Aging,mitochondria,and neurodegenerative diseases:Aging is often viewed as the buildup of changes that lead to the gradual transformations associated with getting older,along with a rising likelihood of disease and mo...Aging,mitochondria,and neurodegenerative diseases:Aging is often viewed as the buildup of changes that lead to the gradual transformations associated with getting older,along with a rising likelihood of disease and mortality.Although organis m-wide deterioration is observed during aging,organs with high metabolic demand,such as the brain,are more vulnerable.展开更多
Regenerative medicine is a promising therapeutic avenue for previously incurable diseases.As the risk of chronic and degenerative diseases significantly increases with age,the elderly population represents a major coh...Regenerative medicine is a promising therapeutic avenue for previously incurable diseases.As the risk of chronic and degenerative diseases significantly increases with age,the elderly population represents a major cohort for stem cell-based therapies.However,the regenerative potential of stem cells significantly decreases with advanced age and deteriorating health status of the donor.Therefore,the efficacy of autologous stem cell therapy is significantly compromised in older patients.To overcome these limitations,alternative strategies have been used to restore the age-and disease-depleted function of stem cells.These methods aim to restore the therapeutic efficacy of aged stem cells for autologous use.This article explores the effect of donor age and health status on the regenerative potential of stem cells.It further highlights the limitations of stem cell-based therapy for autologous treatment in the elderly.A comprehensive insight into the potential strategies to address the“age”and“disease”compromised regenerative potential of autologous stem cells is also presented.The information provided here serves as a valuable resource for physicians and patients for optimization of stem cellbased autologous therapy for aged patients.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
The study evaluated the skin anti-aging activity of Astragalus sarcocolla leaves extract(ASE)by assessing its antioxidant and inhibitory effect activity on matrix metalloproteinase(MMP),collagenase,elastase,hyaluronid...The study evaluated the skin anti-aging activity of Astragalus sarcocolla leaves extract(ASE)by assessing its antioxidant and inhibitory effect activity on matrix metalloproteinase(MMP),collagenase,elastase,hyaluronidase,and tyrosinase in relation to its chemical composition.Ultra Performance Liquid Chromatography-Mass Spectrometry(UPLC-MS)identified 27 metabolites(15 flavonoids,8 phenolic acids and their derivatives,and 4 coumarins).ASE showed strong antioxidant capacity in DPPH(IC_(50)value of 26.05μg/mL)and FRAP(2433μM FeSO_(4)/g extract)assays.The extract inhibited MMP-1 and MMP-9 in a concentration-dependent manner and suppressed collagenase,elastase,hyaluronidase,and tyrosinase activities(IC_(50)=35.038,40.748,61.389,and 30.980μg/mL,respectively).A network pharmacology study was conducted to uncover the mechanisms responsible for skin anti-aging effects,and molecular docking further evaluated interactions of key metabolites with hub targets.Twenty-one bioactive metabolites,selected based on oral bioavailability and drug-likeness,highlighted cinnamic acid,acacetin,luteolin,kaempferol,and apigenin as key compounds.MMP-9,ESR1,PTGS-2,and EGFR were identified as main targets.Docking studies revealed that acacetin and apigenin have stronger binding affinities to MMP-9,PTGS-2,and EGFR than other constituents.These findings suggest that ASE may serve as a natural multi-target skin anti-aging remedy with potential cosmetic applications.展开更多
Objectives This study aimed to explore the lagged and cumulative effects of risk factors on disability in older adults using distributed lag non-linear models(DLNMs).Methods We utilized data from the China Health and ...Objectives This study aimed to explore the lagged and cumulative effects of risk factors on disability in older adults using distributed lag non-linear models(DLNMs).Methods We utilized data from the China Health and Retirement Longitudinal Study(CHARLS).After feature selection via Elastic Net Regularization,we applied DLNMs to evaluate the lagged effects of risk factors.Disability was defined as the presence of any difficulties in basic activities of daily living(BADL).The cumulative relative risk(CRR)was calculated by summing the lag-specific risk estimates,representing the cumulative disability risk over the specified lag period.Effect modifications and sensitivity analyses were also performed.Results This study included a total of 2,318 participants.Early-phase lag factors,such as the difficulty in stooping(CRR=3.58;95%CI:2.31-5.55;P<0.001)and walking(CRR=2.77;95%CI:1.39-5.55;P<0.001),exerted the strongest effects immediately upon occurrence.Mid-phase lag factors,such as arthritis(CRR=1.51;95%CI:1.10-2.06;P=0.001),showed a resurgence in disability risk within 2-3 years.Late-phase lag factors,including depressive symptoms(CRR=2.38;95%CI:1.30-4.35;P<0.001)and elevated systolic blood pressure(CRR=1.64;95%CI:1.06-2.79;P=0.02),exhibited significant long-term cumulative risks.Conversely,grip strength(CRR=0.80;95%CI:0.54-0.95;P=0.02)and social participation(CRR=0.89;95%CI:0.73-0.99;P=0.04)were significant protective factors.Conclusions The findings underscore the importance of tailored interventions that account for various lag characteristics of different factors to effectively mitigate disability risk.Future studies should explore the underlying biological and sociological mechanisms of these lagged effects,identify intervention strategies that target risk factors with different lagged patterns,and evaluate their effectiveness.展开更多
Fe-Ga-based alloys are considered promising magnetostrictive candidates because of their high permeability and favorable mechanical properties.However,currently developed Fe-Ga-based alloys often suffer from a limited...Fe-Ga-based alloys are considered promising magnetostrictive candidates because of their high permeability and favorable mechanical properties.However,currently developed Fe-Ga-based alloys often suffer from a limited capability for microstructure manipulation,which restricts their magnetostrictive performance.To address this limitation,this study proposes a novel strategy combining laser-beam powder bed fusion(LPBF)and aging treatment to modulate the microstructure and enhance magnetostrictive properties of Fe-Ga-B alloys.Considering the positive influence of B element on magnetostrictive property and ductility,B-doped magnetostrictive Fe-Ga alloys were prepared via the LPBF process and then aged at 600℃for varying times(1,2,and 3 h,respectively).The LPBF process,characterized by high thermal gradients and rapid solidification,produced a microstructure featuring<001>oriented grains and sparse m-D0_(3)nanoprecipitates embedded in an A2 matrix.After the aging treatment,sufficient nucleation and growth of nanoprecipitates were enhanced.Specifically,the sample aged for 2 h developed a high density of larger m-D0_(3)nanoprecipitates.This optimized microstructure yielded a high magnetostrictive strain of(109±12)ppm and a substantially reduced saturation field—decreased by~49.1%compared to the as-fabricated state—primarily due to the synergistic effect of the<001>texture and the dense nanoprecipitates.Moreover,all the prepared alloys exhibited good soft-magnetic characteristics and comparable mechanical properties.Therefore,the combination of LPBF and aging treatment offers a promising route for tailoring the macro/microstructure and performance of magnetostrictive Fe-Ga alloys for diverse applications.展开更多
Aging plays a critical role in determining the durability and long-term performance of asphalt pavements,as it is influenced by both external factors(e.g.,temperature,ultraviolet(UV)radiation,moisture,oxidative gases)...Aging plays a critical role in determining the durability and long-term performance of asphalt pavements,as it is influenced by both external factors(e.g.,temperature,ultraviolet(UV)radiation,moisture,oxidative gases)and internal factors such as binder composition.Although laboratory simulations of aging are well established for conventional bituminous binders,limited attention has been paid to replicating and evaluating aging processes in bio-based binders.This review provides a comprehensive analysis of current laboratory techniques for simulating and assessing binder aging,with a focus on two key areas:aging simulation protocols and evaluation methodologies.The analysis shows that although several efforts have been made to incorporate external aging factors into lab simulations,significant challenges persist,especially in the case of bio-based binders,which are characterized by a high variability in composition and limited understanding of their aging behavior.Current evaluation approaches also exhibit limitations.Improvements are needed in the molecular-level analysis of oxidation(e.g.,through more representative oxidation modelsin molecular dynamicssimulations),in the separation and quantification of binder constituents,and in the application of advanced techniques such as fluorescence microscopy to better characterize polymer dispersion.To enhance the reliability of laboratory simulations,future research should aim to improve the correlation between laboratory and field aging,define robust aging indexes,and refine characterization methods.These advancements are particularly critical for bio-based binders,whose performance is highly sensitive to aging and for which standard test protocols are still underdeveloped.A deeper understanding of aging mechanisms in both polymer-modified and biobased binders,along with improved analytical tools for assessing oxidative degradation and morphological changes,will be essential to support the development of sustainable,high-performance paving materials.展开更多
Persistent postsurgical pain is a major clinical concern,especially in the aging population,who represent a growing proportion of surgical patients.Although age is a known pain risk factor,the mechanisms driving age-r...Persistent postsurgical pain is a major clinical concern,especially in the aging population,who represent a growing proportion of surgical patients.Although age is a known pain risk factor,the mechanisms driving age-related vulnerability to chronic postoperative pain remain poorly understood.This study aims to investigate how aging influences the resolution of postoperative pain and to elucidate the roles of microglial activation and synaptic remodeling in the spinal dorsal horn.A plantar incision model in young(3-month-old)and aged(18-month-old)male and female mice was used to mimic postoperative pain conditions.Mechanical and thermal hypersensitivity at various postoperative intervals were assessed by von Frey and Hargreaves tests.Microglial activation and inhibitory/excitatory synaptic densities in the spinal dorsal horn were evaluated using immunofluorescence and 3D reconstruction with Imaris software.On postoperative day(POD)3,both age groups exhibited reduced pain thresholds on the ipsilateral side,along with microglial activation in the dorsal horn.On POD 7,pain thresholds in young mice had returned to baseline with no significant microglial activation,while aged mice showed sustained reduction in pain thresholds,continuous microglial activation,and significant loss of inhibitory synapses without detectable changes in excitatory synapse density.These findings are consistent across both sexes,with no sex-related differences.Collectively,these results suggest that aging is associated with persistent postoperative pain,which correlates with microglial activation and inhibitory synapse loss.These insights advance our understanding of age-related pain vulnerability and may inform the development of more effective,targeted,and age-specific therapeutic strategies to prevent or alleviate persistent postoperative pain in elderly patients.展开更多
文摘Aging,mitochondria,and neurodegenerative diseases:Aging is often viewed as the buildup of changes that lead to the gradual transformations associated with getting older,along with a rising likelihood of disease and mortality.Although organis m-wide deterioration is observed during aging,organs with high metabolic demand,such as the brain,are more vulnerable.
文摘Regenerative medicine is a promising therapeutic avenue for previously incurable diseases.As the risk of chronic and degenerative diseases significantly increases with age,the elderly population represents a major cohort for stem cell-based therapies.However,the regenerative potential of stem cells significantly decreases with advanced age and deteriorating health status of the donor.Therefore,the efficacy of autologous stem cell therapy is significantly compromised in older patients.To overcome these limitations,alternative strategies have been used to restore the age-and disease-depleted function of stem cells.These methods aim to restore the therapeutic efficacy of aged stem cells for autologous use.This article explores the effect of donor age and health status on the regenerative potential of stem cells.It further highlights the limitations of stem cell-based therapy for autologous treatment in the elderly.A comprehensive insight into the potential strategies to address the“age”and“disease”compromised regenerative potential of autologous stem cells is also presented.The information provided here serves as a valuable resource for physicians and patients for optimization of stem cellbased autologous therapy for aged patients.
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funded by the Deanship of Graduate Studies and Scientific Research at Jouf University under grant No.(DGSSR-2023-01-02126).
文摘The study evaluated the skin anti-aging activity of Astragalus sarcocolla leaves extract(ASE)by assessing its antioxidant and inhibitory effect activity on matrix metalloproteinase(MMP),collagenase,elastase,hyaluronidase,and tyrosinase in relation to its chemical composition.Ultra Performance Liquid Chromatography-Mass Spectrometry(UPLC-MS)identified 27 metabolites(15 flavonoids,8 phenolic acids and their derivatives,and 4 coumarins).ASE showed strong antioxidant capacity in DPPH(IC_(50)value of 26.05μg/mL)and FRAP(2433μM FeSO_(4)/g extract)assays.The extract inhibited MMP-1 and MMP-9 in a concentration-dependent manner and suppressed collagenase,elastase,hyaluronidase,and tyrosinase activities(IC_(50)=35.038,40.748,61.389,and 30.980μg/mL,respectively).A network pharmacology study was conducted to uncover the mechanisms responsible for skin anti-aging effects,and molecular docking further evaluated interactions of key metabolites with hub targets.Twenty-one bioactive metabolites,selected based on oral bioavailability and drug-likeness,highlighted cinnamic acid,acacetin,luteolin,kaempferol,and apigenin as key compounds.MMP-9,ESR1,PTGS-2,and EGFR were identified as main targets.Docking studies revealed that acacetin and apigenin have stronger binding affinities to MMP-9,PTGS-2,and EGFR than other constituents.These findings suggest that ASE may serve as a natural multi-target skin anti-aging remedy with potential cosmetic applications.
基金supported by ScientificResearch Fund of National Health Commission of the People’s Republic of China-Major Science and Technology Program for Medicine and Health in Zhejiang Province(WKJ-ZJ-2406).
文摘Objectives This study aimed to explore the lagged and cumulative effects of risk factors on disability in older adults using distributed lag non-linear models(DLNMs).Methods We utilized data from the China Health and Retirement Longitudinal Study(CHARLS).After feature selection via Elastic Net Regularization,we applied DLNMs to evaluate the lagged effects of risk factors.Disability was defined as the presence of any difficulties in basic activities of daily living(BADL).The cumulative relative risk(CRR)was calculated by summing the lag-specific risk estimates,representing the cumulative disability risk over the specified lag period.Effect modifications and sensitivity analyses were also performed.Results This study included a total of 2,318 participants.Early-phase lag factors,such as the difficulty in stooping(CRR=3.58;95%CI:2.31-5.55;P<0.001)and walking(CRR=2.77;95%CI:1.39-5.55;P<0.001),exerted the strongest effects immediately upon occurrence.Mid-phase lag factors,such as arthritis(CRR=1.51;95%CI:1.10-2.06;P=0.001),showed a resurgence in disability risk within 2-3 years.Late-phase lag factors,including depressive symptoms(CRR=2.38;95%CI:1.30-4.35;P<0.001)and elevated systolic blood pressure(CRR=1.64;95%CI:1.06-2.79;P=0.02),exhibited significant long-term cumulative risks.Conversely,grip strength(CRR=0.80;95%CI:0.54-0.95;P=0.02)and social participation(CRR=0.89;95%CI:0.73-0.99;P=0.04)were significant protective factors.Conclusions The findings underscore the importance of tailored interventions that account for various lag characteristics of different factors to effectively mitigate disability risk.Future studies should explore the underlying biological and sociological mechanisms of these lagged effects,identify intervention strategies that target risk factors with different lagged patterns,and evaluate their effectiveness.
基金supported by the Hunan Provincial Natural Science Foundation of China(Grant No.2025JJ30015)the National Natural Science Foundation of China(Grant Nos.52571276,52275395,U24A20120,52475362)+4 种基金the Science and Technology Innovation Program of Hunan Province(Grant No.2023RC3046)the National Key Research and Development Program of China(Grant No.2023YFB4605800)the Central South University Innovation-driven Research Programme(Grant No.2023CXQD023)the Jiangxi Provincial Natural Science Foundation of China(Grant No.20224ACB204013)the Project of State Key Laboratory of Precision Manufacturing for Extreme Service Performance of Central South University and the Fundamental Research Funds for the Central Universities of Central South University(Grant No.1053320230182)。
文摘Fe-Ga-based alloys are considered promising magnetostrictive candidates because of their high permeability and favorable mechanical properties.However,currently developed Fe-Ga-based alloys often suffer from a limited capability for microstructure manipulation,which restricts their magnetostrictive performance.To address this limitation,this study proposes a novel strategy combining laser-beam powder bed fusion(LPBF)and aging treatment to modulate the microstructure and enhance magnetostrictive properties of Fe-Ga-B alloys.Considering the positive influence of B element on magnetostrictive property and ductility,B-doped magnetostrictive Fe-Ga alloys were prepared via the LPBF process and then aged at 600℃for varying times(1,2,and 3 h,respectively).The LPBF process,characterized by high thermal gradients and rapid solidification,produced a microstructure featuring<001>oriented grains and sparse m-D0_(3)nanoprecipitates embedded in an A2 matrix.After the aging treatment,sufficient nucleation and growth of nanoprecipitates were enhanced.Specifically,the sample aged for 2 h developed a high density of larger m-D0_(3)nanoprecipitates.This optimized microstructure yielded a high magnetostrictive strain of(109±12)ppm and a substantially reduced saturation field—decreased by~49.1%compared to the as-fabricated state—primarily due to the synergistic effect of the<001>texture and the dense nanoprecipitates.Moreover,all the prepared alloys exhibited good soft-magnetic characteristics and comparable mechanical properties.Therefore,the combination of LPBF and aging treatment offers a promising route for tailoring the macro/microstructure and performance of magnetostrictive Fe-Ga alloys for diverse applications.
文摘Aging plays a critical role in determining the durability and long-term performance of asphalt pavements,as it is influenced by both external factors(e.g.,temperature,ultraviolet(UV)radiation,moisture,oxidative gases)and internal factors such as binder composition.Although laboratory simulations of aging are well established for conventional bituminous binders,limited attention has been paid to replicating and evaluating aging processes in bio-based binders.This review provides a comprehensive analysis of current laboratory techniques for simulating and assessing binder aging,with a focus on two key areas:aging simulation protocols and evaluation methodologies.The analysis shows that although several efforts have been made to incorporate external aging factors into lab simulations,significant challenges persist,especially in the case of bio-based binders,which are characterized by a high variability in composition and limited understanding of their aging behavior.Current evaluation approaches also exhibit limitations.Improvements are needed in the molecular-level analysis of oxidation(e.g.,through more representative oxidation modelsin molecular dynamicssimulations),in the separation and quantification of binder constituents,and in the application of advanced techniques such as fluorescence microscopy to better characterize polymer dispersion.To enhance the reliability of laboratory simulations,future research should aim to improve the correlation between laboratory and field aging,define robust aging indexes,and refine characterization methods.These advancements are particularly critical for bio-based binders,whose performance is highly sensitive to aging and for which standard test protocols are still underdeveloped.A deeper understanding of aging mechanisms in both polymer-modified and biobased binders,along with improved analytical tools for assessing oxidative degradation and morphological changes,will be essential to support the development of sustainable,high-performance paving materials.
基金supported by the National Natural Science Foundation of China(No.82401445 and 82271249)the China Postdoctoral Science Foundation(No.2024M752251)+3 种基金the Postdoctoral Fellowship Program of CPSF(No.GZC20241141)the Sichuan Science and Technology Program(No.2024NSFSC1636 and 2025ZNSFSC1645)the Postdoctoral Research Fund of West China Hospital of Sichuan University(No.2024HXBH013)1-3-5 Project for Disciplines of Excellence of West China Hospital of Sichuan University(No.ZYYC23002)。
文摘Persistent postsurgical pain is a major clinical concern,especially in the aging population,who represent a growing proportion of surgical patients.Although age is a known pain risk factor,the mechanisms driving age-related vulnerability to chronic postoperative pain remain poorly understood.This study aims to investigate how aging influences the resolution of postoperative pain and to elucidate the roles of microglial activation and synaptic remodeling in the spinal dorsal horn.A plantar incision model in young(3-month-old)and aged(18-month-old)male and female mice was used to mimic postoperative pain conditions.Mechanical and thermal hypersensitivity at various postoperative intervals were assessed by von Frey and Hargreaves tests.Microglial activation and inhibitory/excitatory synaptic densities in the spinal dorsal horn were evaluated using immunofluorescence and 3D reconstruction with Imaris software.On postoperative day(POD)3,both age groups exhibited reduced pain thresholds on the ipsilateral side,along with microglial activation in the dorsal horn.On POD 7,pain thresholds in young mice had returned to baseline with no significant microglial activation,while aged mice showed sustained reduction in pain thresholds,continuous microglial activation,and significant loss of inhibitory synapses without detectable changes in excitatory synapse density.These findings are consistent across both sexes,with no sex-related differences.Collectively,these results suggest that aging is associated with persistent postoperative pain,which correlates with microglial activation and inhibitory synapse loss.These insights advance our understanding of age-related pain vulnerability and may inform the development of more effective,targeted,and age-specific therapeutic strategies to prevent or alleviate persistent postoperative pain in elderly patients.
