Aging is characterized by a decreased autophagic activity contributing to the intracellular deposition of damaged organelles and macromolecules.Autophagy is particularly challenging in neurons since autophagic vesicle...Aging is characterized by a decreased autophagic activity contributing to the intracellular deposition of damaged organelles and macromolecules.Autophagy is particularly challenging in neurons since autophagic vesicles are formed at the axonal tip and must be transported to the soma where final degradation occurs.Here,we examined if axonal transport of autophagic vesicles is altered during aging.We employed two-photon microscopy for in vivo imaging in the optic nerve of young and aged rats.In old animals(>18 months old),retrograde autophagic vesicle transport was significantly reduced with regard to motility and velocity.While activation of autophagy was decreased,expression of key proteins of the autophagy-lysosomal pathway including p62 and procathepsin D and the number of autophagolysosomes was increased.Maturation of autophagic vesicles was shifted to more distal regions of the axon and axonal lysosomal clearing was impaired.In a pull-down assay,the protein binding between dynein and dynactin was decreased by half,which could explain the retrograde axonal transport effects.Taken together,retrograde axonal autophagic vesicle transport in vivo is diminished during aging accompanied by decreased autophagy activation,alterations of the lysosomal pathway,and a reduced dynein-dynactin binding.展开更多
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
Subarachnoid hemorrhage is a subtype of stroke that causes severe neurological damage and is associated with poor long-term prognosis.Cognitive impairment is a major manifestation of long-term neurological dysfunction...Subarachnoid hemorrhage is a subtype of stroke that causes severe neurological damage and is associated with poor long-term prognosis.Cognitive impairment is a major manifestation of long-term neurological dysfunction in patients with subarachnoid hemorrhage.However,there is notable absence of biological markers to predict long-term prognosis in this patient population.Given the aging-like neurocognitive phenomena associated with subarachnoid hemorrhage,this study postulates that telomere length,a recognized biomarker for aging,could be used as a prognostic indicator for subarachnoid hemorrhage.A left internal carotid artery intravascular puncture mouse model was used to simulate subarachnoid hemorrhage.Comprehensive neurological test scores were obtained through neurobehavioral assessments conducted at one-month intervals.Concurrently,the relative telomere length was analyzed by quantitative polymerase chain reaction,which was performed using DNA extracted from ear notch and brain tissue after each assessment.Furthermore,proteomic analysis was employed to investigate differential protein expression in hippocampal tissue.Subarachnoid hemorrhage mice exhibited persistent neurocognitive impairment over a prolonged period of time.There was a significant positive correlation between telomere length and neurological test scores,confirming the usefulness of telomere length as a prognostic indicator in subarachnoid hemorrhage.Hippocampal tissue from subarachnoid hemorrhage mice showed reduced expression of acetyl-coenzyme A synthetase-2 and abnormalities in the expression of proteins related to ribosomes,energy metabolism,and cellular signal transduction.This study confirmed telomere shortening in the brain and metabolic disturbances in the hippocampi of subarachnoid hemorrhage mice.Thus,telomere length is a predictive marker for long-term impairment of cognitive function in mice following experimental subarachnoid hemorrhage.展开更多
Age-related macular degeneration(AMD)is the leading cause of irreversible vision loss in older adults,with early-stage features including subretinal lipid deposits and progressing to retinal geographic atrophy and cho...Age-related macular degeneration(AMD)is the leading cause of irreversible vision loss in older adults,with early-stage features including subretinal lipid deposits and progressing to retinal geographic atrophy and choroidal neovascularization in advanced stages.The dysregulation of ocular lipid metabolism,oxidative stress,and inflammation are critical risk factors for AMD pathogenesis.7-ketocholesterol(7-KC),a hallmark of ocular lipid metabolism disorders,is a significant component of subretinal lipid deposits in AMD patients,exhibiting toxicity to retinal cells and exacerbating lipotoxic aging.This review elaborates on the biosynthesis and metabolism of 7-KC in the retina,investigates its detoxification mechanisms by examining its binding proteins,and summarizes recent progress on kinase signaling pathways induced by 7-KC through inflammatory cytokines and intracellular effectors.The aim is to pinpoint potential pharmacological targets,nutritional compounds,and synthetic molecules to explore the potential of targeting 7-KC for AMD treatment.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
With the rapid increase in the aging population comes a rise in the incidence and prevalence of neurodegenerative diseases.Therefore,it is critical to understand the molecular changes that occur,which can either cause...With the rapid increase in the aging population comes a rise in the incidence and prevalence of neurodegenerative diseases.Therefore,it is critical to understand the molecular changes that occur,which can either cause disease or make brains resilient.Epigenetic changes are a common suspect and target,not only because they are among the hallmarks of aging,but also because they are flexible and could potentially be reversed.展开更多
Biological aging is a complex physiological process characterized by a decline in tissue function and the loss of cellular capabilities,which increase an individual's risk of various diseases[1].While genetic fact...Biological aging is a complex physiological process characterized by a decline in tissue function and the loss of cellular capabilities,which increase an individual's risk of various diseases[1].While genetic factors and lifestyle are key influences on biological aging,environmental factors also play a significant role.Given the rapid aging of the global population,elucidating the factors that influence biological aging is crucial for promoting healthy aging.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
It’s no secret that China has an aging population.Statistics from the Seventh National Population Census in 2020 showed that the country had 190.64 million people aged 65 or above,accounting for13.5 percent of its to...It’s no secret that China has an aging population.Statistics from the Seventh National Population Census in 2020 showed that the country had 190.64 million people aged 65 or above,accounting for13.5 percent of its total population.This proportion is now gradually approaching the internationally recognized threshold of 14 percent for a deeply aging society.China’s rapidly aging and mobility-limited population faces a severe shortage of millions of senior care workers.展开更多
Understanding how aging influences the thermal hazards of lithium-ion batteries(LIBs)is critical for enhancing their safety across a wide range of applications.This study systematically investigates the thermal runawa...Understanding how aging influences the thermal hazards of lithium-ion batteries(LIBs)is critical for enhancing their safety across a wide range of applications.This study systematically investigates the thermal runaway(TR)behavior of LIBs,with particular emphasis on combined-pathway aging,evaluated in terms of normalized usable capacity(U_(E)).Key thermal safety parameters,i.e.,TR triggering temperature,mass loss,and heat generation under diverse aging conditions,are quantified.To enable a fair comparison,thermal hazards are evaluated based on equivalent usable capacity,revealing that aged cells exhibit lower TR triggering temperatures and higher heat generation than fresh cells under thermal abuse with elevated thermal risks.Mechanistic analysis identifies lithium plating,solid electrolyte interphase(SEI)formation,and lithium depletion,particularly under high-temperature charging,as the dominant contributors to increased hazard.Using an aging-stressor matrix,a trade-off between high-C-rateinduced thermal instability and high-temperature-induced thermal stability is discovered and quantified,underscoring the strong dependence of thermal hazards on specific aging pathways.This work advances the fundamental understanding of aging-induced safety risks in LIBs and offers practical guidance for the development of safer battery systems,optimized charging protocols,and improved battery management strategies across applications in electric vehicles,consumer electronics,and grid-scale energy storage.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
基金China Scholarship Council(CSCto XL)and a generous heritage donation from Bettina Fischer,Germany(to JCK).
文摘Aging is characterized by a decreased autophagic activity contributing to the intracellular deposition of damaged organelles and macromolecules.Autophagy is particularly challenging in neurons since autophagic vesicles are formed at the axonal tip and must be transported to the soma where final degradation occurs.Here,we examined if axonal transport of autophagic vesicles is altered during aging.We employed two-photon microscopy for in vivo imaging in the optic nerve of young and aged rats.In old animals(>18 months old),retrograde autophagic vesicle transport was significantly reduced with regard to motility and velocity.While activation of autophagy was decreased,expression of key proteins of the autophagy-lysosomal pathway including p62 and procathepsin D and the number of autophagolysosomes was increased.Maturation of autophagic vesicles was shifted to more distal regions of the axon and axonal lysosomal clearing was impaired.In a pull-down assay,the protein binding between dynein and dynactin was decreased by half,which could explain the retrograde axonal transport effects.Taken together,retrograde axonal autophagic vesicle transport in vivo is diminished during aging accompanied by decreased autophagy activation,alterations of the lysosomal pathway,and a reduced dynein-dynactin binding.
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National Natural Science Foundation of China,No.81901336(to JM).
文摘Subarachnoid hemorrhage is a subtype of stroke that causes severe neurological damage and is associated with poor long-term prognosis.Cognitive impairment is a major manifestation of long-term neurological dysfunction in patients with subarachnoid hemorrhage.However,there is notable absence of biological markers to predict long-term prognosis in this patient population.Given the aging-like neurocognitive phenomena associated with subarachnoid hemorrhage,this study postulates that telomere length,a recognized biomarker for aging,could be used as a prognostic indicator for subarachnoid hemorrhage.A left internal carotid artery intravascular puncture mouse model was used to simulate subarachnoid hemorrhage.Comprehensive neurological test scores were obtained through neurobehavioral assessments conducted at one-month intervals.Concurrently,the relative telomere length was analyzed by quantitative polymerase chain reaction,which was performed using DNA extracted from ear notch and brain tissue after each assessment.Furthermore,proteomic analysis was employed to investigate differential protein expression in hippocampal tissue.Subarachnoid hemorrhage mice exhibited persistent neurocognitive impairment over a prolonged period of time.There was a significant positive correlation between telomere length and neurological test scores,confirming the usefulness of telomere length as a prognostic indicator in subarachnoid hemorrhage.Hippocampal tissue from subarachnoid hemorrhage mice showed reduced expression of acetyl-coenzyme A synthetase-2 and abnormalities in the expression of proteins related to ribosomes,energy metabolism,and cellular signal transduction.This study confirmed telomere shortening in the brain and metabolic disturbances in the hippocampi of subarachnoid hemorrhage mice.Thus,telomere length is a predictive marker for long-term impairment of cognitive function in mice following experimental subarachnoid hemorrhage.
文摘Age-related macular degeneration(AMD)is the leading cause of irreversible vision loss in older adults,with early-stage features including subretinal lipid deposits and progressing to retinal geographic atrophy and choroidal neovascularization in advanced stages.The dysregulation of ocular lipid metabolism,oxidative stress,and inflammation are critical risk factors for AMD pathogenesis.7-ketocholesterol(7-KC),a hallmark of ocular lipid metabolism disorders,is a significant component of subretinal lipid deposits in AMD patients,exhibiting toxicity to retinal cells and exacerbating lipotoxic aging.This review elaborates on the biosynthesis and metabolism of 7-KC in the retina,investigates its detoxification mechanisms by examining its binding proteins,and summarizes recent progress on kinase signaling pathways induced by 7-KC through inflammatory cytokines and intracellular effectors.The aim is to pinpoint potential pharmacological targets,nutritional compounds,and synthetic molecules to explore the potential of targeting 7-KC for AMD treatment.
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David and Inez Myers Foundation,the Israeli Ministry of Science and Technology(MOST)The Israel Science Foundation(No.422/23)(to DT).
文摘With the rapid increase in the aging population comes a rise in the incidence and prevalence of neurodegenerative diseases.Therefore,it is critical to understand the molecular changes that occur,which can either cause disease or make brains resilient.Epigenetic changes are a common suspect and target,not only because they are among the hallmarks of aging,but also because they are flexible and could potentially be reversed.
基金support from the Shenzhen Science and Technology program(grant number 202208183000115)。
文摘Biological aging is a complex physiological process characterized by a decline in tissue function and the loss of cellular capabilities,which increase an individual's risk of various diseases[1].While genetic factors and lifestyle are key influences on biological aging,environmental factors also play a significant role.Given the rapid aging of the global population,elucidating the factors that influence biological aging is crucial for promoting healthy aging.
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.
文摘It’s no secret that China has an aging population.Statistics from the Seventh National Population Census in 2020 showed that the country had 190.64 million people aged 65 or above,accounting for13.5 percent of its total population.This proportion is now gradually approaching the internationally recognized threshold of 14 percent for a deeply aging society.China’s rapidly aging and mobility-limited population faces a severe shortage of millions of senior care workers.
文摘Understanding how aging influences the thermal hazards of lithium-ion batteries(LIBs)is critical for enhancing their safety across a wide range of applications.This study systematically investigates the thermal runaway(TR)behavior of LIBs,with particular emphasis on combined-pathway aging,evaluated in terms of normalized usable capacity(U_(E)).Key thermal safety parameters,i.e.,TR triggering temperature,mass loss,and heat generation under diverse aging conditions,are quantified.To enable a fair comparison,thermal hazards are evaluated based on equivalent usable capacity,revealing that aged cells exhibit lower TR triggering temperatures and higher heat generation than fresh cells under thermal abuse with elevated thermal risks.Mechanistic analysis identifies lithium plating,solid electrolyte interphase(SEI)formation,and lithium depletion,particularly under high-temperature charging,as the dominant contributors to increased hazard.Using an aging-stressor matrix,a trade-off between high-C-rateinduced thermal instability and high-temperature-induced thermal stability is discovered and quantified,underscoring the strong dependence of thermal hazards on specific aging pathways.This work advances the fundamental understanding of aging-induced safety risks in LIBs and offers practical guidance for the development of safer battery systems,optimized charging protocols,and improved battery management strategies across applications in electric vehicles,consumer electronics,and grid-scale energy storage.
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.
