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
Countries around the world have been making efforts to reduce pollutant emissions. However, the response of global black carbon(BC) aging to emission changes remains unclear. Using the Community Atmosphere Model versi...Countries around the world have been making efforts to reduce pollutant emissions. However, the response of global black carbon(BC) aging to emission changes remains unclear. Using the Community Atmosphere Model version 6 with a machine-learning-integrated four-mode version of the Modal Aerosol Module, we quantify global BC aging responses to emission reductions for 2011–2018 and for 2050 and 2100 under carbon neutrality. During 2011–18, global trends in BC aging degree(mass ratio of coatings to BC, R_(BC)) exhibited marked regional disparities, with a significant increase in China(5.4% yr^(-1)), which contrasts with minimal changes in the USA, Europe, and India. The divergence is attributed to opposing trends in secondary organic aerosol(SOA) and sulfate coatings, driven by regional changes in the emission ratios of corresponding coating precursors to BC(volatile organic compounds-VOCs/BC and SO_(2)/BC). Projections under carbon neutrality reveal that R_(BC) will increase globally by 47%(118%) in 2050(2100), with strong convergent increases expected across major source regions. The R_(BC) increase, primarily driven by enhanced SOA coatings due to sharper BC reductions relative to VOCs, will enhance the global BC mass absorption cross-section(MAC) by 11%(17%) in 2050(2100).Consequently, although the global BC burden will decline sharply by 60%(76%), the enhanced MAC partially offsets the magnitude of the decline in the BC direct radiative effect, resulting in the moderation of global BC DRE decreases to 88%(92%) of the BC burden reductions in 2050(2100). This study highlights the globally enhanced BC aging and light absorption capacity under carbon neutrality, thereby partly offsetting the impact of BC direct emission reductions on future changes in BC radiative effects globally.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
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
SKI family transcriptional corepressor 1(SKOR1also known as LbxCor1, Fussel15, or CORL1), is a member of the SKI family of proteins and is transcribed from a protein-coding gene located on chromosome 15 in humans, tha...SKI family transcriptional corepressor 1(SKOR1also known as LbxCor1, Fussel15, or CORL1), is a member of the SKI family of proteins and is transcribed from a protein-coding gene located on chromosome 15 in humans, that has a molecular weight of approximately 100 kDa. Skor1 is highly expressed in neurons in the central nervous system of both humans and rodents.展开更多
In modern ZnO varistors,traditional aging mechanisms based on increased power consumption are no longer relevant due to reduced power consumption during DC aging.Prolonged exposure to both AC and DC voltages results i...In modern ZnO varistors,traditional aging mechanisms based on increased power consumption are no longer relevant due to reduced power consumption during DC aging.Prolonged exposure to both AC and DC voltages results in increased leakage current,decreased breakdown voltage,and lower nonlinearity,ultimately compromising their protective performance.To investigate the evolution in electrical properties during DC aging,this work developed a finite element model based on Voronoi networks and conducted accelerated aging tests on commercial varistors.Throughout the aging process,current-voltage characteristics and Schottky barrier parameters were measured and analyzed.The results indicate that when subjected to constant voltage,current flows through regions with larger grain sizes,forming discharge channels.As aging progresses,the current focus increases on these channels,leading to a decline in the varistor’s overall performance.Furthermore,analysis of the Schottky barrier parameters shows that the changes in electrical performance during aging are non-monotonic.These findings offer theoretical support for understanding the aging mechanisms and condition assessment of modern stable ZnO varistors.展开更多
Aging is a physiological and complex process produced by accumulative age-dependent cellular damage,which significantly impacts brain regions like the hippocampus,an essential region involved in memory and learning.A ...Aging is a physiological and complex process produced by accumulative age-dependent cellular damage,which significantly impacts brain regions like the hippocampus,an essential region involved in memory and learning.A crucial factor contributing to this decline is the dysfunction of mitochondria,particularly those located at synapses.Synaptic mitochondria are specialized organelles that produce the energy required for synaptic transmission but are also important for calcium homeostasis at these sites.In contrast,non-synaptic mitochondria primarily involve cellular metabolism and long-term energy supply.Both pools of mitochondria differ in their form,proteome,functionality,and cellular role.The proper functioning of synaptic mitochondria depends on processes such as mitochondrial dynamics,transport,and quality control.However,synaptic mitochondria are particularly vulnerable to age-associated damage,characterized by oxidative stress,impaired energy production,and calcium dysregulation.These changes compromise synaptic transmission,reducing synaptic activity and cognitive decline during aging.In the context of neurodegenerative diseases such as Alzheimer’s,Parkinson’s,and Huntington’s,the decline of synaptic mitochondrial function is even more pronounced.These diseases are marked by pathological protein accumulation,disrupted mitochondrial dynamics,and heightened oxidative stress,accelerating synaptic dysfunction and neuronal loss.Due to their specialized role and location,synaptic mitochondria are among the first organelles to exhibit dysfunction,underscoring their critical role in disease progression.This review delves into the main differences at structural and functional levels between synaptic and non-synaptic mitochondria,emphasizing the vulnerability of synaptic mitochondria to the aging process and neurodegeneration.These approaches highlight the potential of targeting synaptic mitochondria to mitigate age-associated cognitive impairment and synaptic degeneration.This review emphasizes the distinct vulnerabilities of hippocampal synaptic mitochondria,highlighting their essential role in sustaining brain function throughout life and their promise as therapeutic targets for safeguarding the cognitive capacities of people of advanced age.展开更多
Background:Midlife lifestyle factors,including physical activity,are associated with late-life brain health,yet the role of aerobic exercise on structural brain health in early and mid-adulthood remains poorly underst...Background:Midlife lifestyle factors,including physical activity,are associated with late-life brain health,yet the role of aerobic exercise on structural brain health in early and mid-adulthood remains poorly understood.This study aimed to examine the effect of aerobic exercise on structural brain age and to explore potential mediators.Methods:In a single-blind,12-month randomized clinical trial,130 healthy participants aged 26-58 years were randomized into a moderate-to-vigorous intensity aerobic exercise group or a usual-care control group.The exercise group attended two supervised 60-min sessions per week in a laboratory setting plus engaged in home-based exercise to achieve 150 min of exercise per week.Brain-predicted age difference(brain-PAD)and cardiorespiratory fitness(CRF)were assessed at baseline and 12 months.Both intention-to-treat(ITT)and completers analyses(including participants who completed post-intervention assessments)were performed.Results:The 130 participants(67.7%female)had an age of 41.28±9.93 years(mean±SD).At baseline,higher CRF(peak oxygen uptake,VO_(2peak))was associated with smaller brain-PAD(β=-0.309,p=0.012).After the intervention,the exercise group showed a decrease in brainPAD(estimated mean difference(EMD)=-0.60;95%confidence interval(95%CI):-1.15 to-0.04;p=0.034)compared to the control group(EMD=0.35;95%CI:-0.21 to 0.92;p=0.217);time×group interaction(between-group difference(BGD)=-0.95;95%CI:-1.72 to-0.17;p=0.019).VO2peak improved in the exercise group(EMD=1.60;95%CI:0.29-2.90;p=0.017)compared to the control group(EMD=-0.78;95%CI:-2.17 to 0.60;p=0.265);time×group interaction(BGD=2.38;95%CI:0.52-4.25;p=0.015).Body composition,blood pressure,and brain-derived neurotrophic factor levels were unaffected.None of the proposed pathways statistically mediated the effect of exercise on brain-PAD.The results from completers were similar.Conclusion:Engaging in 12 months of moderate-to-vigorous exercise reduced brain-PAD in early-to-midlife adults.The pathways by which these effects occur remain unknown.展开更多
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.
基金supported by the National Natural Science Foundation of China (42505149,41925023,U2342223,42105069,and 91744208)the China Postdoctoral Science Foundation (2025M770303)+1 种基金the Fundamental Research Funds for the Central Universities (14380230)the Jiangsu Funding Program for Excellent Postdoctoral Talent,and Jiangsu Collaborative Innovation Center of Climate Change。
文摘Countries around the world have been making efforts to reduce pollutant emissions. However, the response of global black carbon(BC) aging to emission changes remains unclear. Using the Community Atmosphere Model version 6 with a machine-learning-integrated four-mode version of the Modal Aerosol Module, we quantify global BC aging responses to emission reductions for 2011–2018 and for 2050 and 2100 under carbon neutrality. During 2011–18, global trends in BC aging degree(mass ratio of coatings to BC, R_(BC)) exhibited marked regional disparities, with a significant increase in China(5.4% yr^(-1)), which contrasts with minimal changes in the USA, Europe, and India. The divergence is attributed to opposing trends in secondary organic aerosol(SOA) and sulfate coatings, driven by regional changes in the emission ratios of corresponding coating precursors to BC(volatile organic compounds-VOCs/BC and SO_(2)/BC). Projections under carbon neutrality reveal that R_(BC) will increase globally by 47%(118%) in 2050(2100), with strong convergent increases expected across major source regions. The R_(BC) increase, primarily driven by enhanced SOA coatings due to sharper BC reductions relative to VOCs, will enhance the global BC mass absorption cross-section(MAC) by 11%(17%) in 2050(2100).Consequently, although the global BC burden will decline sharply by 60%(76%), the enhanced MAC partially offsets the magnitude of the decline in the BC direct radiative effect, resulting in the moderation of global BC DRE decreases to 88%(92%) of the BC burden reductions in 2050(2100). This study highlights the globally enhanced BC aging and light absorption capacity under carbon neutrality, thereby partly offsetting the impact of BC direct emission reductions on future changes in BC radiative effects globally.
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.
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.
基金supported by Science Foundation Ireland (Grant 19/FFP/6666),Cure Parkinson’s (Grant CP:GO01)a PhD studentship from the Anatomical Society。
文摘SKI family transcriptional corepressor 1(SKOR1also known as LbxCor1, Fussel15, or CORL1), is a member of the SKI family of proteins and is transcribed from a protein-coding gene located on chromosome 15 in humans, that has a molecular weight of approximately 100 kDa. Skor1 is highly expressed in neurons in the central nervous system of both humans and rodents.
文摘In modern ZnO varistors,traditional aging mechanisms based on increased power consumption are no longer relevant due to reduced power consumption during DC aging.Prolonged exposure to both AC and DC voltages results in increased leakage current,decreased breakdown voltage,and lower nonlinearity,ultimately compromising their protective performance.To investigate the evolution in electrical properties during DC aging,this work developed a finite element model based on Voronoi networks and conducted accelerated aging tests on commercial varistors.Throughout the aging process,current-voltage characteristics and Schottky barrier parameters were measured and analyzed.The results indicate that when subjected to constant voltage,current flows through regions with larger grain sizes,forming discharge channels.As aging progresses,the current focus increases on these channels,leading to a decline in the varistor’s overall performance.Furthermore,analysis of the Schottky barrier parameters shows that the changes in electrical performance during aging are non-monotonic.These findings offer theoretical support for understanding the aging mechanisms and condition assessment of modern stable ZnO varistors.
基金supported by ANID FONDECYT No.1221178Centro Ciencia&Vida,FB210008,Financiamiento Basal para Centros Científicos y Tecnológicos de Excelencia de ANID to CTR.
文摘Aging is a physiological and complex process produced by accumulative age-dependent cellular damage,which significantly impacts brain regions like the hippocampus,an essential region involved in memory and learning.A crucial factor contributing to this decline is the dysfunction of mitochondria,particularly those located at synapses.Synaptic mitochondria are specialized organelles that produce the energy required for synaptic transmission but are also important for calcium homeostasis at these sites.In contrast,non-synaptic mitochondria primarily involve cellular metabolism and long-term energy supply.Both pools of mitochondria differ in their form,proteome,functionality,and cellular role.The proper functioning of synaptic mitochondria depends on processes such as mitochondrial dynamics,transport,and quality control.However,synaptic mitochondria are particularly vulnerable to age-associated damage,characterized by oxidative stress,impaired energy production,and calcium dysregulation.These changes compromise synaptic transmission,reducing synaptic activity and cognitive decline during aging.In the context of neurodegenerative diseases such as Alzheimer’s,Parkinson’s,and Huntington’s,the decline of synaptic mitochondrial function is even more pronounced.These diseases are marked by pathological protein accumulation,disrupted mitochondrial dynamics,and heightened oxidative stress,accelerating synaptic dysfunction and neuronal loss.Due to their specialized role and location,synaptic mitochondria are among the first organelles to exhibit dysfunction,underscoring their critical role in disease progression.This review delves into the main differences at structural and functional levels between synaptic and non-synaptic mitochondria,emphasizing the vulnerability of synaptic mitochondria to the aging process and neurodegeneration.These approaches highlight the potential of targeting synaptic mitochondria to mitigate age-associated cognitive impairment and synaptic degeneration.This review emphasizes the distinct vulnerabilities of hippocampal synaptic mitochondria,highlighting their essential role in sustaining brain function throughout life and their promise as therapeutic targets for safeguarding the cognitive capacities of people of advanced age.
基金funded by the National Institutes of Health and the National Heart,Lung,and Blood Institute(P01HL040962)。
文摘Background:Midlife lifestyle factors,including physical activity,are associated with late-life brain health,yet the role of aerobic exercise on structural brain health in early and mid-adulthood remains poorly understood.This study aimed to examine the effect of aerobic exercise on structural brain age and to explore potential mediators.Methods:In a single-blind,12-month randomized clinical trial,130 healthy participants aged 26-58 years were randomized into a moderate-to-vigorous intensity aerobic exercise group or a usual-care control group.The exercise group attended two supervised 60-min sessions per week in a laboratory setting plus engaged in home-based exercise to achieve 150 min of exercise per week.Brain-predicted age difference(brain-PAD)and cardiorespiratory fitness(CRF)were assessed at baseline and 12 months.Both intention-to-treat(ITT)and completers analyses(including participants who completed post-intervention assessments)were performed.Results:The 130 participants(67.7%female)had an age of 41.28±9.93 years(mean±SD).At baseline,higher CRF(peak oxygen uptake,VO_(2peak))was associated with smaller brain-PAD(β=-0.309,p=0.012).After the intervention,the exercise group showed a decrease in brainPAD(estimated mean difference(EMD)=-0.60;95%confidence interval(95%CI):-1.15 to-0.04;p=0.034)compared to the control group(EMD=0.35;95%CI:-0.21 to 0.92;p=0.217);time×group interaction(between-group difference(BGD)=-0.95;95%CI:-1.72 to-0.17;p=0.019).VO2peak improved in the exercise group(EMD=1.60;95%CI:0.29-2.90;p=0.017)compared to the control group(EMD=-0.78;95%CI:-2.17 to 0.60;p=0.265);time×group interaction(BGD=2.38;95%CI:0.52-4.25;p=0.015).Body composition,blood pressure,and brain-derived neurotrophic factor levels were unaffected.None of the proposed pathways statistically mediated the effect of exercise on brain-PAD.The results from completers were similar.Conclusion:Engaging in 12 months of moderate-to-vigorous exercise reduced brain-PAD in early-to-midlife adults.The pathways by which these effects occur remain unknown.
