Recent reports suggest that aging is not solely a physiological process in living beings;instead, it should be considered a pathological process or disease(Amorim et al., 2022). Consequently, this process involves a w...Recent reports suggest that aging is not solely a physiological process in living beings;instead, it should be considered a pathological process or disease(Amorim et al., 2022). Consequently, this process involves a wide range of factors, spanning from genetic to environmental factors, and even includes the gut microbiome(GM)(Mayer et al., 2022). All these processes coincide at some point in the inflammatory process, oxidative stress, and apoptosis, at different degrees in various organs and systems that constitute a living organism(Mayer et al., 2022;AguilarHernández et al., 2023).展开更多
The neuromuscular junction(NMJ)is an essential synaptic structure composed of motor neurons,skeletal muscles,and glial cells that orchestrate the critical process of muscle contraction(Li et al.,2018).The typical NMJ ...The neuromuscular junction(NMJ)is an essential synaptic structure composed of motor neurons,skeletal muscles,and glial cells that orchestrate the critical process of muscle contraction(Li et al.,2018).The typical NMJ structure is classically described as having a“pretzel-like”shape in mice(Figure 1),whereas human NMJs have a smaller,fragmented structure throughout adulthood.Degenerated NMJs exhibit smaller or fragmented endplates,partial denervation,reduced numbers of synaptic vesicles,abnormal presynaptic mitochondria,and dysfunctional perisynaptic Schwann cells(Alhindi et al.,2022).展开更多
“Last scene of all that ends this strange,eventful history,is second childishness and mere oblivion.I am sans teeth,sans eyes,sans taste,sans everything.”William Shakespeare‘As You Like It'Act 2,Sc.7,l.139Aging...“Last scene of all that ends this strange,eventful history,is second childishness and mere oblivion.I am sans teeth,sans eyes,sans taste,sans everything.”William Shakespeare‘As You Like It'Act 2,Sc.7,l.139Aging of the human brain is characterized by a progressive decline of its functional capacity;this decline however varies widely,and cognitive longevity differs substantially between individuals.展开更多
Regulated cell death(such as apoptosis,necroptosis,pyroptosis,autophagy,cuproptosis,ferroptosis,disulfidptosis)involves complex signaling pathways and molecular effectors,and has been proven to be an important regulat...Regulated cell death(such as apoptosis,necroptosis,pyroptosis,autophagy,cuproptosis,ferroptosis,disulfidptosis)involves complex signaling pathways and molecular effectors,and has been proven to be an important regulatory mechanism for regulating neuronal aging and death.However,excessive activation of regulated cell death may lead to the progression of aging-related diseases.This review summarizes recent advances in the understanding of seven forms of regulated cell death in age-related diseases.Notably,the newly identified ferroptosis and cuproptosis have been implicated in the risk of cognitive impairment and neurodegenerative diseases.These forms of cell death exacerbate disease progression by promoting inflammation,oxidative stress,and pathological protein aggregation.The review also provides an overview of key signaling pathways and crosstalk mechanisms among these regulated cell death forms,with a focus on ferroptosis,cuproptosis,and disulfidptosis.For instance,FDX1 directly induces cuproptosis by regulating copper ion valency and dihydrolipoamide S-acetyltransferase aggregation,while copper mediates glutathione peroxidase 4 degradation,enhancing ferroptosis sensitivity.Additionally,inhibiting the Xc-transport system to prevent ferroptosis can increase disulfide formation and shift the NADP^(+)/NADPH ratio,transitioning ferroptosis to disulfidptosis.These insights help to uncover the potential connections among these novel regulated cell death forms and differentiate them from traditional regulated cell death mechanisms.In conclusion,identifying key targets and their crosstalk points among various regulated cell death pathways may aid in developing specific biomarkers to reverse the aging clock and treat age-related neurodegenerative conditions.展开更多
The complex morphological,anatomical,physiological,and chemical mechanisms within the aging brain have been the hot topic of research for centuries.The aging process alters the brain structure that affects functions a...The complex morphological,anatomical,physiological,and chemical mechanisms within the aging brain have been the hot topic of research for centuries.The aging process alters the brain structure that affects functions and cognitions,but the worsening of such processes contributes to the pathogenesis of neurodegenerative disorders,such as Alzheimer's disease.Beyond these observable,mild morphological shifts,significant functional modifications in neurotransmission and neuronal activity critically influence the aging brain.Understanding these changes is important for maintaining cognitive health,especially given the increasing prevalence of age-related conditions that affect cognition.This review aims to explore the age-induced changes in brain plasticity and molecular processes,differentiating normal aging from the pathogenesis of Alzheimer's disease,thereby providing insights into predicting the risk of dementia,particularly Alzheimer's disease.展开更多
The oral cavity is a complex physiological community encompassing a wide range of microorganisms.Dysbiosis of oral microbiota can lead to various oral infectious diseases,such as periodontitis and tooth decay,and even...The oral cavity is a complex physiological community encompassing a wide range of microorganisms.Dysbiosis of oral microbiota can lead to various oral infectious diseases,such as periodontitis and tooth decay,and even affect systemic health,including brain aging and neurodegenerative diseases.Recent studies have highlighted how oral microbes might be involved in brain aging and neurodegeneration,indicating potential avenues for intervention strategies.In this review,we summarize clinical evidence demonstrating a link between oral microbes/oral infectious diseases and brain aging/neurodegenerative diseases,and dissect potential mechanisms by which oral microbes contribute to brain aging and neurodegeneration.We also highlight advances in therapeutic development grounded in the realm of oral microbes,with the goal of advancing brain health and promoting healthy aging.展开更多
The impact of cryorolling(CR)and room temperature rolling(RTR)followed by artificial aging on the corrosion characteristics of 2195 Al−Li alloy(AA2195)was studied.Transmission electron microscope,scanning electron mic...The impact of cryorolling(CR)and room temperature rolling(RTR)followed by artificial aging on the corrosion characteristics of 2195 Al−Li alloy(AA2195)was studied.Transmission electron microscope,scanning electron microscope,optical microscope,intergranular corrosion experiment,and electrochemical experiment were used.Throughout different stages of aging treatment,the corrosion behavior of both CR and RTR samples exhibited a sequential progression of pitting corrosion,followed by intergranular corrosion,and then pitting corrosion again.The corrosion rates of both samples initially showed an increase,followed by a gradual stabilization over time.The size and density of T1 phase significantly influenced the corrosion performance of the alloy.During the peak aging and over-aging stages,the CR sample exhibited superior corrosion resistance to the RTR sample,attributed to its finer T1 phase.展开更多
With the rapidly aging human population,age-related cognitive decline and dementia are becoming increasingly prevalent worldwide.Aging is considered the main risk factor for cognitive decline and acts through alterati...With the rapidly aging human population,age-related cognitive decline and dementia are becoming increasingly prevalent worldwide.Aging is considered the main risk factor for cognitive decline and acts through alterations in the composition of the gut microbiota,microbial metabolites,and the functions of astrocytes.The microbiota–gut–brain axis has been the focus of multiple studies and is closely associated with cognitive function.This article provides a comprehensive review of the specific changes that occur in the composition of the gut microbiota and microbial metabolites in older individuals and discusses how the aging of astrocytes and reactive astrocytosis are closely related to age-related cognitive decline and neurodegenerative diseases.This article also summarizes the gut microbiota components that affect astrocyte function,mainly through the vagus nerve,immune responses,circadian rhythms,and microbial metabolites.Finally,this article summarizes the mechanism by which the gut microbiota–astrocyte axis plays a role in Alzheimer’s and Parkinson’s diseases.Our findings have revealed the critical role of the microbiota–astrocyte axis in age-related cognitive decline,aiding in a deeper understanding of potential gut microbiome-based adjuvant therapy strategies for this condition.展开更多
Retinal aging has been recognized as a significant risk factor for various retinal disorders,including diabetic retinopathy,age-related macular degeneration,and glaucoma,following a growing understanding of the molecu...Retinal aging has been recognized as a significant risk factor for various retinal disorders,including diabetic retinopathy,age-related macular degeneration,and glaucoma,following a growing understanding of the molecular underpinnings of their development.This comprehensive review explores the mechanisms of retinal aging and investigates potential neuroprotective approaches,focusing on the activation of transcription factor EB.Recent meta-analyses have demonstrated promising outcomes of transcription factor EB-targeted strategies,such as exercise,calorie restriction,rapamycin,and metformin,in patients and animal models of these common retinal diseases.The review critically assesses the role of transcription factor EB in retinal biology during aging,its neuroprotective effects,and its therapeutic potential for retinal disorders.The impact of transcription factor EB on retinal aging is cell-specific,influencing metabolic reprogramming and energy homeostasis in retinal neurons through the regulation of mitochondrial quality control and nutrient-sensing pathways.In vascular endothelial cells,transcription factor EB controls important processes,including endothelial cell proliferation,endothelial tube formation,and nitric oxide levels,thereby influencing the inner blood-retinal barrier,angiogenesis,and retinal microvasculature.Additionally,transcription factor EB affects vascular smooth muscle cells,inhibiting vascular calcification and atherogenesis.In retinal pigment epithelial cells,transcription factor EB modulates functions such as autophagy,lysosomal dynamics,and clearance of the aging pigment lipofuscin,thereby promoting photoreceptor survival and regulating vascular endothelial growth factor A expression involved in neovascularization.These cell-specific functions of transcription factor EB significantly impact retinal aging mechanisms encompassing proteostasis,neuronal synapse plasticity,energy metabolism,microvasculature,and inflammation,ultimately offering protection against retinal aging and diseases.The review emphasizes transcription factor EB as a potential therapeutic target for retinal diseases.Therefore,it is imperative to obtain well-controlled direct experimental evidence to confirm the efficacy of transcription factor EB modulation in retinal diseases while minimizing its risk of adverse effects.展开更多
Seed aging tolerance during storage is generally an important trait for crop production, yet the role of small auxin-up RNA genes in conferring seed aging tolerance is largely unknown in rice. In this study, one small...Seed aging tolerance during storage is generally an important trait for crop production, yet the role of small auxin-up RNA genes in conferring seed aging tolerance is largely unknown in rice. In this study, one small auxin-up RNA gene, OsSAUR33, was found to be involved in the regulation of seed aging tolerance in rice. The expression of OsSAUR33 was significantly induced in aged seeds compared with unaged seeds during the seed germination phase. Accordingly, the disruption of OsSAUR33 significantly reduced seed vigor compared to the wild type(WT) in response to natural storage or artificial aging treatments. The rice OsSAUR33 gene promotes the vigor of aged seeds by enhancing their reactive oxygen species(ROS) level during seed germination, and the accumulation of ROS was significantly delayed in the aged seeds of Ossaur33 mutants in comparison with WT during seed germination. Hydrogen peroxide(H_(2)O_(2)) treatments promoted the vigor of aged seeds in various rice varieties. Our results provide timely theoretical and technical insights for the trait improvement of seed aging tolerance in rice.展开更多
Although the plastic loading can enhance creep deformation and yield strength,the anisotropic Stress Relaxation Aging(SRA)behavior and mechanism under plastic loading remain unclear,which presents a significant challe...Although the plastic loading can enhance creep deformation and yield strength,the anisotropic Stress Relaxation Aging(SRA)behavior and mechanism under plastic loading remain unclear,which presents a significant challenge in accurately shaping aluminum alloy panels.In this study,the SRA behavior of 2195-T4 Al-Cu-Li alloys were thoroughly studied under initial loading stresses within the elastic(210/250 MPa)and plastic(380/420 MPa)ranges at 180℃by stress relaxation and tensile tests as well as microstructure characterization.The findings reveal that compared with those under elastic loadings,in-plane anisotropy(IPA)values of the stress relaxation amount,yield strength and fracture elongation under plastic loadings are reduced by 60%–80%,70%–90% and 72%–89%,respectively.Similarly,IPA values of precipitate size in grains and PrecipitationFree Zones(PFZ)width at grain boundaries under plastic loading decrease by 31.4%and 94.4%respectively.These results indicate plastic loading significantly weakens the anisotropic SRA behavior,owing to numerous uniformly distributed fine T1phases and small IPA values of both T1precipitates size and PFZ width in various loading directions.Compared with those of elastic loadingaged alloys,yield strength of plastic loading-aged alloys shows high strength-ductility because of the combined effect of closely dispersed fine T1precipitates,narrowed PFZ and numerous sheared and rotated T1phases at different locations during tensile process.The uniformly distributed larger Kernel Average Misorientation(KAM)and Schmidt factor values of the plastic loading-aged alloy,as well as the cross-slip generated,also help to enhance the strength and ductility of the alloy.展开更多
基金funded by CONAHCYT grant(252808)to GFCONAHCYT’s“Estancias Posdoctorales por México”program(662350)to HTB。
文摘Recent reports suggest that aging is not solely a physiological process in living beings;instead, it should be considered a pathological process or disease(Amorim et al., 2022). Consequently, this process involves a wide range of factors, spanning from genetic to environmental factors, and even includes the gut microbiome(GM)(Mayer et al., 2022). All these processes coincide at some point in the inflammatory process, oxidative stress, and apoptosis, at different degrees in various organs and systems that constitute a living organism(Mayer et al., 2022;AguilarHernández et al., 2023).
基金funded by the Japan Society for the Promotion of Science,JSPS,23K07290(to MF).
文摘The neuromuscular junction(NMJ)is an essential synaptic structure composed of motor neurons,skeletal muscles,and glial cells that orchestrate the critical process of muscle contraction(Li et al.,2018).The typical NMJ structure is classically described as having a“pretzel-like”shape in mice(Figure 1),whereas human NMJs have a smaller,fragmented structure throughout adulthood.Degenerated NMJs exhibit smaller or fragmented endplates,partial denervation,reduced numbers of synaptic vesicles,abnormal presynaptic mitochondria,and dysfunctional perisynaptic Schwann cells(Alhindi et al.,2022).
文摘“Last scene of all that ends this strange,eventful history,is second childishness and mere oblivion.I am sans teeth,sans eyes,sans taste,sans everything.”William Shakespeare‘As You Like It'Act 2,Sc.7,l.139Aging of the human brain is characterized by a progressive decline of its functional capacity;this decline however varies widely,and cognitive longevity differs substantially between individuals.
基金supported by the Key Projects of Medical Science and Technology of Henan Province,No.SBGJ202002099(to JY)。
文摘Regulated cell death(such as apoptosis,necroptosis,pyroptosis,autophagy,cuproptosis,ferroptosis,disulfidptosis)involves complex signaling pathways and molecular effectors,and has been proven to be an important regulatory mechanism for regulating neuronal aging and death.However,excessive activation of regulated cell death may lead to the progression of aging-related diseases.This review summarizes recent advances in the understanding of seven forms of regulated cell death in age-related diseases.Notably,the newly identified ferroptosis and cuproptosis have been implicated in the risk of cognitive impairment and neurodegenerative diseases.These forms of cell death exacerbate disease progression by promoting inflammation,oxidative stress,and pathological protein aggregation.The review also provides an overview of key signaling pathways and crosstalk mechanisms among these regulated cell death forms,with a focus on ferroptosis,cuproptosis,and disulfidptosis.For instance,FDX1 directly induces cuproptosis by regulating copper ion valency and dihydrolipoamide S-acetyltransferase aggregation,while copper mediates glutathione peroxidase 4 degradation,enhancing ferroptosis sensitivity.Additionally,inhibiting the Xc-transport system to prevent ferroptosis can increase disulfide formation and shift the NADP^(+)/NADPH ratio,transitioning ferroptosis to disulfidptosis.These insights help to uncover the potential connections among these novel regulated cell death forms and differentiate them from traditional regulated cell death mechanisms.In conclusion,identifying key targets and their crosstalk points among various regulated cell death pathways may aid in developing specific biomarkers to reverse the aging clock and treat age-related neurodegenerative conditions.
文摘The complex morphological,anatomical,physiological,and chemical mechanisms within the aging brain have been the hot topic of research for centuries.The aging process alters the brain structure that affects functions and cognitions,but the worsening of such processes contributes to the pathogenesis of neurodegenerative disorders,such as Alzheimer's disease.Beyond these observable,mild morphological shifts,significant functional modifications in neurotransmission and neuronal activity critically influence the aging brain.Understanding these changes is important for maintaining cognitive health,especially given the increasing prevalence of age-related conditions that affect cognition.This review aims to explore the age-induced changes in brain plasticity and molecular processes,differentiating normal aging from the pathogenesis of Alzheimer's disease,thereby providing insights into predicting the risk of dementia,particularly Alzheimer's disease.
基金supported by the National Natural Science Foundation of China,No.81921006(to GHL)。
文摘The oral cavity is a complex physiological community encompassing a wide range of microorganisms.Dysbiosis of oral microbiota can lead to various oral infectious diseases,such as periodontitis and tooth decay,and even affect systemic health,including brain aging and neurodegenerative diseases.Recent studies have highlighted how oral microbes might be involved in brain aging and neurodegeneration,indicating potential avenues for intervention strategies.In this review,we summarize clinical evidence demonstrating a link between oral microbes/oral infectious diseases and brain aging/neurodegenerative diseases,and dissect potential mechanisms by which oral microbes contribute to brain aging and neurodegeneration.We also highlight advances in therapeutic development grounded in the realm of oral microbes,with the goal of advancing brain health and promoting healthy aging.
基金supported by the High-tech Industry Technology Innovation Leading Plan of Hunan Province,China(No.2022GK4032)the State Key Laboratory of Precision Manufacturing for Extreme Service Performance at Central South University,China.
文摘The impact of cryorolling(CR)and room temperature rolling(RTR)followed by artificial aging on the corrosion characteristics of 2195 Al−Li alloy(AA2195)was studied.Transmission electron microscope,scanning electron microscope,optical microscope,intergranular corrosion experiment,and electrochemical experiment were used.Throughout different stages of aging treatment,the corrosion behavior of both CR and RTR samples exhibited a sequential progression of pitting corrosion,followed by intergranular corrosion,and then pitting corrosion again.The corrosion rates of both samples initially showed an increase,followed by a gradual stabilization over time.The size and density of T1 phase significantly influenced the corrosion performance of the alloy.During the peak aging and over-aging stages,the CR sample exhibited superior corrosion resistance to the RTR sample,attributed to its finer T1 phase.
基金supported by the Haihe Laboratory of Cell Ecosystem Innovation Foundation,No.22HHXBSS00047(to PL)Graduate Science and Technology Innovation Project of Tianjin,No.2022BKY173(to LZ)Tianjin Municipal Science and Technology Bureau Foundation,No.20201194(to PL).
文摘With the rapidly aging human population,age-related cognitive decline and dementia are becoming increasingly prevalent worldwide.Aging is considered the main risk factor for cognitive decline and acts through alterations in the composition of the gut microbiota,microbial metabolites,and the functions of astrocytes.The microbiota–gut–brain axis has been the focus of multiple studies and is closely associated with cognitive function.This article provides a comprehensive review of the specific changes that occur in the composition of the gut microbiota and microbial metabolites in older individuals and discusses how the aging of astrocytes and reactive astrocytosis are closely related to age-related cognitive decline and neurodegenerative diseases.This article also summarizes the gut microbiota components that affect astrocyte function,mainly through the vagus nerve,immune responses,circadian rhythms,and microbial metabolites.Finally,this article summarizes the mechanism by which the gut microbiota–astrocyte axis plays a role in Alzheimer’s and Parkinson’s diseases.Our findings have revealed the critical role of the microbiota–astrocyte axis in age-related cognitive decline,aiding in a deeper understanding of potential gut microbiome-based adjuvant therapy strategies for this condition.
基金supported by the Start-up Fund for new faculty from the Hong Kong Polytechnic University(PolyU)(A0043215)(to SA)the General Research Fund and Research Impact Fund from the Hong Kong Research Grants Council(15106018,R5032-18)(to DYT)+1 种基金the Research Center for SHARP Vision in PolyU(P0045843)(to SA)the InnoHK scheme from the Hong Kong Special Administrative Region Government(to DYT).
文摘Retinal aging has been recognized as a significant risk factor for various retinal disorders,including diabetic retinopathy,age-related macular degeneration,and glaucoma,following a growing understanding of the molecular underpinnings of their development.This comprehensive review explores the mechanisms of retinal aging and investigates potential neuroprotective approaches,focusing on the activation of transcription factor EB.Recent meta-analyses have demonstrated promising outcomes of transcription factor EB-targeted strategies,such as exercise,calorie restriction,rapamycin,and metformin,in patients and animal models of these common retinal diseases.The review critically assesses the role of transcription factor EB in retinal biology during aging,its neuroprotective effects,and its therapeutic potential for retinal disorders.The impact of transcription factor EB on retinal aging is cell-specific,influencing metabolic reprogramming and energy homeostasis in retinal neurons through the regulation of mitochondrial quality control and nutrient-sensing pathways.In vascular endothelial cells,transcription factor EB controls important processes,including endothelial cell proliferation,endothelial tube formation,and nitric oxide levels,thereby influencing the inner blood-retinal barrier,angiogenesis,and retinal microvasculature.Additionally,transcription factor EB affects vascular smooth muscle cells,inhibiting vascular calcification and atherogenesis.In retinal pigment epithelial cells,transcription factor EB modulates functions such as autophagy,lysosomal dynamics,and clearance of the aging pigment lipofuscin,thereby promoting photoreceptor survival and regulating vascular endothelial growth factor A expression involved in neovascularization.These cell-specific functions of transcription factor EB significantly impact retinal aging mechanisms encompassing proteostasis,neuronal synapse plasticity,energy metabolism,microvasculature,and inflammation,ultimately offering protection against retinal aging and diseases.The review emphasizes transcription factor EB as a potential therapeutic target for retinal diseases.Therefore,it is imperative to obtain well-controlled direct experimental evidence to confirm the efficacy of transcription factor EB modulation in retinal diseases while minimizing its risk of adverse effects.
基金supported by the Key-Area Research and Development Program of Guangdong Province,China(2022B0202060006)the National Natural Science Foundation of China(32201838,32272157,32172052,and 31971995)+2 种基金the Natural Science Foundation of Guangdong Province,China(2023A1515012052)the Project of Sanya Yazhou Bay Science and Technology City,China(SCKJJYRC-2022-87)the Double First-class Discipline Promotion Project,China(2021B10564001)
文摘Seed aging tolerance during storage is generally an important trait for crop production, yet the role of small auxin-up RNA genes in conferring seed aging tolerance is largely unknown in rice. In this study, one small auxin-up RNA gene, OsSAUR33, was found to be involved in the regulation of seed aging tolerance in rice. The expression of OsSAUR33 was significantly induced in aged seeds compared with unaged seeds during the seed germination phase. Accordingly, the disruption of OsSAUR33 significantly reduced seed vigor compared to the wild type(WT) in response to natural storage or artificial aging treatments. The rice OsSAUR33 gene promotes the vigor of aged seeds by enhancing their reactive oxygen species(ROS) level during seed germination, and the accumulation of ROS was significantly delayed in the aged seeds of Ossaur33 mutants in comparison with WT during seed germination. Hydrogen peroxide(H_(2)O_(2)) treatments promoted the vigor of aged seeds in various rice varieties. Our results provide timely theoretical and technical insights for the trait improvement of seed aging tolerance in rice.
基金support from the Key Program of the National Natural Science Foundation of China(No.51235010)。
文摘Although the plastic loading can enhance creep deformation and yield strength,the anisotropic Stress Relaxation Aging(SRA)behavior and mechanism under plastic loading remain unclear,which presents a significant challenge in accurately shaping aluminum alloy panels.In this study,the SRA behavior of 2195-T4 Al-Cu-Li alloys were thoroughly studied under initial loading stresses within the elastic(210/250 MPa)and plastic(380/420 MPa)ranges at 180℃by stress relaxation and tensile tests as well as microstructure characterization.The findings reveal that compared with those under elastic loadings,in-plane anisotropy(IPA)values of the stress relaxation amount,yield strength and fracture elongation under plastic loadings are reduced by 60%–80%,70%–90% and 72%–89%,respectively.Similarly,IPA values of precipitate size in grains and PrecipitationFree Zones(PFZ)width at grain boundaries under plastic loading decrease by 31.4%and 94.4%respectively.These results indicate plastic loading significantly weakens the anisotropic SRA behavior,owing to numerous uniformly distributed fine T1phases and small IPA values of both T1precipitates size and PFZ width in various loading directions.Compared with those of elastic loadingaged alloys,yield strength of plastic loading-aged alloys shows high strength-ductility because of the combined effect of closely dispersed fine T1precipitates,narrowed PFZ and numerous sheared and rotated T1phases at different locations during tensile process.The uniformly distributed larger Kernel Average Misorientation(KAM)and Schmidt factor values of the plastic loading-aged alloy,as well as the cross-slip generated,also help to enhance the strength and ductility of the alloy.
