determining cell fate.This research examines the specific target of ART in eliminating activated HSCs,providing both theoretical and experimental evidence for the treatment of liver fibrosis.展开更多
Drought is one of the important stress factors affecting the growth and development processes of wheat in China's arid zones, which severely limits the yield. This study examined the impact of deficit irrigation o...Drought is one of the important stress factors affecting the growth and development processes of wheat in China's arid zones, which severely limits the yield. This study examined the impact of deficit irrigation on the flag leaf protection system and yield of drip-irrigated spring wheat during the growth stages in arid zones. In addition, this study aimed to determine the optimal water supply mode for efficient production under drip irrigation conditions and to provide technical support for water-saving and high-yield cultivation of drip-irrigated wheat. The experiment was conducted with a split plot design using the water-sensitive variety Xinchun 22(XC22) and the drought-tolerant variety Xinchun 6(XC6) as the main plots, while a fully irrigated control(CK, 75–80% FC, where FC is field water holding capacity), mild deficit(T1, 60–65% FC) and moderate deficit(T2, 45–50% FC) at the tillering stage, and mild deficit(J1, 60–65% FC) and moderate deficit(J2, 45–50% FC) at the jointing stage were used as the subplots. Systematic studies were conducted on the regulatory effects of deficit irrigation during the tillering and jointing stages on protective substances, membrane lipid metabolism, endogenous hormones in the flag leaf, and yield of spring wheat. Compared with treatments T2 and J2, treatments T1 and J1 were beneficial for increasing the activities of superoxide dismutase(SOD), peroxidase(POD), and catalase(CAT), the levels of proline(Pro), indole-3-acetic acid(IAA), and zeatin riboside(ZR), and the ratios IAA/abscisic acid(ABA), ZR/ABA, IAA/ZR, and(IAA+ZR)/ABA, while reducing the levels of hydrogen peroxide(H2O2), superoxide anion radicals(O2–·), malondialdehyde(MDA), phosphatidic acid(PA), free fatty acids(FFA), ABA, phospholipase D(PLD), and lipoxygenase(LOX), alleviating flag leaf senescence, and increasing yield. Under treatment T1, the SOD, POD, CAT, and Pro levels of flag leaves in XC6 were 11.14, 8.08, 12.98, and 3.66% higher than those of treatment CK, and under treatment J1, they were 6.43, 4.49, 7.36, and 2.50% higher than those of treatment CK. Under treatment T1 in XC6, the IAA, ZR level of the flag leaf, spike number, grains per spike, 1,000-grain weight and yield were 10.50, 5.79, 3.10, 8.84, 3.78, and 10.52% higher than those of treatment CK, and under treatment J1, they were 5.36, 3.94, 2.40, 3.72, 1.37, and 4.46% higher than those of treatment CK. Compared with XC22, XC6 was more conducive to the improvement of flag leaf protective substances, IAA, ZR, dry matter weight, yield components and yield. The correlation analysis showed significant positive correlations between IAA and ZR with SOD, POD, CAT, proline, and yield. IAA and ZR promoted the enhancement of protective enzyme activities, thereby clearing reactive oxygen species to cope with the oxidative stress caused by drought and achieve the effect of delaying senescence. Principal component analysis showed that yield components and dry matter weight, had direct effects on yield. Mild deficiency during the tillering stage without water stress in other stages could effectively optimize yield components, not only achieving high yield while increasing protective substances, but also reducing the reactive oxygen species content. This strategy can be recommended as a water-saving and high-yield production mode for drip irrigation of spring wheat in Xinjiang, China.展开更多
Senescence,a crucial developmental process in the life cycle of plants,involves programmed destruction of cellular components of leaves.The onset of senescence is synchronized with other developmental processes for su...Senescence,a crucial developmental process in the life cycle of plants,involves programmed destruction of cellular components of leaves.The onset of senescence is synchronized with other developmental processes for successful reproduction since senescence eventually leads to cell death.Arabinosyltransferase FASCIATED AND BRANCHED 2(FAB2)is known to control meristem proliferation.Here,we show that FAB2 could inhibit premature leaf senescence in tomato plants.Both chemically mutagenized and CRISPR-generated fab2 mutants exhibited excessively accelerated senescence,which resulted in sterility.Transcriptome analysis revealed that FAB2 extended leaf longevity by suppressing transcription of genes highly expressed in mature leaves.Transcription of FAB2 was increased in younger leaves,potentially inhibiting premature leaf senescence.The precocious senescence of fab2 mutants was in contrast to fasciated inflorescence(fin)mutants,which carried mutations in a hydroxyproline O-arabinosyltransferase gene,leading to meristem overproliferation.Our observations indicate that complex genetic hierarchy in the cascade of tomato arabinosyltransferases could control different aspects of developmental processes such as stem cell proliferation and senescence.展开更多
Premature senescence in Bacillus thuringiensis(Bt)cotton has emerged as a significant challenge to the formation and realization of fiber yield and quality since its commercialization in 1997.Initially,premature senes...Premature senescence in Bacillus thuringiensis(Bt)cotton has emerged as a significant challenge to the formation and realization of fiber yield and quality since its commercialization in 1997.Initially,premature senescence was thought to be an inherent trait associated with the Bt gene.However,subsequent research and practice have demonstrated that it is not directly linked to the Bt gene but rather results from a physiological imbalance between the sink and source,as well as between the root and shoot in Bt cotton.This short review provides an overview of the causes,mechanisms,and control measures for premature senescence in Bt cotton.It offers valuable insights for future research and the sustainable application of transgenic crops.展开更多
Background:Breast cancer ranks as the most common cancer in women globally,presenting major challenges primarily due to the emergence of resistance to existing therapies and the adverse side effects linked with these ...Background:Breast cancer ranks as the most common cancer in women globally,presenting major challenges primarily due to the emergence of resistance to existing therapies and the adverse side effects linked with these treatments.Natural compounds,such as quercetin,a flavonoid found in Artemisia annua,have gained attention for their multi-targeted therapeutic potential.This research aims to investigate the pharmacological effects of quercetin in inducing cellular senescence in breast cancer cells utilizing network pharmacology.Methods:Initially,the active compounds of Artemisia annua were identified through the Traditional Chinese Medicine Systems Pharmacology database.The breast cancer-related genes were gathered from various databases.The intersection between the genes associated with breast cancer and the targets of active pharmaceutical ingredients was analyzed.Additionally,the regulatory network of active ingredients and their targets was researched.Further,protein-protein interaction was acquired from STRING database and core targets were analyzed.The analyses of Gene Ontology functional enrichment and Kyoto Encyclopedia of Genes and Genomes pathway enrichment were conducted utilizing R programming language.Results:In Artemisia annua,18 active compounds were identified along with their associated target proteins,among which quercetin exhibiting the highest number of target proteins.2897 disease-related genes were discovered,and 145 drug-disease intersection targets were selected.The analysis focused on the impact of quercetin on cellular senescence,informed by core target analysis and enrichment results.Molecular docking studies demonstrated the stable binding of quercetin to cyclin-dependent kinase 2(CDK2),which was chosen for experimental validation.Conclusion:The research highlights the promising therapeutic efficacy of quercetin on breast cancer by the induction of cellular senescence,offering valuable biological insights and establishing a foundation for future research.展开更多
Background:Osteoarthritis(OA)is a long-term degenerative joint disease worsen-ing over time.Aging and chondrocyte senescence contribute to OA progression.MicroRNAs have been confirmed to regulate different cellular pr...Background:Osteoarthritis(OA)is a long-term degenerative joint disease worsen-ing over time.Aging and chondrocyte senescence contribute to OA progression.MicroRNAs have been confirmed to regulate different cellular processes.They con-tribute to OA pathology and may help to identify novel biomarkers and therapies for OA.Methods:This study used bioinformatics and experimental investigations to analyze and validate differentially expressed miRNAs in OA that might affect chondrocyte apoptosis and senescence.Results:miR-6779 was found to be significantly down-regulated in OA.Seventy-six of the predicted and miR-6779 targeted genes and the OA-associated disease genes overlapped,and these were enriched in cell proliferation,cell apoptosis,and cell cycle.miR-6779 overexpression remarkably attenuated IL-1βeffects on chon-drocytes by reducing MMP3 and MMP13 levels,promoting cell apoptosis,suppress-ing cell senescence,and increasing caspase-3,caspase-9 and reducing P16 and P21 levels.miR-6779 targeted inhibition of X-linked inhibitor of apoptosis protein(XIAP)expression.XIAP knockdown partially improved IL-1β-induced chondrocyte senes-cence and dysfunction.Lastly,when co-transfected with a miR-6779 agomir,the XIAP overexpression vector partially attenuated the effects of miR-6779 overexpression on chondrocytes;miR-6779 improved IL-1β-induced senescence and dysfunction in chondrocytes through targeting XIAP.Conclusion:miR-6779 is down-regulated,and XIAP is up-regulated in OA cartilage and IL-1β-treated chondrocytes.miR-6779 inhibits XIAP expression,thereby promot-ing senescent chondrocyte cell apoptosis and reducing chondrocyte senescence and ECM loss through XIAP.展开更多
Intercropping has been widely used in arid and semi-arid regions because of its high yield,stable productivity,and efficient utilization of resources.However,in recent years,the high yield of traditional intercropping...Intercropping has been widely used in arid and semi-arid regions because of its high yield,stable productivity,and efficient utilization of resources.However,in recent years,the high yield of traditional intercropping is mainly attributed to the large amount of purchased resources such as water and fertilizer,plastic film,and mechanical power.These lead to a decline in cultivated land quality and exacerbate intercrops'premature root and canopy senescence.So,the application of traditional intercropping faces major challenges in crop production.This paper analyzes the manifestations,occurrence mechanisms,and agronomic regulatory pathways of crop senescence.The physiological and ecological characteristics of intercropping to delay root and canopy senescence of crops are reviewed in this paper.The main agronomic regulatory pathways of intercropping to delay root and canopy senescence of crops are based on above-and blow-ground interactions,including collocation of crop varieties,spatial arrangement,water and fertilizer management,and tillage and mulch practices.Future research fields of intercropping to delay root and canopy senescence should focus on the aspects of selecting and breeding special varieties,application of molecular biology techniques,and developing or applying models to predict and evaluate the root and canopy senescence process of intercrops.Comprehensive analysis and evaluation of different research results could provide a basis for enhancing intercropping delay root and canopy senescence through adopting innovative technologies for regulating the physio-ecological characteristics of intercrops.This would support developing and adopting high-yield,efficient,and sustainable intercropping systems in arid and semi-arid areas with high population density,limited land,and abundant light and heat resources.展开更多
Objective:Neuroblastoma(NB)is frequently associated with high-risk pediatric cases that demonstrate limited response to cisplatin,contributing to a poor prognosis.Recent studies have explored the role of tumor cell se...Objective:Neuroblastoma(NB)is frequently associated with high-risk pediatric cases that demonstrate limited response to cisplatin,contributing to a poor prognosis.Recent studies have explored the role of tumor cell senescence in increasing sensitivity to this chemotherapy agent.This study aims to identify genes related to cell senescence in children diagnosed with NB,evaluate their influence on cisplatin sensitivity,and investigate potential strategies to enhance the efficacy of chemotherapy.Methods:Gene expression profiles and clinical data were obtained for 498 NB patients from the GEO database(GSE49710).The study focused on identifying genes that were differentially expressed between stage IV and other stages,particularly those linked to cell senescence and cisplatin resistance.To analyze the prognostic significance of these differentially expressed genes,we employed LASSO regression and multivariate Cox proportional hazards models.Transcriptomic and proteomic analyses of 15 NB specimens revealed a significant correlation between Flap endonuclease-1(FEN1)expression levels and both cellular senescence and sensitivity to cisplatin.We quantified FEN1 expression and cisplatin IC50 values in four different NB cell lines.The influence of FEN1 knockdown and overexpression on NB cell proliferation,invasion,and migration was evaluated using cloning assays,transwell assays,and scratch assays.Furthermore,we utilized Western blotting to analyze senescenceassociated proteins p21 and proliferating cell nuclear antigen(PCNA),thereby evaluating the role of FEN1 in cellular senescence.The impact of FEN1 on cisplatin sensitivity was investigated via the CCK-8 cell counting assay.Additionally,we investigated how FEN1 inhibitors might impact NB cell proliferation and enhance the therapeutic efficacy of cisplatin treatment.Results:FEN1 was found to be highly expressed in stage IV NB and showed a strong association with cisplatin sensitivity,establishing it as a critical molecular marker linked to poor patient prognosis.Notably,elevated FEN1 expression correlated with reduced sensitivity to cisplatin,as evidenced by higher IC50 values.In the SH-SY5Y cell line,FEN1 knockdown led to significant reductions in cell proliferation,invasion,and migration,along with an increase inβ-galactosidase staining—indicative of senescence.This knockdown also resulted in elevated levels of the p21 protein and decreased expression of PCNA,concurrently lowering cisplatin IC50 values.Conversely,FEN1 overexpression in the SK-N-SH cell line resulted in enhanced cell proliferation,invasion,and migration.This overexpression was associated with reducedβ-galactosidase staining,decreased levels of p21,and increased expression of PCNA,ultimately resulting in higher cisplatin IC50 values.Importantly,FEN1 inhibitors alone significantly impeded NB cell proliferation,and their combination with cisplatin further amplified this inhibitory effect compared to cisplatin treatment alone.Conclusions:Bioinformatics and sequencing analyses indicate that the senescence-related gene FEN1 is significantly associated with cisplatin sensitivity and adverse prognosis in pediatric NB.FEN1 plays a pivotal role in regulating NB cell proliferation,invasion,and migration,thereby facilitating cancer progression.Furthermore,it influences cisplatin sensitivity through its effects on cellular senescence.FEN1 inhibitors demonstrate potential both as monotherapies and in conjunction with cisplatin,suggesting that targeting FEN1 may be represent a valuable strategy for improving outcomes in high-risk NB patients.展开更多
The postharvest senescence phase of table grapes comprises a series of biological processes.MicroRNAs(miRNAs)regulate downstream genes at the post-transcriptional level;however,whether miRNAs are involved in postharve...The postharvest senescence phase of table grapes comprises a series of biological processes.MicroRNAs(miRNAs)regulate downstream genes at the post-transcriptional level;however,whether miRNAs are involved in postharvest grape senescence remains unclear.We used small RNA sequencing to identify postharvest-related miRNAs in‘Red Globe'(Vitis vinifera)grapes harvested after 0,30,and 60 d of storage at 4℃(RG0,RG30,RG60).In total,42 known and 219 novel miRNA candidates were obtained.During fruit senescence,the expression of PC-3p-3343_1921,mi R2950,miR395k,miR2111,miR159c,miR169q,PC-5p-1112_4500,and miR167b changed signifcantly(P<0.05).Degradation sequencing identifed 218 targets associated with cell wall organization,tricarboxylic acid(TCA)cycling,pathogen defense,carbon metabolism,hormone signaling,the anthocyanin metabolism pathway,and energy regulation,of which ARF6,GRF3,TCP2,CP1,MYBA2,and WRKY72 were closely related to fruit senescence.We also verified that VIT_00s2146g00010,VIT_02s0012g01750,and VIT_03s0038g00160 with unknown functions are cleaved by senescence-related PC-5p-1112_4500 via the dual luciferase assay,and the transient transformation of grape berries showed that they regulate berry senescence.These results deepen our understanding of the role of mi RNAs in regulating grape berry senescence and prolonging the shelf life of horticultural products.Based on these results,we propose a new theoretical strategy for delaying the postharvest senescence of horticultural products by regulating the expression of key miRNAs(e.g.,PC-5p-1112_4500),thereby extending their shelf life.展开更多
Alzheimer’s disease(AD)is a neurodegenerative disease causing the most frequent form of dementia in old age.AD etiology is still uncertain and deposition of abnormal proteins in the brain along with chronic neuroinfl...Alzheimer’s disease(AD)is a neurodegenerative disease causing the most frequent form of dementia in old age.AD etiology is still uncertain and deposition of abnormal proteins in the brain along with chronic neuroinflammation have been suggested as pathogenic mechanisms of neuronal death.Infections by exogenous neurotropic virus,endogenous retrovirus reactivation,infections by other microbes,and air pollutants may either induce neurodegeneration or activate brain inflammation.Up to 8%of the human genome has a retroviral origin.These ancient retroviruses,also called human endogenous retroviruses,are associated with a clinical history of several neurodegenerative diseases.Under persistent stress,such as chronic infections and inflammation,neurons,and microglia cells may enter a state of division inactivation called cell senescence.Senescent cells are resistant to apoptosis and can release pro-inflammatory molecules promoting the functional decline of tissues and organs and also activate silent viruses.Infections andmutations induced by pollutants can lead to the expression of different endogenous retroviruses,which may contribute to several different diseases,including AD-associated neurodegeneration.Here I discuss that infection by exogenous pathogen,activation of endogenous retrovirus or retrotransposons and pollutants might induce neuronal senescence and cause persistent brain neurodegeneration.Therefore,cell senescence appears to be an emerging mechanism that might contribute to AD neurodegeneration.Finally,treatment of AD patients with senolytic drugs,e.g.,compounds able to kill senescent cells,might show a positive effect on AD progression.展开更多
基金supported by the Anhui Provincial Natural Science Foundation(Grant No.2308085MH250)the Natural Science Research Project of Anhui Educational Committee(Grant No.2023AH053327)the Scientific Research Fund Project of Anhui Medical University(2020xkj039).
文摘Chondrocyte senescence is a critical pathological hallmark of osteoarthritis(OA).Aberrant mechanical stress is considered a pivotal determinant in chondrocyte aging;however,the precise underlying mechanism remains elusive.Our findings demonstrate that SPI1 plays a significant role in counteracting chondrocyte senescence and inhibiting OA progression.SPI1 binds to the PERK promoter,thereby promoting its transcriptional activity.Importantly,PERK,rather than GCN2,facilitates eIF2αphosphorylation,activating the mitochondrial unfolded protein response(UPRmt)and impeding chondrocyte senescence.Deficiency of SPI1 in mechanical overload-induced mice leads to diminished UPRmt activation and accelerated OA progression.Intra-articular injection of adenovirus vectors overexpressing SPI1 and PERK effectively mitigates cartilage degeneration.In summary,our study elucidates the crucial regulatory role of SPI1 in the pathogenesis of chondrocyte senescence by activating UPRmt signaling through PERK,which may present a novel therapeutic target for treating OA.
基金supported by the National Natural Science Foundation of China(82172468,82372436)Outstanding Youth Fund of Jiangsu Province(BK2024047)+1 种基金China Postdoctoral Science Foundation(2023T160553)Postgraduate Research&Practice Innovation Program of Jiangsu Province(SJCX22-1819).
文摘Cellular senescence and its senescence-associated secretory phenotype(SASP)represent a pivotal role in the development of skeletal diseases.Targeted elimination or rejuvenation of senescent cells has shown potential as a therapeutic strategy to reverse age-related skeletal senescence and promote bone regeneration.Meanwhile,other age-related mechanisms,involving altered cellular functions,impaired intercellular crosstalk,disturbed tissue microenvironment,and decreased regenerative capacity,synergistically contribute to the pathogenesis.In this review,we outline the cellular senescence and other age-related mechanisms in developing skeletal diseases,including osteoporosis,intervertebral disc degeneration,osteoarthritis,rheumatoid arthritis,bone tumors and ankylosing spondylitis,with the aim of comprehensively understanding their detrimental effects on the aged skeleton and screening the potential targets for anti-aging therapy within the skeletal system.
文摘Aging is considered the main risk factor for the development of several diseases,including the leading neurodegenerative disorders.While the cellular features of aging are complex and multifaceted,neuronal senescence has emerged as a major contributor and driver of this process in the mammalian cell.Cellular senescence is a programmed response to stress and irreparable damage,which drives the cell into an apoptosis-resistant,non-proliferative state.Senescent cells can also deleteriously affect neighboring,non-senescent cells.Senescence is a complex and multifaceted process associated with a wide range of cellular events,including the secretion of pro-inflammatory molecules and the arrest of the cell cycle.
基金supported by the National Natural Science Foundation of China (NSFC) (No.82172497)
文摘Intervertebral disc degeneration(IDD)is a progressive and dynamic process in which the senescence-associated secretory phenotype(SASP)of nucleus pulposus cells(NPC)plays a significant role.While impaired chaperone-mediated autophagy(CMA)has been associated with inflammation and cellular senescence,its specific involvement in the self-perpetuating feedback loop of NPC senescence remains poorly understood.Through LAMP2A knockout in NPC,we identified a significant upregulation of DYRK1A,a core mediator of premature senescence in Down syndrome.Subsequent validation established DYRK1A as the critical driver of premature senescence in CMA-deficient NPC.Combinatorial transcription factor analysis revealed that under IL1B stimulation or CMA inhibition,elevated DYRK1A promoted FOXC1 phosphorylation and nuclear translocation,initiating transcriptional activation of cell cycle arrest.Intriguingly,CMA impairment concurrently enhanced glutamine metabolic flux in senescent NPC,thereby augmenting their survival fitness.Transcriptomic profiling demonstrated that CMA reactivation in senescent NPC facilitated fate transition from senescence to apoptosis,mediated by decreased glutamine flux via GLUL degradation.Therefore,CMA exerts protective effects against IDD by maintaining equilibrium between premature senescence and senolysis.This study elucidates CMA’s regulatory role in SASP-mediated senescence amplification circuits,providing novel therapeutic insights for IDD and other age-related pathologies.
基金supported by the Hebei Natural Science Foundation(Grant No.H2022110019).
文摘Diabetic kidney disease(DKD)has emerged as one of the leading causes of chronic kidney disease and end-stage renal disease worldwide.In the progression of DKD,renal tubular injury plays a pivotal role,with stress-induced senescence of renal tubular epithelial cells(RTECs)being a critical cellular event contributing to tubular damage in DKD.Recent studies have revealed that multiple mechanisms,including oxidative stress,mitochondrial autophagy,endoplasmic reticulum stress,and epigenetic modifications,can induce stress-induced senescence in RTECs,thereby driving the progression of DKD.In recent years,research has demonstrated that traditional Chinese medicine(TCM)can regulate these mechanisms through multiple targets and key pathways,inhibiting stress-induced senescence in RTECs and ameliorating the progression of DKD.TCM has been widely applied in clinical practice with proven efficacy.This article systematically summarizes the concept of cellular senescence,delves into the relationship between stress-induced senescence of RTECs and DKD,analyzes the mechanisms underlying the formation of stress-induced senescence in RTECs within the context of DKD,and reviews the research progress of TCM in anti-senescence treatment for DKD.The aim is to provide a reference for future research and the development of novel therapeutic strategies.
基金supported by the National Natural Science Foundation of China(32171347)the Foundation of Leading Talents from Shanghai Health Commission(2022XD038)+1 种基金Training Program for Research Physicians in Innovation,the Funda-mental Research Funds for the Central Universities(YG2023QNA23)Transforma-tion from shanghai hospital development center(SHDC2022CRD002).
文摘Stem cells play a crucial role in maintaining tissue regenerative capacity and homeostasis.However,mechanisms associated with stem cell senescence require further investigation.In this study,we conducted a proteomic analysis of human dental pulp stem cells(HDPSCs)obtained from individuals of various ages.Our findings showed that the expression of NUP62 was decreased in aged HDPSCs.We discovered that NUP62 alleviated senescence-associated phenotypes and enhanced differentiation potential both in vitro and in vivo.Conversely,the knocking down of NUP62 expression aggravated the senescence-associated phenotypes and impaired the proliferation and migration capacity of HDPSCs.Through RNA-sequence and decoding the epigenomic landscapes remodeled induced by NUP62 overexpression,we found that NUP62 helps alleviate senescence in HDPSCs by enhancing the nuclear transport of the transcription factor E2F1.This,in turn,stimulates the transcription of the epigenetic enzyme NSD2.Finally,the overexpression of NUP62 influences the H3K36me2 and H3K36me3 modifications of anti-aging genes(HMGA1,HMGA2,and SIRT6).Our results demonstrated that NUP62 regulates the fate of HDPSCs via NSD2-dependent epigenetic reprogramming.
文摘To determine the effects of preharvest arginine spraying on the nutritional level of broccoli and the mechanism of action of arginine in improving the storage quality of broccoli,arginine spraying(5 mmol/L)was conducted at 0,1,3,and 5 days before harvest.The appearance,respiration rate,mass-loss rate,electrolyte leakage,glucosinolate,ascorbic acid,total phenol,total flavonoid,total sugar and sucrose contents,and sucrose phosphate synthase(SPS),invertase(INV),sucrose synthase synthesis(SSS)and cleavage(SSC)activities of broccoli samples were observed after 0,2,4,6,8,and 10 days of storage.The results showed that spraying arginine at 5 days preharvest(5-ARG)helped to inhibit broccoli respiration during storage,delay electrolyte leakage,and maintain broccoli color.Furthermore,during the growth stage,total sugar accumulation was higher in the 5-ARG group.In addition,during the storage period,sucrose synthesis was accelerated,while sucrose cleavage was inhibited,resulting in more sucrose retention in postharvest broccoli.In conclusion,5-ARG resulted in the accumulation of more nutrients during the growth process and effectively delayed the quality decline during storage,thereby prolonging the shelf life of broccoli.Therefore,this study provides a theoretical basis for improving postharvest storage characteristics of broccoli through preharvest treatments.
文摘Objective The nucleolar protein PES1(Pescadillo homolog 1)plays critical roles in ribosome biogenesis and cell cycle regulation,yet its involvement in cellular senescence remains poorly understood.This study aimed to comprehensively investigate the functional consequences of PES1 suppression in cellular senescence and elucidate the molecular mechanisms underlying its regulatory role.Methods Initially,we assessed PES1 expression patterns in two distinct senescence models:replicative senescent mouse embryonic fibroblasts(MEFs)and doxorubicin-induced senescent human hepatocellular carcinoma HepG2 cells.Subsequently,PES1 expression was specifically downregulated using siRNA-mediated knockdown in these cell lines as well as additional relevant cell types.Cellular proliferation and senescence were assessed by EdU incorporation and SA-β-gal staining assays,respectively.The expression of senescence-associated proteins(p53,p21,and Rb)and SASP factors(IL-6,IL-1β,and IL-8)were analyzed by Western blot or qPCR.Furthermore,Northern blot and immunofluorescence were employed to evaluate pre-rRNA processing and nucleolar morphology.Results PES1 expression was significantly downregulated in senescent MEFs and HepG2 cells.PES1 knockdown resulted in decreased EdU-positive cells and increased SA-β-gal-positive cells,indicating proliferation inhibition and senescence induction.Mechanistically,PES1 suppression activated the p53-p21 pathway without affecting Rb expression,while upregulating IL-6,IL-1β,and IL-8 production.Notably,PES1 depletion impaired pre-rRNA maturation and induced nucleolar stress,as evidenced by aberrant nucleolar morphology.Conclusion Our findings demonstrate that PES1 deficiency triggers nucleolar stress and promotes p53-dependent(but Rb-independent)cellular senescence,highlighting its crucial role in maintaining nucleolar homeostasis and regulating senescence-associated pathways.
基金supported by the Michael Michelson Gift FundNIA grants R01AG073349 (M.V.R.), R01AG044034 (R.F.L.), and R01AG078609 (J.C.)
文摘Intervertebral disc degeneration is a major risk factor contributing to chronic low back and neck pain.While the etiological factors for disc degeneration vary,age is still one of the most important risk factors.Recent studies have shown the promising role of SIRT6 in mammalian aging and skeletal tissue health,however its role in the intervertebral disc health remains unexplored.We investigated the contribution of SIRT6 to disc health by studying the age-dependent spinal phenotype of mice with conditional deletion of Sirt6 in the disc(AcanCreERT2;Sirt6fl/fl).Histological studies showed a degenerative phenotype in knockout mice compared to Sirt6fl/fl control mice at 12 months,which became pronounced at 24 months.RNA-Seq analysis of NP and AF tissues,in vitro quantitative histone analysis,and RNA-seq with ATAC-seq multiomic studies revealed that SIRT6-loss resulted in changes in acetylation and methylation status of specific Histone 3 lysine residues and affected DNA accessibility and transcriptomic landscape.A decrease in autophagy and an increase in DNA damage were also noted in Sirt6-deficient cells.Further mechanistic insights revealed that loss of SIRT6 increased senescence and SASP burden in the disc characterized by increased p21,p19,γH2AX,IL-6,IL-1β,and TGF-βabundance.Taken together,our study highlights the contribution of SIRT6 in modulating DNA damage,autophagy,and cell senescence and its importance in maintaining disc health during aging,thereby underscoring it as a potential therapeutic target to treat intervertebral disc degeneration.
基金funded by the National Key Research and Development Program of China(2022ZD0115703)the National Natural Science Foundation of China(32372196)+1 种基金the Beijing Joint Research Program for Germplasm Innovation and New Variety Breeding(G20220628002)National Natural Science Foundation of China(32250410307)。
文摘Non-destructive time-series assessment of chlorophyll content in flag-leaf(FLC)accurately mimics the senescence rate and the identification of genetic loci associated with senescence provides valuable knowledge to improve yield stability under stressed environments.In this study,we employed both unmanned aerial vehicles(UAVs)equipped with red–green–blue(RGB)camera and ground-based SPAD-502 instrument to conduct temporal phenotyping of senescence.A total of 262 recombinant inbred lines derived from the cross of Zhongmai 578/Jimai 22 were evaluated for senescence-related traits across three environments,spanning from heading to 35 d post-anthesis.The manual senescence rate(MSR)was quantified using the FLC and the active accumulated temperature,and UAV derived vegetation index were utilized to assess the stay-green rate(USG)facilitating the identification of senescent and stay-green lines.Results indicated that higher senescence rates significantly impacted grain yield,primarily by influencing thousand-kernel weight,and plant height.Quantitative trait loci(QTL)mapping for FLC,USG,and MSR using the 50K SNP array identified 38 stable loci associated with RGB-based vegetation indices and senescence-related traits:among which 19 loci related to senescence traits from UAV and FLC were consistently detected across at least two growth stages,with nine loci likely representing novel QTL.This study highlights the potential of UAV-based high-throughput phenotyping and phenology in identifying critical loci associated with senescence rates in wheat,validating the relationship between senescence rates and yield-related traits in wheat,offering valuable opportunities for gene discovery and significant applications in breeding programs.
基金supported by the National Natural Science Foundation of China(Nos.82474164,82374124,82073914,82173874,82274185,82305046 and 82304902)the Natural Science Foundation of Jiangsu Province(Nos.BK20230458 and BK20220467)+1 种基金the General Project of the Natural Science Research of Jiangsu Higher Education Institutions(No.23KJB310017)Young Elite Scientists Sponsorship Program by CACM(No.2022-QNRC2-B15).
文摘Developing and identifying effective medications and targets for treating hepatic fibrosis is an urgent priority.Our previous research demonstrated the efficacy of artesunate(ART)in alleviating liver fibrosis by eliminating activated hepatic stellate cells(HSCs).However,the underlying mechanism remains unclear despite these findings.Notably,endocytic adaptor protein(NUMB)has significant implications for treating hepatic diseases,but current research primarily focuses on liver regeneration and hepatocellular carcinoma.The precise function of NUMB in liver fibrosis,particularly its ability to regulate HSCs,requires further investigation.This study aims to elucidate the role of NUMB in the anti-hepatic fibrosis action of ART in HSCs.We observed that the expression level of NUMB significantly decreased in activated HSCs compared to quiescent HSCs,exhibiting a negative correlation with the progression of liver fibrosis.Additionally,ART induced senescence in activated HSCs through the NUMB/P53 tumor suppressor(P53)axis.We identified NUMB as a crucial regulator of senescence in activated HSCs and as a mediator of ART in determining cell fate.This research examines the specific target of ART in eliminating activated HSCs,providing both theoretical and experimental evidence for the treatment of liver fibrosis.
基金made possible by the National Natural Science Foundation of China (32060422)。
文摘Drought is one of the important stress factors affecting the growth and development processes of wheat in China's arid zones, which severely limits the yield. This study examined the impact of deficit irrigation on the flag leaf protection system and yield of drip-irrigated spring wheat during the growth stages in arid zones. In addition, this study aimed to determine the optimal water supply mode for efficient production under drip irrigation conditions and to provide technical support for water-saving and high-yield cultivation of drip-irrigated wheat. The experiment was conducted with a split plot design using the water-sensitive variety Xinchun 22(XC22) and the drought-tolerant variety Xinchun 6(XC6) as the main plots, while a fully irrigated control(CK, 75–80% FC, where FC is field water holding capacity), mild deficit(T1, 60–65% FC) and moderate deficit(T2, 45–50% FC) at the tillering stage, and mild deficit(J1, 60–65% FC) and moderate deficit(J2, 45–50% FC) at the jointing stage were used as the subplots. Systematic studies were conducted on the regulatory effects of deficit irrigation during the tillering and jointing stages on protective substances, membrane lipid metabolism, endogenous hormones in the flag leaf, and yield of spring wheat. Compared with treatments T2 and J2, treatments T1 and J1 were beneficial for increasing the activities of superoxide dismutase(SOD), peroxidase(POD), and catalase(CAT), the levels of proline(Pro), indole-3-acetic acid(IAA), and zeatin riboside(ZR), and the ratios IAA/abscisic acid(ABA), ZR/ABA, IAA/ZR, and(IAA+ZR)/ABA, while reducing the levels of hydrogen peroxide(H2O2), superoxide anion radicals(O2–·), malondialdehyde(MDA), phosphatidic acid(PA), free fatty acids(FFA), ABA, phospholipase D(PLD), and lipoxygenase(LOX), alleviating flag leaf senescence, and increasing yield. Under treatment T1, the SOD, POD, CAT, and Pro levels of flag leaves in XC6 were 11.14, 8.08, 12.98, and 3.66% higher than those of treatment CK, and under treatment J1, they were 6.43, 4.49, 7.36, and 2.50% higher than those of treatment CK. Under treatment T1 in XC6, the IAA, ZR level of the flag leaf, spike number, grains per spike, 1,000-grain weight and yield were 10.50, 5.79, 3.10, 8.84, 3.78, and 10.52% higher than those of treatment CK, and under treatment J1, they were 5.36, 3.94, 2.40, 3.72, 1.37, and 4.46% higher than those of treatment CK. Compared with XC22, XC6 was more conducive to the improvement of flag leaf protective substances, IAA, ZR, dry matter weight, yield components and yield. The correlation analysis showed significant positive correlations between IAA and ZR with SOD, POD, CAT, proline, and yield. IAA and ZR promoted the enhancement of protective enzyme activities, thereby clearing reactive oxygen species to cope with the oxidative stress caused by drought and achieve the effect of delaying senescence. Principal component analysis showed that yield components and dry matter weight, had direct effects on yield. Mild deficiency during the tillering stage without water stress in other stages could effectively optimize yield components, not only achieving high yield while increasing protective substances, but also reducing the reactive oxygen species content. This strategy can be recommended as a water-saving and high-yield production mode for drip irrigation of spring wheat in Xinjiang, China.
基金funded by National Research Foundation(NRF)of the Ministry of Science and ICT(MSIT),Republic of Korea(Grant Nos.2022R1C1C1002941,2020R1A2C1004273,2020R1A2C1101915)。
文摘Senescence,a crucial developmental process in the life cycle of plants,involves programmed destruction of cellular components of leaves.The onset of senescence is synchronized with other developmental processes for successful reproduction since senescence eventually leads to cell death.Arabinosyltransferase FASCIATED AND BRANCHED 2(FAB2)is known to control meristem proliferation.Here,we show that FAB2 could inhibit premature leaf senescence in tomato plants.Both chemically mutagenized and CRISPR-generated fab2 mutants exhibited excessively accelerated senescence,which resulted in sterility.Transcriptome analysis revealed that FAB2 extended leaf longevity by suppressing transcription of genes highly expressed in mature leaves.Transcription of FAB2 was increased in younger leaves,potentially inhibiting premature leaf senescence.The precocious senescence of fab2 mutants was in contrast to fasciated inflorescence(fin)mutants,which carried mutations in a hydroxyproline O-arabinosyltransferase gene,leading to meristem overproliferation.Our observations indicate that complex genetic hierarchy in the cascade of tomato arabinosyltransferases could control different aspects of developmental processes such as stem cell proliferation and senescence.
基金supported by National Key Research and Development Program of China(2024YFD2300221)China Agricultural Research System(CARS-15–15)+1 种基金Agricultural Scientific and Technological Innovation Project of Shandong Academy of Agricultural Sciences(CXGC2024D03)Dong Hezhong Studio for Popularization of Science and Technology in Salt Tolerant Industrial Crops(202228297).
文摘Premature senescence in Bacillus thuringiensis(Bt)cotton has emerged as a significant challenge to the formation and realization of fiber yield and quality since its commercialization in 1997.Initially,premature senescence was thought to be an inherent trait associated with the Bt gene.However,subsequent research and practice have demonstrated that it is not directly linked to the Bt gene but rather results from a physiological imbalance between the sink and source,as well as between the root and shoot in Bt cotton.This short review provides an overview of the causes,mechanisms,and control measures for premature senescence in Bt cotton.It offers valuable insights for future research and the sustainable application of transgenic crops.
基金supported by the Department of Education of Anhui Province(2024AH051237)the Open Research Fund of State Key Laboratory of Organic Electronics and Information Displays(SKL2023002)+1 种基金the Science and Technology Innovation Guidance Project of Bengbu City(20220127)the College Students’Innovation and Entrepreneurship Training Program(202210367075,S202310367061).
文摘Background:Breast cancer ranks as the most common cancer in women globally,presenting major challenges primarily due to the emergence of resistance to existing therapies and the adverse side effects linked with these treatments.Natural compounds,such as quercetin,a flavonoid found in Artemisia annua,have gained attention for their multi-targeted therapeutic potential.This research aims to investigate the pharmacological effects of quercetin in inducing cellular senescence in breast cancer cells utilizing network pharmacology.Methods:Initially,the active compounds of Artemisia annua were identified through the Traditional Chinese Medicine Systems Pharmacology database.The breast cancer-related genes were gathered from various databases.The intersection between the genes associated with breast cancer and the targets of active pharmaceutical ingredients was analyzed.Additionally,the regulatory network of active ingredients and their targets was researched.Further,protein-protein interaction was acquired from STRING database and core targets were analyzed.The analyses of Gene Ontology functional enrichment and Kyoto Encyclopedia of Genes and Genomes pathway enrichment were conducted utilizing R programming language.Results:In Artemisia annua,18 active compounds were identified along with their associated target proteins,among which quercetin exhibiting the highest number of target proteins.2897 disease-related genes were discovered,and 145 drug-disease intersection targets were selected.The analysis focused on the impact of quercetin on cellular senescence,informed by core target analysis and enrichment results.Molecular docking studies demonstrated the stable binding of quercetin to cyclin-dependent kinase 2(CDK2),which was chosen for experimental validation.Conclusion:The research highlights the promising therapeutic efficacy of quercetin on breast cancer by the induction of cellular senescence,offering valuable biological insights and establishing a foundation for future research.
基金Natural Science Foundation of Changsha city,China,Grant/Award Number:kq2403166Hunan Provincial Clinical Medical Technology Innovation Guiding Project,Grant/Award Number:2020SK53307+4 种基金Basic Public Welfare Research projects of Wenzhou Science and Technology Bureau,Grant/Award Number:Y20240087Natural Science Foundation of Hunan Province,Grant/Award Number:2020JJ8043Start-up Funding for Talented Scientific Research of the First Affiliated Hospital of Wenzhou Medical University,Grant/Award Number:2023QD026Key Project of Hunan Provincial Health Commission,Grant/Award Number:20201902 and C2019133National Natural Science Foundation of China,Grant/Award Number:82472495。
文摘Background:Osteoarthritis(OA)is a long-term degenerative joint disease worsen-ing over time.Aging and chondrocyte senescence contribute to OA progression.MicroRNAs have been confirmed to regulate different cellular processes.They con-tribute to OA pathology and may help to identify novel biomarkers and therapies for OA.Methods:This study used bioinformatics and experimental investigations to analyze and validate differentially expressed miRNAs in OA that might affect chondrocyte apoptosis and senescence.Results:miR-6779 was found to be significantly down-regulated in OA.Seventy-six of the predicted and miR-6779 targeted genes and the OA-associated disease genes overlapped,and these were enriched in cell proliferation,cell apoptosis,and cell cycle.miR-6779 overexpression remarkably attenuated IL-1βeffects on chon-drocytes by reducing MMP3 and MMP13 levels,promoting cell apoptosis,suppress-ing cell senescence,and increasing caspase-3,caspase-9 and reducing P16 and P21 levels.miR-6779 targeted inhibition of X-linked inhibitor of apoptosis protein(XIAP)expression.XIAP knockdown partially improved IL-1β-induced chondrocyte senes-cence and dysfunction.Lastly,when co-transfected with a miR-6779 agomir,the XIAP overexpression vector partially attenuated the effects of miR-6779 overexpression on chondrocytes;miR-6779 improved IL-1β-induced senescence and dysfunction in chondrocytes through targeting XIAP.Conclusion:miR-6779 is down-regulated,and XIAP is up-regulated in OA cartilage and IL-1β-treated chondrocytes.miR-6779 inhibits XIAP expression,thereby promot-ing senescent chondrocyte cell apoptosis and reducing chondrocyte senescence and ECM loss through XIAP.
基金supported by the National Natural Science Foundation of China(32101857 and U21A20218)the China Agricultural University Corresponding Support Research Joint Fund(GSAU-DKZY-2024-001)+1 种基金the Science and Technology Program in Gansu Province,China(24ZDNA008and23JRRA1407)the Fuxi Young Talents Fund of Gansu Agricultural University,China(Gaufx-03Y10).
文摘Intercropping has been widely used in arid and semi-arid regions because of its high yield,stable productivity,and efficient utilization of resources.However,in recent years,the high yield of traditional intercropping is mainly attributed to the large amount of purchased resources such as water and fertilizer,plastic film,and mechanical power.These lead to a decline in cultivated land quality and exacerbate intercrops'premature root and canopy senescence.So,the application of traditional intercropping faces major challenges in crop production.This paper analyzes the manifestations,occurrence mechanisms,and agronomic regulatory pathways of crop senescence.The physiological and ecological characteristics of intercropping to delay root and canopy senescence of crops are reviewed in this paper.The main agronomic regulatory pathways of intercropping to delay root and canopy senescence of crops are based on above-and blow-ground interactions,including collocation of crop varieties,spatial arrangement,water and fertilizer management,and tillage and mulch practices.Future research fields of intercropping to delay root and canopy senescence should focus on the aspects of selecting and breeding special varieties,application of molecular biology techniques,and developing or applying models to predict and evaluate the root and canopy senescence process of intercrops.Comprehensive analysis and evaluation of different research results could provide a basis for enhancing intercropping delay root and canopy senescence through adopting innovative technologies for regulating the physio-ecological characteristics of intercrops.This would support developing and adopting high-yield,efficient,and sustainable intercropping systems in arid and semi-arid areas with high population density,limited land,and abundant light and heat resources.
基金supported by grant from Affiliated Hospital of Nantong University(YJXYY202204)Postgraduate Research&Practice Innovation Program of Jiangsu Province(SJCX24_2063).
文摘Objective:Neuroblastoma(NB)is frequently associated with high-risk pediatric cases that demonstrate limited response to cisplatin,contributing to a poor prognosis.Recent studies have explored the role of tumor cell senescence in increasing sensitivity to this chemotherapy agent.This study aims to identify genes related to cell senescence in children diagnosed with NB,evaluate their influence on cisplatin sensitivity,and investigate potential strategies to enhance the efficacy of chemotherapy.Methods:Gene expression profiles and clinical data were obtained for 498 NB patients from the GEO database(GSE49710).The study focused on identifying genes that were differentially expressed between stage IV and other stages,particularly those linked to cell senescence and cisplatin resistance.To analyze the prognostic significance of these differentially expressed genes,we employed LASSO regression and multivariate Cox proportional hazards models.Transcriptomic and proteomic analyses of 15 NB specimens revealed a significant correlation between Flap endonuclease-1(FEN1)expression levels and both cellular senescence and sensitivity to cisplatin.We quantified FEN1 expression and cisplatin IC50 values in four different NB cell lines.The influence of FEN1 knockdown and overexpression on NB cell proliferation,invasion,and migration was evaluated using cloning assays,transwell assays,and scratch assays.Furthermore,we utilized Western blotting to analyze senescenceassociated proteins p21 and proliferating cell nuclear antigen(PCNA),thereby evaluating the role of FEN1 in cellular senescence.The impact of FEN1 on cisplatin sensitivity was investigated via the CCK-8 cell counting assay.Additionally,we investigated how FEN1 inhibitors might impact NB cell proliferation and enhance the therapeutic efficacy of cisplatin treatment.Results:FEN1 was found to be highly expressed in stage IV NB and showed a strong association with cisplatin sensitivity,establishing it as a critical molecular marker linked to poor patient prognosis.Notably,elevated FEN1 expression correlated with reduced sensitivity to cisplatin,as evidenced by higher IC50 values.In the SH-SY5Y cell line,FEN1 knockdown led to significant reductions in cell proliferation,invasion,and migration,along with an increase inβ-galactosidase staining—indicative of senescence.This knockdown also resulted in elevated levels of the p21 protein and decreased expression of PCNA,concurrently lowering cisplatin IC50 values.Conversely,FEN1 overexpression in the SK-N-SH cell line resulted in enhanced cell proliferation,invasion,and migration.This overexpression was associated with reducedβ-galactosidase staining,decreased levels of p21,and increased expression of PCNA,ultimately resulting in higher cisplatin IC50 values.Importantly,FEN1 inhibitors alone significantly impeded NB cell proliferation,and their combination with cisplatin further amplified this inhibitory effect compared to cisplatin treatment alone.Conclusions:Bioinformatics and sequencing analyses indicate that the senescence-related gene FEN1 is significantly associated with cisplatin sensitivity and adverse prognosis in pediatric NB.FEN1 plays a pivotal role in regulating NB cell proliferation,invasion,and migration,thereby facilitating cancer progression.Furthermore,it influences cisplatin sensitivity through its effects on cellular senescence.FEN1 inhibitors demonstrate potential both as monotherapies and in conjunction with cisplatin,suggesting that targeting FEN1 may be represent a valuable strategy for improving outcomes in high-risk NB patients.
基金supported by the Natural Science Foundation of Ningxia,China(2024AAC02039)the Scientific and Technological Innovation Leadership Talent Program of Ningxia,China(2022GKLRLX07)+1 种基金the National Natural Science Foundation of China(32260727 and 32371924)China Agriculture Research System(CARS-29-zp-6)。
文摘The postharvest senescence phase of table grapes comprises a series of biological processes.MicroRNAs(miRNAs)regulate downstream genes at the post-transcriptional level;however,whether miRNAs are involved in postharvest grape senescence remains unclear.We used small RNA sequencing to identify postharvest-related miRNAs in‘Red Globe'(Vitis vinifera)grapes harvested after 0,30,and 60 d of storage at 4℃(RG0,RG30,RG60).In total,42 known and 219 novel miRNA candidates were obtained.During fruit senescence,the expression of PC-3p-3343_1921,mi R2950,miR395k,miR2111,miR159c,miR169q,PC-5p-1112_4500,and miR167b changed signifcantly(P<0.05).Degradation sequencing identifed 218 targets associated with cell wall organization,tricarboxylic acid(TCA)cycling,pathogen defense,carbon metabolism,hormone signaling,the anthocyanin metabolism pathway,and energy regulation,of which ARF6,GRF3,TCP2,CP1,MYBA2,and WRKY72 were closely related to fruit senescence.We also verified that VIT_00s2146g00010,VIT_02s0012g01750,and VIT_03s0038g00160 with unknown functions are cleaved by senescence-related PC-5p-1112_4500 via the dual luciferase assay,and the transient transformation of grape berries showed that they regulate berry senescence.These results deepen our understanding of the role of mi RNAs in regulating grape berry senescence and prolonging the shelf life of horticultural products.Based on these results,we propose a new theoretical strategy for delaying the postharvest senescence of horticultural products by regulating the expression of key miRNAs(e.g.,PC-5p-1112_4500),thereby extending their shelf life.
文摘Alzheimer’s disease(AD)is a neurodegenerative disease causing the most frequent form of dementia in old age.AD etiology is still uncertain and deposition of abnormal proteins in the brain along with chronic neuroinflammation have been suggested as pathogenic mechanisms of neuronal death.Infections by exogenous neurotropic virus,endogenous retrovirus reactivation,infections by other microbes,and air pollutants may either induce neurodegeneration or activate brain inflammation.Up to 8%of the human genome has a retroviral origin.These ancient retroviruses,also called human endogenous retroviruses,are associated with a clinical history of several neurodegenerative diseases.Under persistent stress,such as chronic infections and inflammation,neurons,and microglia cells may enter a state of division inactivation called cell senescence.Senescent cells are resistant to apoptosis and can release pro-inflammatory molecules promoting the functional decline of tissues and organs and also activate silent viruses.Infections andmutations induced by pollutants can lead to the expression of different endogenous retroviruses,which may contribute to several different diseases,including AD-associated neurodegeneration.Here I discuss that infection by exogenous pathogen,activation of endogenous retrovirus or retrotransposons and pollutants might induce neuronal senescence and cause persistent brain neurodegeneration.Therefore,cell senescence appears to be an emerging mechanism that might contribute to AD neurodegeneration.Finally,treatment of AD patients with senolytic drugs,e.g.,compounds able to kill senescent cells,might show a positive effect on AD progression.
