INTRODUCTION With the expansion of the ageing population,cognitive decline has become an increas-ingly pressing challenge.1 As life expectancy increases,its socioeconomic burden is also increasing,highlighting the urg...INTRODUCTION With the expansion of the ageing population,cognitive decline has become an increas-ingly pressing challenge.1 As life expectancy increases,its socioeconomic burden is also increasing,highlighting the urgent need for effective interventions.Numerous studies suggest that specific dietary patterns and nutritional interventions may help mitigate cognitive decline associated with ageing.展开更多
AlSi7Mg is an age hardening aluminium alloy that is growing in popularity in additive manufacturing as its good processability makes it well suited to the powder bed fusion process,allowing for its use in the aerospac...AlSi7Mg is an age hardening aluminium alloy that is growing in popularity in additive manufacturing as its good processability makes it well suited to the powder bed fusion process,allowing for its use in the aerospace and automotive industries.The alloy relies on heat treatment to reach its peak strength,with precipitates in the Mg_(2) Si precipitation sequence providing the majority of this strengthening.Powder bed fusion,however,produces components with unique microstructures that differ to those of traditional manufacturing methods such as casting,meaning heat treatments must be carefully tailored for additively manufactured parts.This study therefore investigated the effects of solution treatment temperatures on the final properties and microstructures of T6 treated,additively manufactured AlSi7Mg.Due to the use of a heated build plate,samples aged from the as built and stress relieved conditions exhibited over ageing behaviour,necessitating a solution treatment step to induce useful strength properties.Solution treatments below 500℃were found to provide minimal strengthening upon ageing due to the pres-ence of theπ-Al_(18) Fe_(2)Mg_(7) Si_(10) phase,which reduced the amount of magnesium in solid solution and so reduced the age hardening response of the alloy by restricting the growth of strengthening precipitates.Solution treatments over 500℃,however,demonstrated excellent age hardening due to the replacement of theπ-Al_(18) Fe_(2)Mg_(7) Si_(10) phase with theβ-Al_(9)Fe_(2)Si_(2) phase,increasing the concentration of magnesium in solid solution and therefore improving its age hardening response.A T6 treatment then demonstrated an improvement in yield strength and ductility when compared to the as built state,but a decrease in tensile strength and impact toughness.The variability in the age hardening response of AlSi7Mg suggests that the careful selection of a solution treatment temperature is crucial to property optimisation.展开更多
This paper undertakes an analysis of labour market outcomes among aging population in Indian labour market by using household and personal level characteristics obtained from periodic labour force survey(PLFS)data for...This paper undertakes an analysis of labour market outcomes among aging population in Indian labour market by using household and personal level characteristics obtained from periodic labour force survey(PLFS)data for 2023-2024.It provides an analysis of the association of demographic and household characteristics with probability of choosing either paid-employment or self-employment by applying discrete choice model,after controlling for sample selection bias.By following strategic choice framework,endogenous sample selected probit model is used in finding out the role of different covariates in determining the chance of continuing work in self-employment and wage employment of any type after the age of statutory retirement.Social,economic,and other factors like gender are considered as key factors towards labour market participation of the aging population.This study examines the effects of age and education on decision to choose type of employment by the people beyond their statutory retirement age.The coefficient of female dummy is positive in regular-paid jobs and unpaid household work,but negative for own accounts work and employer irrespective of age cohorts suggesting that women are more likely to continue as regular paid jobs and unpaid household work,but less likely to be employer and own account worker as compared to men even after age 60 years and above.展开更多
The corrosion behaviors of Mg-10Gd-4.8Y-0.6Zr extruded-alloys with various ageing time were investigated by immersion test and electrochemical measurements.The results show that the corrosion rate of the experimental ...The corrosion behaviors of Mg-10Gd-4.8Y-0.6Zr extruded-alloys with various ageing time were investigated by immersion test and electrochemical measurements.The results show that the corrosion rate of the experimental alloy decreases with the increase of ageing time from 0 to 108 h.The corrosion resistance of the experimental alloy was found to increase with the increase of the size of the precipitate phases.The open circuit potential of the experimental alloy increases with the increase of the ageing time.The potentiodynamic polarization curves show that the cathodic over-potential increases with the increase of ageing time,leading to a decrease in the current density of anodic current plateau with the increase of ageing time.展开更多
Mierostruetural development of a commercial 7055 （Al-Zn-Mg-Cu）alloy is studied by transmission electron mieroseope（TEM） during the process of single-ageing for up to 48 h. It is observed that Guinier-Preston （GP...Mierostruetural development of a commercial 7055 （Al-Zn-Mg-Cu）alloy is studied by transmission electron mieroseope（TEM） during the process of single-ageing for up to 48 h. It is observed that Guinier-Preston （GP） zones are formed on { 111} planes when the sample is aged for a short time and grows up gradually with increase of ageing time. η＇ phase is formsed after ageing for 4 h at 120℃, having the orientation relationship with the matrix as[0 0 0 1]η＇//[1 1^- 1]Al and （1 0 1^- 1）η＇//（1 1 0）Al.η phase starts to occur after 24 h ageing and has an orientation relationship with matrix as [1^- 1 0 0]η//[1 1 0]Al and （0 0 0 1）η// （1 1 1）Al. Since the density of both η＇ phase and η phase particles is much lower than that of GP zone on aged alloy, GP zones are important to control the properties of the alloy.展开更多
A stochastic model of conducting crack propagation is presented to provide a conceptual framework dedicated to the study of the formation of fractal structure of dielectric ageing patterns as a result of a competition...A stochastic model of conducting crack propagation is presented to provide a conceptual framework dedicated to the study of the formation of fractal structure of dielectric ageing patterns as a result of a competition between random fluctuation growth and applied electric strength enhanced deterministic growth. The necessary and sufficient conditions resulting in fractal behaviour in dielectric ageing are found.展开更多
A kinetic model of dielectric ageing is presented. The central finding of this investigation is that there is a power-law relationship between the local electric field concentration and the rate of defect-tip initiate...A kinetic model of dielectric ageing is presented. The central finding of this investigation is that there is a power-law relationship between the local electric field concentration and the rate of defect-tip initiated conducting crack growth. By applying such a power-law conducting crack growth rate expression to the evaluation of the life of solid dielectrics, the empirical classical ageing law of insulation materials can be derived theoretically as a lobical result. All the results are universal and agree with the experimental data of oxide films.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,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
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
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
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
Mitochondrial dysfunction and oxidative stress are widely regarded as primary drivers of aging and are associated with several neurodegenerative diseases.The degeneration of motor neurons during aging is a critical pa...Mitochondrial dysfunction and oxidative stress are widely regarded as primary drivers of aging and are associated with several neurodegenerative diseases.The degeneration of motor neurons during aging is a critical pathological factor contributing to the progression of sarcopenia.However,the morphological and functional changes in mitochondria and their interplay in the degeneration of the neuromuscular junction during aging remain poorly understood.A defined systematic search of the Pub Med,Web of Science and Embase databases(last accessed on October 30,2024)was conducted with search terms including'mitochondria','aging'and'NMJ'.Clinical and preclinical studies of mitochondrial dysfunction and neuromuscular junction degeneration during aging.Twentyseven studies were included in this systematic review.This systematic review provides a summary of morphological,functional and biological changes in neuromuscular junction,mitochondrial morphology,biosynthesis,respiratory chain function,and mitophagy during aging.We focus on the interactions and mechanisms underlying the relationship between mitochondria and neuromuscular junctions during aging.Aging is characterized by significant reductions in mitochondrial fusion/fission cycles,biosynthesis,and mitochondrial quality control,which may lead to neuromuscular junction dysfunction,denervation and poor physical performance.Motor nerve terminals that exhibit redox sensitivity are among the first to exhibit abnormalities,ultimately leading to an early decline in muscle strength through impaired neuromuscular junction transmission function.Parg coactivator 1 alpha is a crucial molecule that regulates mitochondrial biogenesis and modulates various pathways,including the mitochondrial respiratory chain,energy deficiency,oxidative stress,and inflammation.Mitochondrial dysfunction is correlated with neuromuscular junction denervation and acetylcholine receptor fragmentation,resulting in muscle atrophy and a decrease in strength during aging.Physical therapy,pharmacotherapy,and gene therapy can alleviate the structural degeneration and functional deterioration of neuromuscular junction by restoring mitochondrial function.Therefore,mitochondria are considered potential targets for preserving neuromuscular junction morphology and function during aging to treat sarcopenia.展开更多
基金supported by the Shandong Second Medical University Overseas Visiting Scholar Programthe National Medical Research Council of Singapore (grant numbers NMRC/TA/0053/2016 and NMRC/CSA/INV/0009/2022)
文摘INTRODUCTION With the expansion of the ageing population,cognitive decline has become an increas-ingly pressing challenge.1 As life expectancy increases,its socioeconomic burden is also increasing,highlighting the urgent need for effective interventions.Numerous studies suggest that specific dietary patterns and nutritional interventions may help mitigate cognitive decline associated with ageing.
文摘AlSi7Mg is an age hardening aluminium alloy that is growing in popularity in additive manufacturing as its good processability makes it well suited to the powder bed fusion process,allowing for its use in the aerospace and automotive industries.The alloy relies on heat treatment to reach its peak strength,with precipitates in the Mg_(2) Si precipitation sequence providing the majority of this strengthening.Powder bed fusion,however,produces components with unique microstructures that differ to those of traditional manufacturing methods such as casting,meaning heat treatments must be carefully tailored for additively manufactured parts.This study therefore investigated the effects of solution treatment temperatures on the final properties and microstructures of T6 treated,additively manufactured AlSi7Mg.Due to the use of a heated build plate,samples aged from the as built and stress relieved conditions exhibited over ageing behaviour,necessitating a solution treatment step to induce useful strength properties.Solution treatments below 500℃were found to provide minimal strengthening upon ageing due to the pres-ence of theπ-Al_(18) Fe_(2)Mg_(7) Si_(10) phase,which reduced the amount of magnesium in solid solution and so reduced the age hardening response of the alloy by restricting the growth of strengthening precipitates.Solution treatments over 500℃,however,demonstrated excellent age hardening due to the replacement of theπ-Al_(18) Fe_(2)Mg_(7) Si_(10) phase with theβ-Al_(9)Fe_(2)Si_(2) phase,increasing the concentration of magnesium in solid solution and therefore improving its age hardening response.A T6 treatment then demonstrated an improvement in yield strength and ductility when compared to the as built state,but a decrease in tensile strength and impact toughness.The variability in the age hardening response of AlSi7Mg suggests that the careful selection of a solution treatment temperature is crucial to property optimisation.
文摘This paper undertakes an analysis of labour market outcomes among aging population in Indian labour market by using household and personal level characteristics obtained from periodic labour force survey(PLFS)data for 2023-2024.It provides an analysis of the association of demographic and household characteristics with probability of choosing either paid-employment or self-employment by applying discrete choice model,after controlling for sample selection bias.By following strategic choice framework,endogenous sample selected probit model is used in finding out the role of different covariates in determining the chance of continuing work in self-employment and wage employment of any type after the age of statutory retirement.Social,economic,and other factors like gender are considered as key factors towards labour market participation of the aging population.This study examines the effects of age and education on decision to choose type of employment by the people beyond their statutory retirement age.The coefficient of female dummy is positive in regular-paid jobs and unpaid household work,but negative for own accounts work and employer irrespective of age cohorts suggesting that women are more likely to continue as regular paid jobs and unpaid household work,but less likely to be employer and own account worker as compared to men even after age 60 years and above.
基金Project(51074186) supported by the National Natural Science Foundation of China
文摘The corrosion behaviors of Mg-10Gd-4.8Y-0.6Zr extruded-alloys with various ageing time were investigated by immersion test and electrochemical measurements.The results show that the corrosion rate of the experimental alloy decreases with the increase of ageing time from 0 to 108 h.The corrosion resistance of the experimental alloy was found to increase with the increase of the size of the precipitate phases.The open circuit potential of the experimental alloy increases with the increase of the ageing time.The potentiodynamic polarization curves show that the cathodic over-potential increases with the increase of ageing time,leading to a decrease in the current density of anodic current plateau with the increase of ageing time.
文摘Mierostruetural development of a commercial 7055 （Al-Zn-Mg-Cu）alloy is studied by transmission electron mieroseope（TEM） during the process of single-ageing for up to 48 h. It is observed that Guinier-Preston （GP） zones are formed on { 111} planes when the sample is aged for a short time and grows up gradually with increase of ageing time. η＇ phase is formsed after ageing for 4 h at 120℃, having the orientation relationship with the matrix as[0 0 0 1]η＇//[1 1^- 1]Al and （1 0 1^- 1）η＇//（1 1 0）Al.η phase starts to occur after 24 h ageing and has an orientation relationship with matrix as [1^- 1 0 0]η//[1 1 0]Al and （0 0 0 1）η// （1 1 1）Al. Since the density of both η＇ phase and η phase particles is much lower than that of GP zone on aged alloy, GP zones are important to control the properties of the alloy.
文摘A stochastic model of conducting crack propagation is presented to provide a conceptual framework dedicated to the study of the formation of fractal structure of dielectric ageing patterns as a result of a competition between random fluctuation growth and applied electric strength enhanced deterministic growth. The necessary and sufficient conditions resulting in fractal behaviour in dielectric ageing are found.
文摘A kinetic model of dielectric ageing is presented. The central finding of this investigation is that there is a power-law relationship between the local electric field concentration and the rate of defect-tip initiated conducting crack growth. By applying such a power-law conducting crack growth rate expression to the evaluation of the life of solid dielectrics, the empirical classical ageing law of insulation materials can be derived theoretically as a lobical result. All the results are universal and agree with the experimental data of oxide films.
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.
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 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 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.
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.
基金supported by grants from Collaborative Research Fund(Ref:C4032-21GF)General Research Grant(Ref:14114822)+1 种基金Group Research Scheme(Ref:3110146)Area of Excellence(Ref:Ao E/M-402/20)。
文摘Mitochondrial dysfunction and oxidative stress are widely regarded as primary drivers of aging and are associated with several neurodegenerative diseases.The degeneration of motor neurons during aging is a critical pathological factor contributing to the progression of sarcopenia.However,the morphological and functional changes in mitochondria and their interplay in the degeneration of the neuromuscular junction during aging remain poorly understood.A defined systematic search of the Pub Med,Web of Science and Embase databases(last accessed on October 30,2024)was conducted with search terms including'mitochondria','aging'and'NMJ'.Clinical and preclinical studies of mitochondrial dysfunction and neuromuscular junction degeneration during aging.Twentyseven studies were included in this systematic review.This systematic review provides a summary of morphological,functional and biological changes in neuromuscular junction,mitochondrial morphology,biosynthesis,respiratory chain function,and mitophagy during aging.We focus on the interactions and mechanisms underlying the relationship between mitochondria and neuromuscular junctions during aging.Aging is characterized by significant reductions in mitochondrial fusion/fission cycles,biosynthesis,and mitochondrial quality control,which may lead to neuromuscular junction dysfunction,denervation and poor physical performance.Motor nerve terminals that exhibit redox sensitivity are among the first to exhibit abnormalities,ultimately leading to an early decline in muscle strength through impaired neuromuscular junction transmission function.Parg coactivator 1 alpha is a crucial molecule that regulates mitochondrial biogenesis and modulates various pathways,including the mitochondrial respiratory chain,energy deficiency,oxidative stress,and inflammation.Mitochondrial dysfunction is correlated with neuromuscular junction denervation and acetylcholine receptor fragmentation,resulting in muscle atrophy and a decrease in strength during aging.Physical therapy,pharmacotherapy,and gene therapy can alleviate the structural degeneration and functional deterioration of neuromuscular junction by restoring mitochondrial function.Therefore,mitochondria are considered potential targets for preserving neuromuscular junction morphology and function during aging to treat sarcopenia.
