Aging is a universal biological process characterized by the progressive decline in cellular and tissue function,representing the main risk factor for the development of most chronic human diseases.At the cellular lev...Aging is a universal biological process characterized by the progressive decline in cellular and tissue function,representing the main risk factor for the development of most chronic human diseases.At the cellular level,one hallmark of aging is the accumulation of senescent cells—non-dividing yet metabolically active cells that adopt a unique phenotype,including the senescence-associated secretory phenotype(SASP)(Wang et al.,2024).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
Mesenchymal stem cells(MSCs)are pluripotent stem cells isolated from human tissues.Due to their strong self-renewal capacity,pluripotency,and immunomodulatory properties,MSCs have garnered significant attention in cel...Mesenchymal stem cells(MSCs)are pluripotent stem cells isolated from human tissues.Due to their strong self-renewal capacity,pluripotency,and immunomodulatory properties,MSCs have garnered significant attention in cell therapy and tissue regeneration.However,cellular senescence induced by replication or external stimuli can impair MSC proliferation and differentiation,making it crucial to develop interventions that delay or reverse the senescence process.From a traditional Chinese medicine perspective,senescence stems from spleen and stomach deficiency,kidney deficiency,and related factors;thus,medicines that tonify the kidney and promote Qi and blood circulation play vital roles in anti-senescence therapy.Chinese medicine,characterized by low toxicity and multi-target,multi-functional properties,has become prominent in anti-senescence research.This paper examines the MSC senescence process by discussing its causes,characteristics,and mechanisms,then summarizes how active ingredients in herbal medicines and natural compounds reverse MSC senescence,facilitating the discovery of additional anti-senescence Chinese medicines and their effective components.展开更多
Vascular ageing is increasingly recognised as a key driver of cardiovascular and cerebrovascular disease rather than merely a passive consequence of chronological time.Progressive loss of endothelial regenerative capa...Vascular ageing is increasingly recognised as a key driver of cardiovascular and cerebrovascular disease rather than merely a passive consequence of chronological time.Progressive loss of endothelial regenerative capacity remains central to this process and is characterised by endothelial progenitor cell dysfunction,accumulation of senescent endothelial cells,and aberrant changes in the endothelial secretome.Taken together these alterations contribute to ineffective endothelial repair,chronic(low-grade)vascular inflammation and impaired endothelial barrier integrity and function,ultimately leading to vascular dysfunction.Over the past two decades,accumulating evidence from our group and others has provided mechanistic insight into how oxidative stress,redox imbalance,mitochondrial dysfunction and cellular senescence collectively impair endothelial(barrier)function and compromise overall vascular homeostasis.Age-dependent changes in progenitor cell number and function further limit the capacity of vasculature to respond to damage and stress.More recent work demonstrate that senolytics and senomorphics can preserve endothelial function and delay age-related vascular and cerebral barrier dysfunction in experimental models.This mini review supports an emerging framework that positions defective endothelial renewal as a critical driver of vascular ageing and endothelial dysfunction.We propose that concomitant application of senotherapeutics with progenitor cell-based or secretome-based approaches represents a critical next step in precision vascular medicine.展开更多
Objective:To investigate the effect of a water-soluble nacre extract derived from Pinctada fucata on skeletal muscle aging.Methods:Naturally aged C57BL/6J mice received nacre extract mixed in chow for 12 weeks.Forelim...Objective:To investigate the effect of a water-soluble nacre extract derived from Pinctada fucata on skeletal muscle aging.Methods:Naturally aged C57BL/6J mice received nacre extract mixed in chow for 12 weeks.Forelimb grip strength,hanging performance,and locomotor activity were assessed.Skeletal muscle remodeling and signaling were evaluated by histology and immunostaining for fibrosis,contractile-marker features,senescence-and DNA damage-associated markers,inflammatory signaling,and mitochondrial proteins.Oxidative status was assessed by determining antioxidant capacity,lipid peroxidation,and oxidative DNA damage.Transcriptomic profiling was also performed,and selected targets were validated by quantitative RT-PCR and immunostaining.In addition,differentiated C2C12 myotubes were exposed to doxorubicin and treated with nacre extract;senescence-associated β-galactosidase,DNA damage signaling,and cell viability were measured.Results:Nacre extract increased forelimb grip strength and showed a positive trend in hanging performance without altering spontaneous locomotion.It also reduced collagen deposition,preserved contractile-marker immunoreactivity,attenuated senescence-and inflammation-associated signals,and increased mitochondrial protein immunoreactivity.Oxidative DNA damage was notably reduced by nacre extract.Transcriptomics indicated modulation of stress/redox programs and increased neurotrophic tyrosine kinase receptor type 2 expression,which were supported by tissue-level validation.In C2C12 myotubes,nacre extract suppressed doxorubicin-induced senescence-associated phenotypes without loss of cell viability.Conclusions:Water-soluble nacre extract mitigates skeletal muscle aging through coordinated modulation of oxidative stress,inflammation,mitochondrial features,and cellular senescence.展开更多
Objective:The luminal androgen receptor(LAR)subtype of triple-negative breast cancer(TNBC)differentiation displays low proliferation yet strong metastatic potential and a poor chemotherapy response.This study aimed to...Objective:The luminal androgen receptor(LAR)subtype of triple-negative breast cancer(TNBC)differentiation displays low proliferation yet strong metastatic potential and a poor chemotherapy response.This study aimed to define the molecular basis of the LAR subtype and identify actionable therapeutic targets.Methods:Comprehensive multi-omic analyses were performed on the FUSCC-TNBC cohort,integrating whole-exome sequencing,RNA sequencing,and functional validation in vitro and in vivo.Somatic mutation profiling,gene set enrichment analysis(GSEA),and weighted gene co-expression network analysis(WGCNA)were used to define genomic and transcriptomic signatures.A machine learning model using the Mime1 package was applied to derive a senescence-associated prognostic signature(LAR-S)and validation in external cohorts.Immune deconvolution was performed to decipher the tumor microenvironment.Functional assays,patient-derived organoids(PDOs),and TS/V mouse models were used to evaluate therapeutic responses to senescence-modulating agent and immunotherapy combinations.Results:The LAR subtype was enriched for PIK3CA,PTEN,and ERBB2 kinase domain mutations.Functional studies confirmed ERBB2 variants(e.g.,V777L and E698_P699delinsA)as oncogenic drivers conferring sensitivity to neratinib.Transcriptomic analyses revealed a dominant cellular senescence program associated with immune suppression.The LAR-S signature stratified survival across cohorts and predicted immunotherapy resistance.Targeting cellular senescence inhibited LAR subtype organoid growth and when combined with anti-PD-1 therapy synergistically suppressed tumor growth in vivo.Conclusions:The LAR subtype harbors two therapeutic vulnerabilities:ERBB2 mutation-driven kinase activation;and senescencemediated immune evasion.The LAR-S signature enables precise patient stratification and supports senescence-targeted and immunotherapy combination strategies as promising approaches for this refractory TNBC subtype.展开更多
Neuronal degeneration and inflammation are hallmark features of spinal cord injury that severely hinder functional recovery.As key regulators of the post-injury microenvironment,macrophages can promote either tissue r...Neuronal degeneration and inflammation are hallmark features of spinal cord injury that severely hinder functional recovery.As key regulators of the post-injury microenvironment,macrophages can promote either tissue repair or exacerbate damage.Among macrophage secreted factors,transforming growth factor-beta 1 has emerged as a critical mediator of pathological changes.In this study,we show the pivotal role of macrophage-derived transforming growth factor-beta 1 in driving neuronal senescence and impairing functional recovery after spinal cord injury.In a mouse spinal cord injury model,transforming growth factor-beta 1 levels were significantly increased at the injury site,accompanied by increased mothers against decapentaplegic homolog 2(SMAD2)phosphorylation and upregulation of neuronal senescence markers such as p16INK4a andβ-galactosidase activity.Treatment with LY-364947,a SMAD2 phosphorylation inhibitor,markedly reduced the number of senescent neurons,mitigated tissue degeneration,and improved motor function recovery.Additionally,macrophage depletion using clodronate liposomes lowered transforming growth factor-beta 1 levels at the injury site and attenuated neuronal senescence.These findings highlight the transforming growth factor-beta 1-SMAD2 signaling axis as a potential therapeutic target to reduce neuronal senescence and enhance functional recovery following spinal cord injury.展开更多
Gastric cancer is a significant global and Chinese health issue,primarily linked to Helicobacter pylori(H.pylori)infection[1],classified as a carcinogen by the U.S.in 2022.The Correa cascade model outlines the progres...Gastric cancer is a significant global and Chinese health issue,primarily linked to Helicobacter pylori(H.pylori)infection[1],classified as a carcinogen by the U.S.in 2022.The Correa cascade model outlines the progression from H.pylori gastritis cancer via precancerous stages[2].Current antibiotic-based treatment regimens are facing increasingly severe challenges of drug resistance[3].展开更多
Increasing photosynthetic capacity by extending canopy longevity during grain filling using slow senescing stay-green genotypes is a possible means to improve yield in wheat. Ethyl methanesulfonate （EMS） mutated whe...Increasing photosynthetic capacity by extending canopy longevity during grain filling using slow senescing stay-green genotypes is a possible means to improve yield in wheat. Ethyl methanesulfonate （EMS） mutated wheat lines （Triticum aestivum L. cv. Paragon） were screened for fast and slow canopy senescence to investigate the impact on yield and nitrogen partitioning. Stay-green and fast-senescing lines with similar anthesis dates were characterised in detail. Delayed senescence was only apparent at higher nitrogen supply with low nitrogen supply enhancing the rate of senescence in all lines. In the stay-green line 3 （SG3）, on a whole plant basis, tiller and seed number increased whilst thousand grain weight （TGW） decreased; although a greater N uptake was observed in the main tiller, yield was not affected. In fast-senescing line 2 （FS2）, yield decreased, principally as a result of decreased TGW. Analysis of N-partitioning in the main stem indicated that although the slow-senescing line had lower biomass and consequently less nitrogen in all plant parts, the proportion of biomass and nitrogen in the flag leaf was greater at anthesis compared to the other lines; this contributed to the grain N and yield of the slow-senescing line at maturity in both the main tiller and in the whole plant. A field trial confirmed senescence patterns of the two lines, and the negative impact on yield for FS2 and a positive impact for SG3 at low N only. The lack of increased yield in the slow-senescing line was likely due to decreased biomass and additionally a possible sink limitation.展开更多
Light quality significantly affects photosynthetic efficiency in plants. The mechanisms for how light quality affects photosynthesis in grape is poorly understood. Therefore, to investigate the effects of different li...Light quality significantly affects photosynthetic efficiency in plants. The mechanisms for how light quality affects photosynthesis in grape is poorly understood. Therefore, to investigate the effects of different light qualities on chloroplast ultrastructure and photosynthesis efficiency, two grape cultivars ‘Italia'(slower speed of leaf senescence) and ‘Centennial Seedless'(faster speed of leaf senescence) grown under protected and delayed conditions were used. The three treatments, replicated three times, were control(no supplemental lighting), red light and blue light. Chlorophyll content, net photosynthetic rate, and the ratio of F_v/F_m significantly increased in red light relative to the control. The opposite trend was observed in blue light in the early phase of leaf senescence. At later stages, physiological indexes were gradually higher than that of control, resulting in a delay in leaf senescence. Compared to the control, red and blue light both significantly increased the chlorophyll a/b ratio. Electron microscopy showed that blue light caused severe damage to the fine structure of chloroplasts at early stages of leaf senescence, but effects at later stages of leaf senescence became less severe compared to the control. The degradation of chloroplast ultrastructure was apparently delayed in red light throughout the experimental timeframe compared to other treatments. In this experiment, ‘Italia' showed higher chlorophyll content, net photosynthetic rate, ratios of F_v/F_m, chlorophyll a/b and better preserved chloroplast ultrastructure relative to ‘Centennial Seedless', resulting in a slower rate of leaf senescence.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
Nigella sativa L.seeds have been traditionally utilized in Chinese folk medicine for centuries to treat vitiligo.This study revealed that the ethanolic extract of Nigella sativa L.(HZC)enhances melanogenesis and mitig...Nigella sativa L.seeds have been traditionally utilized in Chinese folk medicine for centuries to treat vitiligo.This study revealed that the ethanolic extract of Nigella sativa L.(HZC)enhances melanogenesis and mitigates oxidative stress-induced cellular senescence and dysfunction in melanocytes.In accordance with established protocols,the ethanol fraction from Nigella sativa L.seeds was extracted,concentrated,and lyophilized to evaluate its herbal effects via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)assays,tyrosinase activity evaluation,measurement of cellular melanin contents,scratch assays,senescence-associatedβ-galactosidase(SA-β-gal)staining,enzyme-linked immunosorbent assay(ELISA),and Western blot analysis for expression profiling of experimentally relevant proteins.The results indicated that HZC significantly enhanced tyrosinase activity and melanin content while notably increasing the protein expression levels of Tyr,Mitf,and gp100 in B16F10 cells.Furthermore,HZC effectively mitigated oxidative stress-induced cellular senescence,improved melanocyte condition,and rectified various functional impairments associated with melanocyte dysfunction.These findings suggest that HZC increases melanin synthesis in melanocytes through the activation of the MAPK,PKA,and Wnt signaling pathways.In addition,HZC attenuates oxidative damage induced by H2O2 therapy by activating the nuclear factor E2-related factor 2-antioxidant response element(Nrf2-ARE)pathway and enhancing the activity of downstream antioxidant enzymes,thus preventing premature senescence and dysfunction in melanocytes.展开更多
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
BACKGROUND Extracellular vesicles derived from mesenchymal stromal cells(MSC-EVs)can be used for anti-aging therapy and treating various aging-related diseases.However,the clinical application of MSC-EVs is still limi...BACKGROUND Extracellular vesicles derived from mesenchymal stromal cells(MSC-EVs)can be used for anti-aging therapy and treating various aging-related diseases.However,the clinical application of MSC-EVs is still limited,mainly due to insufficient in-formation on the preparation process,quality,and mechanism of action of MSC-EVs.To study the biological effects of MSC-EVs in regulating cellular senescence.METHODS In this study,we developed a clinical-grade production process for MSC-EVs and defined the release criteria for products suitable for human use.To support the clinical use of our product as a therapeutic agent,we performed efficacy assays to evaluate the anti-aging capacity of MSC-EVs in vitro and in vivo.RESULTS The functional analysis results revealed that MSC-EVs significantly reduced the levels of senescence-associatedβ-galactosidase,matrix metallopeptidase 1,P21,and interleukin-1βand increased the level of collagen I in a naturally aged cell model of human dermal fibroblasts.Similarly,treatment with MSC-EVs effectively improved D-gal-induced subacute aging in mice,aging-related histopathological changes,oxidative stress,and aging-related gene expression.CONCLUSION These findings indicate that MSC-EVs can partially alleviate D-gal-induced senescence by reducing oxidative stress and regulating metabolism.Overall,these findings strongly suggest that MSC-EVs hold promise for aging therapy.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
The intensified kernel position effect is a common phenomenon in maize production under higher plant density,which limits crop productivity.Subsoiling is an effective agronomic practice for improving crop productivity...The intensified kernel position effect is a common phenomenon in maize production under higher plant density,which limits crop productivity.Subsoiling is an effective agronomic practice for improving crop productivity.To clarify the effect of subsoiling before winter wheat on the kernel position effect of densely grown summer maize and its regulatory mechanism,field experiments were conducted during the 2020-2021 and 2021-2022 growing seasons using a split-plot design.The main plots included two tillage practices:conventional tillage practice(CT)and subsoiling before the sowing of winter wheat(SS);and the subplots consisted of three plant densities(D1-D3 at 6.0×10~4,7.5×10~4,and 9.0×10~4 plants ha-1).Compared with CT,SS alleviated the kernel position effect by increasing the weight ratio of inferior to superior kernels(WR)in the D2 and D3 treated plants.The higher WR of SS treated plants contributed largely to the improved flling of inferior kernels.Under the same plant density,SS signifcantly improved the root dry matter accumulation(DMA)and antioxidant enzyme activities(superoxide dismutase(SOD)and peroxidase(POD)),and it reduced the malondialdehyde(MDA)content,especially for the plants grown under higher plant densities.These results indicated that SS delayed the root senescence,which is associated with the reduced soil bulk density.In addition,compared with CT,SS increased the leaf chlorophyll content from 20 days after silking to physiological maturity and the post-silking leaf area duration,and it reduced the post-silking leaf chlorophyll reduction rate and leaf area reduction rate,indicating that the post-silking leaf senescence had been alleviated.Under the same plant density,the post-silking DMA of SS was obviously higher than that of CT,which was probably related to the improved leaf area duration and photosynthetic enzyme activities(phosphoenolpyruvate carboxylase(PEPC)and Rubisco).The correlation analysis revealed that the main mechanism of SS in alleviating the kernel position effect of densely grown summer maize is as follows:SS delays the post-silking root-shoot senescence by regulating soil physical properties,and further improves the post-silking DMA and flling of inferior kernels,which ultimately alleviates the kernel position effect and improves grain yield.The results of this study provide new theoretical support for the promotion of summer maize yield by subsoiling before winter wheat.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
Improving salt tolerance and mitigating senescence in the presence of high salinity are crucial for sustaining agricultural productivity.Previous research has demonstrated that hydrogen peroxide(H_(2)O_(2)),specifical...Improving salt tolerance and mitigating senescence in the presence of high salinity are crucial for sustaining agricultural productivity.Previous research has demonstrated that hydrogen peroxide(H_(2)O_(2)),specifically H_(2)O_(2)derived from roots and mediated by the respiratory burst oxidase homolog(NADPH),plays a significant role in regulating ion and plant hormone homeostasis in glycophytic plants,such as Arabidopsis.However,the extent to which root-derived H_(2)O_(2)fulfils similar functions in halophytic plants remains uncertain.Therefore,our study aimed to explore the potential contribution of root-sourced H_(2)O_(2)in delaying leaf senescence induced by high salinity,utilizing seashore paspalum as a model halophytic plant.The application of the NADPH-oxidase inhibitor DPI,coupled with a series of leaf senescence analyses,we revealed that root-derived H_(2)O_(2)significantly retards salt-induced leaf senescence.Furthermore,through the application of hormone analysis,lipidomics,ionomics,Non-invasive Micro-test Technology(NMT),and transcriptomics,we established that NADPH-dependent H_(2)O_(2)induced by salt stress in the roots was indispensable for maintaining the balance of the aging hormone,jasmonic acid(JA),and sodium ion homeostasis within this halophytic plant.Finally,by utilizing AtrbohD Arabidopsis mutants and virus-induced gene silencing(VIGs)in Paspalum vaginatum,we demonstrated the pivotal role played by root-sourced H_(2)O_(2)in upholding JA homeostasis and regulating JA-triggered leaf senescence in P.vaginatum.This study offers novel insights into the mechanisms that govern plant leaf senescence and its response to salinity-induced stress.展开更多
Aging is a pivotal risk factor for intervertebral disc degeneration(IVDD)and chronic low back pain(LBP).The restoration of aging nucleus pulposus cells(NPCs)to a youthful epigenetic state is crucial for IVDD treatment...Aging is a pivotal risk factor for intervertebral disc degeneration(IVDD)and chronic low back pain(LBP).The restoration of aging nucleus pulposus cells(NPCs)to a youthful epigenetic state is crucial for IVDD treatment,but remains a formidable challenge.Here,we proposed a strategy to partially reprogram and reinstate youthful epigenetics of senescent NPCs by delivering a plasmid carrier that expressed pluripotency-associated genes(Oct4,Klf4 and Sox2)in Cavin2-modified exosomes(OKS@M-Exo)for treatment of IVDD and alleviating LBP.The functional OKS@M-Exo efficaciously alleviated senescence markers(p16^(INK4a),p21^(CIP1)and p53),reduced DNA damage and H4K20me3 expression,as well as restored proliferation ability and metabolic balance in senescent NPCs,as validated through in vitro experiments.In a rat model of IVDD,OKS@M-Exo maintained intervertebral disc height,nucleus pulposus hydration and tissue structure,effectively ameliorated IVDD via decreasing the senescence markers.Additionally,OKS@MExo reduced nociceptive behavior and downregulated nociception markers,indicating its efficiency in alleviating LBP.The transcriptome sequencing analysis also demonstrated that OKS@M-Exo could decrease the expression of age-related pathways and restore cell proliferation.Collectively,reprogramming by the OKS@M-Exo to restore youthful epigenetics of senescent NPCs may hold promise as a therapeutic platform to treat IVDD.展开更多
基金NIH NIA1RO1AG061879 and 5PO1AG066591(to LME)FONDAP Program 15150012,ECOS-A NID(ECOS230034)the US Army Medical Research Acquisition Activity(USAMRAA)AL2201415(to CH)。
文摘Aging is a universal biological process characterized by the progressive decline in cellular and tissue function,representing the main risk factor for the development of most chronic human diseases.At the cellular level,one hallmark of aging is the accumulation of senescent cells—non-dividing yet metabolically active cells that adopt a unique phenotype,including the senescence-associated secretory phenotype(SASP)(Wang et al.,2024).
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 Zhejiang Provincial Natural Science Foundation of China(No.LQ23H290006)the National Natural Science Foundation of China(No.82204781)+2 种基金the Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province(No.2020E10021)Zhejiang Provincial Program for the Cultivation of High-level Innovative Health Talents(No.ZWB-2020-18)Zhejiang Provincial Traditional Chinese Medicine Science and Technology Project(No.2023ZR119).
文摘Mesenchymal stem cells(MSCs)are pluripotent stem cells isolated from human tissues.Due to their strong self-renewal capacity,pluripotency,and immunomodulatory properties,MSCs have garnered significant attention in cell therapy and tissue regeneration.However,cellular senescence induced by replication or external stimuli can impair MSC proliferation and differentiation,making it crucial to develop interventions that delay or reverse the senescence process.From a traditional Chinese medicine perspective,senescence stems from spleen and stomach deficiency,kidney deficiency,and related factors;thus,medicines that tonify the kidney and promote Qi and blood circulation play vital roles in anti-senescence therapy.Chinese medicine,characterized by low toxicity and multi-target,multi-functional properties,has become prominent in anti-senescence research.This paper examines the MSC senescence process by discussing its causes,characteristics,and mechanisms,then summarizes how active ingredients in herbal medicines and natural compounds reverse MSC senescence,facilitating the discovery of additional anti-senescence Chinese medicines and their effective components.
文摘Vascular ageing is increasingly recognised as a key driver of cardiovascular and cerebrovascular disease rather than merely a passive consequence of chronological time.Progressive loss of endothelial regenerative capacity remains central to this process and is characterised by endothelial progenitor cell dysfunction,accumulation of senescent endothelial cells,and aberrant changes in the endothelial secretome.Taken together these alterations contribute to ineffective endothelial repair,chronic(low-grade)vascular inflammation and impaired endothelial barrier integrity and function,ultimately leading to vascular dysfunction.Over the past two decades,accumulating evidence from our group and others has provided mechanistic insight into how oxidative stress,redox imbalance,mitochondrial dysfunction and cellular senescence collectively impair endothelial(barrier)function and compromise overall vascular homeostasis.Age-dependent changes in progenitor cell number and function further limit the capacity of vasculature to respond to damage and stress.More recent work demonstrate that senolytics and senomorphics can preserve endothelial function and delay age-related vascular and cerebral barrier dysfunction in experimental models.This mini review supports an emerging framework that positions defective endothelial renewal as a critical driver of vascular ageing and endothelial dysfunction.We propose that concomitant application of senotherapeutics with progenitor cell-based or secretome-based approaches represents a critical next step in precision vascular medicine.
文摘Objective:To investigate the effect of a water-soluble nacre extract derived from Pinctada fucata on skeletal muscle aging.Methods:Naturally aged C57BL/6J mice received nacre extract mixed in chow for 12 weeks.Forelimb grip strength,hanging performance,and locomotor activity were assessed.Skeletal muscle remodeling and signaling were evaluated by histology and immunostaining for fibrosis,contractile-marker features,senescence-and DNA damage-associated markers,inflammatory signaling,and mitochondrial proteins.Oxidative status was assessed by determining antioxidant capacity,lipid peroxidation,and oxidative DNA damage.Transcriptomic profiling was also performed,and selected targets were validated by quantitative RT-PCR and immunostaining.In addition,differentiated C2C12 myotubes were exposed to doxorubicin and treated with nacre extract;senescence-associated β-galactosidase,DNA damage signaling,and cell viability were measured.Results:Nacre extract increased forelimb grip strength and showed a positive trend in hanging performance without altering spontaneous locomotion.It also reduced collagen deposition,preserved contractile-marker immunoreactivity,attenuated senescence-and inflammation-associated signals,and increased mitochondrial protein immunoreactivity.Oxidative DNA damage was notably reduced by nacre extract.Transcriptomics indicated modulation of stress/redox programs and increased neurotrophic tyrosine kinase receptor type 2 expression,which were supported by tissue-level validation.In C2C12 myotubes,nacre extract suppressed doxorubicin-induced senescence-associated phenotypes without loss of cell viability.Conclusions:Water-soluble nacre extract mitigates skeletal muscle aging through coordinated modulation of oxidative stress,inflammation,mitochondrial features,and cellular senescence.
基金funding from the Ministry of Science and Technology of China(Grant Nos.2023YFF1205003,2023YFF0613304,and 2023YFC3402504)the National Key R&D Program of China(Grant No.2023YFF0613300,2023YFF1205003)the National Natural Science Foundation of China(Grant Nos.82473499,82272957,and 82303735).
文摘Objective:The luminal androgen receptor(LAR)subtype of triple-negative breast cancer(TNBC)differentiation displays low proliferation yet strong metastatic potential and a poor chemotherapy response.This study aimed to define the molecular basis of the LAR subtype and identify actionable therapeutic targets.Methods:Comprehensive multi-omic analyses were performed on the FUSCC-TNBC cohort,integrating whole-exome sequencing,RNA sequencing,and functional validation in vitro and in vivo.Somatic mutation profiling,gene set enrichment analysis(GSEA),and weighted gene co-expression network analysis(WGCNA)were used to define genomic and transcriptomic signatures.A machine learning model using the Mime1 package was applied to derive a senescence-associated prognostic signature(LAR-S)and validation in external cohorts.Immune deconvolution was performed to decipher the tumor microenvironment.Functional assays,patient-derived organoids(PDOs),and TS/V mouse models were used to evaluate therapeutic responses to senescence-modulating agent and immunotherapy combinations.Results:The LAR subtype was enriched for PIK3CA,PTEN,and ERBB2 kinase domain mutations.Functional studies confirmed ERBB2 variants(e.g.,V777L and E698_P699delinsA)as oncogenic drivers conferring sensitivity to neratinib.Transcriptomic analyses revealed a dominant cellular senescence program associated with immune suppression.The LAR-S signature stratified survival across cohorts and predicted immunotherapy resistance.Targeting cellular senescence inhibited LAR subtype organoid growth and when combined with anti-PD-1 therapy synergistically suppressed tumor growth in vivo.Conclusions:The LAR subtype harbors two therapeutic vulnerabilities:ERBB2 mutation-driven kinase activation;and senescencemediated immune evasion.The LAR-S signature enables precise patient stratification and supports senescence-targeted and immunotherapy combination strategies as promising approaches for this refractory TNBC subtype.
基金supported by grants from Tianjin Key Medical Discipline(Specialty)Construct Project,No.TJYXZDXK-027A(to SF)National Key Research and Development Project of Stem Cell and Transformation Research,No.2019YFA0112100(to SF)+3 种基金the National Natural Science Foundation of China,Nos.81930070(to SF),82402825(to XS)Tianjin Health Science and Technology Project Key Discipline Special Project,No.hUCMSC preferred subgroup,No.TJWJ2022XK002(to SF)2022 Beijing-Tianjin-Hebei Basic Research Cooperation Project,No.22JCZXJC00050(to SF)Youth Research Incubation Fund of School of Basic Medical Sciences,Tianjin Medical University,No.023FY05(to XS).
文摘Neuronal degeneration and inflammation are hallmark features of spinal cord injury that severely hinder functional recovery.As key regulators of the post-injury microenvironment,macrophages can promote either tissue repair or exacerbate damage.Among macrophage secreted factors,transforming growth factor-beta 1 has emerged as a critical mediator of pathological changes.In this study,we show the pivotal role of macrophage-derived transforming growth factor-beta 1 in driving neuronal senescence and impairing functional recovery after spinal cord injury.In a mouse spinal cord injury model,transforming growth factor-beta 1 levels were significantly increased at the injury site,accompanied by increased mothers against decapentaplegic homolog 2(SMAD2)phosphorylation and upregulation of neuronal senescence markers such as p16INK4a andβ-galactosidase activity.Treatment with LY-364947,a SMAD2 phosphorylation inhibitor,markedly reduced the number of senescent neurons,mitigated tissue degeneration,and improved motor function recovery.Additionally,macrophage depletion using clodronate liposomes lowered transforming growth factor-beta 1 levels at the injury site and attenuated neuronal senescence.These findings highlight the transforming growth factor-beta 1-SMAD2 signaling axis as a potential therapeutic target to reduce neuronal senescence and enhance functional recovery following spinal cord injury.
基金supported by the National Natural Science Foundation of China(82573571,82470594)National Science and Technology Major Project(2025ZD0545300)+2 种基金Shanghai 2025 Basic Research Plan Natural Science Foundation(25ZR1401393)Key Project of Heilongjiang Provincial Joint Fund of Natural Science Foundation(ZL2025H017)the First Batch of Open Topics of the Shanghai Key Laboratory of Nautical Medicine and Translation of Drugs and Medical Devices(2025QN13).
文摘Gastric cancer is a significant global and Chinese health issue,primarily linked to Helicobacter pylori(H.pylori)infection[1],classified as a carcinogen by the U.S.in 2022.The Correa cascade model outlines the progression from H.pylori gastritis cancer via precancerous stages[2].Current antibiotic-based treatment regimens are facing increasingly severe challenges of drug resistance[3].
基金Derkx AP received support from the Lawes Agricultural TrustRothamsted Research and the John Innes Centre receive funding from the Biotechnology and Biological Research Council of the United Kingdom
文摘Increasing photosynthetic capacity by extending canopy longevity during grain filling using slow senescing stay-green genotypes is a possible means to improve yield in wheat. Ethyl methanesulfonate （EMS） mutated wheat lines （Triticum aestivum L. cv. Paragon） were screened for fast and slow canopy senescence to investigate the impact on yield and nitrogen partitioning. Stay-green and fast-senescing lines with similar anthesis dates were characterised in detail. Delayed senescence was only apparent at higher nitrogen supply with low nitrogen supply enhancing the rate of senescence in all lines. In the stay-green line 3 （SG3）, on a whole plant basis, tiller and seed number increased whilst thousand grain weight （TGW） decreased; although a greater N uptake was observed in the main tiller, yield was not affected. In fast-senescing line 2 （FS2）, yield decreased, principally as a result of decreased TGW. Analysis of N-partitioning in the main stem indicated that although the slow-senescing line had lower biomass and consequently less nitrogen in all plant parts, the proportion of biomass and nitrogen in the flag leaf was greater at anthesis compared to the other lines; this contributed to the grain N and yield of the slow-senescing line at maturity in both the main tiller and in the whole plant. A field trial confirmed senescence patterns of the two lines, and the negative impact on yield for FS2 and a positive impact for SG3 at low N only. The lack of increased yield in the slow-senescing line was likely due to decreased biomass and additionally a possible sink limitation.
基金supported by the grants from National Natural Science Foundation of China(No.41101573)China Agriculture Research System(nycytx-30-zp)CAAS-ASTIP-2015-RIP-04
文摘Light quality significantly affects photosynthetic efficiency in plants. The mechanisms for how light quality affects photosynthesis in grape is poorly understood. Therefore, to investigate the effects of different light qualities on chloroplast ultrastructure and photosynthesis efficiency, two grape cultivars ‘Italia'(slower speed of leaf senescence) and ‘Centennial Seedless'(faster speed of leaf senescence) grown under protected and delayed conditions were used. The three treatments, replicated three times, were control(no supplemental lighting), red light and blue light. Chlorophyll content, net photosynthetic rate, and the ratio of F_v/F_m significantly increased in red light relative to the control. The opposite trend was observed in blue light in the early phase of leaf senescence. At later stages, physiological indexes were gradually higher than that of control, resulting in a delay in leaf senescence. Compared to the control, red and blue light both significantly increased the chlorophyll a/b ratio. Electron microscopy showed that blue light caused severe damage to the fine structure of chloroplasts at early stages of leaf senescence, but effects at later stages of leaf senescence became less severe compared to the control. The degradation of chloroplast ultrastructure was apparently delayed in red light throughout the experimental timeframe compared to other treatments. In this experiment, ‘Italia' showed higher chlorophyll content, net photosynthetic rate, ratios of F_v/F_m, chlorophyll a/b and better preserved chloroplast ultrastructure relative to ‘Centennial Seedless', resulting in a slower rate of leaf senescence.
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.
基金supported by the National Natural Science Foundation of China (Nos.81973410 and 82473537)the Independent Research Fund of Yunnan Characteristic Plant Extraction Laboratory (Nos.2022YKZY002 and 2022YKZY004)。
文摘Nigella sativa L.seeds have been traditionally utilized in Chinese folk medicine for centuries to treat vitiligo.This study revealed that the ethanolic extract of Nigella sativa L.(HZC)enhances melanogenesis and mitigates oxidative stress-induced cellular senescence and dysfunction in melanocytes.In accordance with established protocols,the ethanol fraction from Nigella sativa L.seeds was extracted,concentrated,and lyophilized to evaluate its herbal effects via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)assays,tyrosinase activity evaluation,measurement of cellular melanin contents,scratch assays,senescence-associatedβ-galactosidase(SA-β-gal)staining,enzyme-linked immunosorbent assay(ELISA),and Western blot analysis for expression profiling of experimentally relevant proteins.The results indicated that HZC significantly enhanced tyrosinase activity and melanin content while notably increasing the protein expression levels of Tyr,Mitf,and gp100 in B16F10 cells.Furthermore,HZC effectively mitigated oxidative stress-induced cellular senescence,improved melanocyte condition,and rectified various functional impairments associated with melanocyte dysfunction.These findings suggest that HZC increases melanin synthesis in melanocytes through the activation of the MAPK,PKA,and Wnt signaling pathways.In addition,HZC attenuates oxidative damage induced by H2O2 therapy by activating the nuclear factor E2-related factor 2-antioxidant response element(Nrf2-ARE)pathway and enhancing the activity of downstream antioxidant enzymes,thus preventing premature senescence and dysfunction in melanocytes.
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 Ministry of Science and Technology of China,No.2021YFA1101502。
文摘BACKGROUND Extracellular vesicles derived from mesenchymal stromal cells(MSC-EVs)can be used for anti-aging therapy and treating various aging-related diseases.However,the clinical application of MSC-EVs is still limited,mainly due to insufficient in-formation on the preparation process,quality,and mechanism of action of MSC-EVs.To study the biological effects of MSC-EVs in regulating cellular senescence.METHODS In this study,we developed a clinical-grade production process for MSC-EVs and defined the release criteria for products suitable for human use.To support the clinical use of our product as a therapeutic agent,we performed efficacy assays to evaluate the anti-aging capacity of MSC-EVs in vitro and in vivo.RESULTS The functional analysis results revealed that MSC-EVs significantly reduced the levels of senescence-associatedβ-galactosidase,matrix metallopeptidase 1,P21,and interleukin-1βand increased the level of collagen I in a naturally aged cell model of human dermal fibroblasts.Similarly,treatment with MSC-EVs effectively improved D-gal-induced subacute aging in mice,aging-related histopathological changes,oxidative stress,and aging-related gene expression.CONCLUSION These findings indicate that MSC-EVs can partially alleviate D-gal-induced senescence by reducing oxidative stress and regulating metabolism.Overall,these findings strongly suggest that MSC-EVs hold promise for aging therapy.
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fnancially supported by the Natural Science Foundation of Hebei Province,China(C2021301004)the State Key Laboratory of North China Crop Improvement and Regulation,China(NCCIR2023KF-10)the HAAFS Science and Technology Innovation Special Project,China(2022KJCXZX-LYS-9)。
文摘The intensified kernel position effect is a common phenomenon in maize production under higher plant density,which limits crop productivity.Subsoiling is an effective agronomic practice for improving crop productivity.To clarify the effect of subsoiling before winter wheat on the kernel position effect of densely grown summer maize and its regulatory mechanism,field experiments were conducted during the 2020-2021 and 2021-2022 growing seasons using a split-plot design.The main plots included two tillage practices:conventional tillage practice(CT)and subsoiling before the sowing of winter wheat(SS);and the subplots consisted of three plant densities(D1-D3 at 6.0×10~4,7.5×10~4,and 9.0×10~4 plants ha-1).Compared with CT,SS alleviated the kernel position effect by increasing the weight ratio of inferior to superior kernels(WR)in the D2 and D3 treated plants.The higher WR of SS treated plants contributed largely to the improved flling of inferior kernels.Under the same plant density,SS signifcantly improved the root dry matter accumulation(DMA)and antioxidant enzyme activities(superoxide dismutase(SOD)and peroxidase(POD)),and it reduced the malondialdehyde(MDA)content,especially for the plants grown under higher plant densities.These results indicated that SS delayed the root senescence,which is associated with the reduced soil bulk density.In addition,compared with CT,SS increased the leaf chlorophyll content from 20 days after silking to physiological maturity and the post-silking leaf area duration,and it reduced the post-silking leaf chlorophyll reduction rate and leaf area reduction rate,indicating that the post-silking leaf senescence had been alleviated.Under the same plant density,the post-silking DMA of SS was obviously higher than that of CT,which was probably related to the improved leaf area duration and photosynthetic enzyme activities(phosphoenolpyruvate carboxylase(PEPC)and Rubisco).The correlation analysis revealed that the main mechanism of SS in alleviating the kernel position effect of densely grown summer maize is as follows:SS delays the post-silking root-shoot senescence by regulating soil physical properties,and further improves the post-silking DMA and flling of inferior kernels,which ultimately alleviates the kernel position effect and improves grain yield.The results of this study provide new theoretical support for the promotion of summer maize yield by subsoiling before winter wheat.
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.
基金supported by the Project funded by the Natural Science Foundation of Hainan Province(Grant No.322QN248)the National Natural Science Foundation of China(Grant Nos.32401488,32060409,32371782 and 32460358)+3 种基金the Innovational Fund for Scientific and Technological Personnel of Hainan Province(Grant No.KJRC 2023C21)the Hainan High-level Talents Project(Grant No.321RC475)Collaborative Innovation Center Project of Nanfan and High-Efficiency Tropical Agriculture in Hainan University(XTCX2022NYB08)Collaborative Innovation Center Project of Ecological Civilization in Hainan University(XTCX2022STC10).
文摘Improving salt tolerance and mitigating senescence in the presence of high salinity are crucial for sustaining agricultural productivity.Previous research has demonstrated that hydrogen peroxide(H_(2)O_(2)),specifically H_(2)O_(2)derived from roots and mediated by the respiratory burst oxidase homolog(NADPH),plays a significant role in regulating ion and plant hormone homeostasis in glycophytic plants,such as Arabidopsis.However,the extent to which root-derived H_(2)O_(2)fulfils similar functions in halophytic plants remains uncertain.Therefore,our study aimed to explore the potential contribution of root-sourced H_(2)O_(2)in delaying leaf senescence induced by high salinity,utilizing seashore paspalum as a model halophytic plant.The application of the NADPH-oxidase inhibitor DPI,coupled with a series of leaf senescence analyses,we revealed that root-derived H_(2)O_(2)significantly retards salt-induced leaf senescence.Furthermore,through the application of hormone analysis,lipidomics,ionomics,Non-invasive Micro-test Technology(NMT),and transcriptomics,we established that NADPH-dependent H_(2)O_(2)induced by salt stress in the roots was indispensable for maintaining the balance of the aging hormone,jasmonic acid(JA),and sodium ion homeostasis within this halophytic plant.Finally,by utilizing AtrbohD Arabidopsis mutants and virus-induced gene silencing(VIGs)in Paspalum vaginatum,we demonstrated the pivotal role played by root-sourced H_(2)O_(2)in upholding JA homeostasis and regulating JA-triggered leaf senescence in P.vaginatum.This study offers novel insights into the mechanisms that govern plant leaf senescence and its response to salinity-induced stress.
基金supported by the Ministry of Science and Technology of China(2020YFA0908900)National Natural Science Foundation of China(21935011 and 82072490)+1 种基金Shenzhen Science and Technology Innovation Commission(KQTD20200820113012029 and KJZD20230923114612025)Guangdong Provincial Key Laboratory of Advanced Biomaterials(2022B1212010003).
文摘Aging is a pivotal risk factor for intervertebral disc degeneration(IVDD)and chronic low back pain(LBP).The restoration of aging nucleus pulposus cells(NPCs)to a youthful epigenetic state is crucial for IVDD treatment,but remains a formidable challenge.Here,we proposed a strategy to partially reprogram and reinstate youthful epigenetics of senescent NPCs by delivering a plasmid carrier that expressed pluripotency-associated genes(Oct4,Klf4 and Sox2)in Cavin2-modified exosomes(OKS@M-Exo)for treatment of IVDD and alleviating LBP.The functional OKS@M-Exo efficaciously alleviated senescence markers(p16^(INK4a),p21^(CIP1)and p53),reduced DNA damage and H4K20me3 expression,as well as restored proliferation ability and metabolic balance in senescent NPCs,as validated through in vitro experiments.In a rat model of IVDD,OKS@M-Exo maintained intervertebral disc height,nucleus pulposus hydration and tissue structure,effectively ameliorated IVDD via decreasing the senescence markers.Additionally,OKS@MExo reduced nociceptive behavior and downregulated nociception markers,indicating its efficiency in alleviating LBP.The transcriptome sequencing analysis also demonstrated that OKS@M-Exo could decrease the expression of age-related pathways and restore cell proliferation.Collectively,reprogramming by the OKS@M-Exo to restore youthful epigenetics of senescent NPCs may hold promise as a therapeutic platform to treat IVDD.
