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
The Cu0.9Cr0.1Zr alloy was deformed through continuous equal channel angular pressing(C-ECAP)through Route A,followed by liquid nitrogen cryogenic rolling(CR)and aging treated at 450℃.The microstructure,mechanical pr...The Cu0.9Cr0.1Zr alloy was deformed through continuous equal channel angular pressing(C-ECAP)through Route A,followed by liquid nitrogen cryogenic rolling(CR)and aging treated at 450℃.The microstructure,mechanical properties,and conductivity of the alloy were detected by electron back-scattered diffractometer,energy dispersive spectroscope,X-ray diffractometer,scanning electron microscope,and transmission electron microscope.The evolution mechanism of the texture during the deformation process and its influence on mechanical properties were analyzed.The results show that directional shear bands form in the CuCrZr alloy during the C-ECAP process,and the preferred orientation of the microstructure is consistent with the rolling direction.After deformation,the number of precipitated phases(mainly Cr)increases with the prolongation of aging time,accompanied by the appearance of micro-nanostructured fibrous structure in the alloy.After C-ECAP for three passes,75%CR deformation,and aging at 450℃ for 2 h,the tensile strength,microhardness,and conductivity reach 538 MPa,168 HV,and 80%IACS,respectively.CR,aging heat treatment,and formation of recrystallization texture are all conducive to the improvement of conductivity.展开更多
To investigate the effect of solution treatment and aging process parameters on the microstructure and mechanical properties of TB18 titanium alloy,process optimization research was conducted based on the mixed-level ...To investigate the effect of solution treatment and aging process parameters on the microstructure and mechanical properties of TB18 titanium alloy,process optimization research was conducted based on the mixed-level orthogonal experiment design of factor levels.Results show that through range analysis,the significance order of process parameters is determined as follows:solution cooling method>solution temperature>aging time>aging temperature>solution time.Considering the strength-ductility matching and engineering application requirements,the benchmark parameters are selected as solution time of 1 h,solution cooling method of air cooling(AC),aging temperature of 525℃,and aging time of 4 h.Furthermore,the effects of solution temperature in the range of 790–870℃ on the impact toughness and micro-fracture characteristics of the alloy were studied.The results reveal that the larger the area of shear lip and fibrous zone,and the smaller the area of radiation zone,the better the toughness of the alloy.With the increase in solution temperature,the length of secondary cracks on the fracture surface increases,the number of dimples increases,and the toughness is enhanced.Based on the collaborative optimization of strength and toughness,the optimal heat treatment process for TB18 alloy is determined as 870℃/1 h,AC+525℃/4 h,AC.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
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
Dear Editor,The long-term use of copper(Cu)fungicides to prevent downy mildew of vine led to the accumulation of Cu in vineyard topsoils(Komárek et al.,2010;Droz et al.,2021),which may alter the functioning and s...Dear Editor,The long-term use of copper(Cu)fungicides to prevent downy mildew of vine led to the accumulation of Cu in vineyard topsoils(Komárek et al.,2010;Droz et al.,2021),which may alter the functioning and sustainability of vineyard ecosystems(Cornu et al.,2022).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
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
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
In recent years,rising life expectancy has led to a significant increase in the prevalence of neurodegenerative disorders,including Alzheimer’s disease(AD),Parkinson’s disease,and age-related cognitive decline.Addit...In recent years,rising life expectancy has led to a significant increase in the prevalence of neurodegenerative disorders,including Alzheimer’s disease(AD),Parkinson’s disease,and age-related cognitive decline.Additionally,other neurological conditions such as glioblastoma,the most common and aggressive brain tumor in adults have been more frequently reported in aging populations.The brain itself is highly vulnerable to age-related changes,particularly disruptions in homeostatic regulation,which further contribute to its functional decline and heightened susceptibility to disease.This has led to a surge of interest in understanding the cellular and molecular mechanisms driving these changes.展开更多
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
Objective:To investigate the effect of a water-soluble nacre extract derived from Pinctada fucata on skeletal muscle aging.Methods:Naturally aged C57BL/6J mice received nacre extract mixed in chow for 12 weeks.Forelim...Objective:To investigate the effect of a water-soluble nacre extract derived from Pinctada fucata on skeletal muscle aging.Methods:Naturally aged C57BL/6J mice received nacre extract mixed in chow for 12 weeks.Forelimb grip strength,hanging performance,and locomotor activity were assessed.Skeletal muscle remodeling and signaling were evaluated by histology and immunostaining for fibrosis,contractile-marker features,senescence-and DNA damage-associated markers,inflammatory signaling,and mitochondrial proteins.Oxidative status was assessed by determining antioxidant capacity,lipid peroxidation,and oxidative DNA damage.Transcriptomic profiling was also performed,and selected targets were validated by quantitative RT-PCR and immunostaining.In addition,differentiated C2C12 myotubes were exposed to doxorubicin and treated with nacre extract;senescence-associated β-galactosidase,DNA damage signaling,and cell viability were measured.Results:Nacre extract increased forelimb grip strength and showed a positive trend in hanging performance without altering spontaneous locomotion.It also reduced collagen deposition,preserved contractile-marker immunoreactivity,attenuated senescence-and inflammation-associated signals,and increased mitochondrial protein immunoreactivity.Oxidative DNA damage was notably reduced by nacre extract.Transcriptomics indicated modulation of stress/redox programs and increased neurotrophic tyrosine kinase receptor type 2 expression,which were supported by tissue-level validation.In C2C12 myotubes,nacre extract suppressed doxorubicin-induced senescence-associated phenotypes without loss of cell viability.Conclusions:Water-soluble nacre extract mitigates skeletal muscle aging through coordinated modulation of oxidative stress,inflammation,mitochondrial features,and cellular senescence.展开更多
Background:Aging is a key risk factor for human health,causing damage to the brain and liver tissues.Accumulating evidence indicates that oxidative stress is a critical driver of the aging process.Shuangshen tablet(SS...Background:Aging is a key risk factor for human health,causing damage to the brain and liver tissues.Accumulating evidence indicates that oxidative stress is a critical driver of the aging process.Shuangshen tablet(SST),a functional food formulated with Ginseng Radix et Rhizoma and Apostichopus japonicus as main ingredients,possesses potential antioxidant and anti-aging properties.Thus,this study aimed to evaluate the anti-aging effects of SST using a D-galactose-induced aging model.Methods:The formula of SST was optimized via single-factor experiments and response surface methodology.Chemical components of SST were identified by UHPLC-Q-Exactive Orbitrap HRMS,and their in vitro antioxidant activity was determined.D-galactose-induced aging mice were intervened with SST,followed by detection of serum oxidative stress and pro-inflammatory factor levels,as well as the activities of superoxide dismutase(SOD),catalase(CAT),glutathione peroxidase(GSH-Px),and malondialdehyde(MDA)content in brain and liver tissues.Hematoxylin and eosin(HE)staining was used to observe brain and liver histopathological changes.Mechanistic studies were conducted to analyze the protein expression levels of Nrf2-HO-1 pathway-related proteins,phosphorylated PI3K(p-PI3K),and phosphorylated AKT(p-AKT).Acute and subacute toxicity tests were performed to evaluate the safety of SST.Results:A total of 46 active components were identified from SST,including ketones,terpenes,phenylpropanoids,and organic acids.SST intervention significantly regulated serum oxidative stress and pro-inflammatory factor levels in aging mice:it reduced MDA content in brain and liver tissues,increased SOD,CAT,and GSH-Px activities,and decreased serum tumor necrosis factor-alpha(TNF-α),interleukin-6(IL-6),and interleukin-1β(IL-1β)levels.HE staining showed that SST alleviated D-galactose-induced brain and liver damage.Mechanistically,SST mitigated oxidative damage by activating the Nrf2-HO-1 pathway and upregulating the protein expression of p-PI3K and p-AKT.Acute and subacute toxicity tests confirmed the safety of SST.Conclusion:SST can effectively delay the D-galactose-induced aging process by improving the oxidative stress signaling pathway,providing a theoretical basis for the development of antioxidant functional foods.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
Glassy polymers are widely used in biomedical applications in a solvent environment,yet their long-term performance is governed by the competing effects of physical aging and solvent-induced plasticization.Here,we dev...Glassy polymers are widely used in biomedical applications in a solvent environment,yet their long-term performance is governed by the competing effects of physical aging and solvent-induced plasticization.Here,we develop a constitutive model that explicitly couples the solvent concentration,structural relaxation,and mechanical response.This framework is built on a multiplicative decomposition of deformation and an Eyring-type flow rule,with structural evolution described by an effective temperature.A generalized shift factor is introduced to quantify how the solvent concentration and effective temperature jointly affect the relaxation time,thereby integrating physical aging and plasticization.The model is subsequently applied to methacrylate(MA)-based copolymer networks immersed in phosphate-buffered saline for up to nine months.Simulations accurately capture key experimental features,including the strong softening of highly swellable networks,the partial recovery due to aging,and the mitigating role of hydrophobic crosslinking in reducing solvent uptake.While the current single-mode description cannot reproduce the full relaxation spectrum,it establishes an efficient framework for predicting the long-term mechanical performance under coupled environmental and mechanical loading.This study provides a constitutive description of solvent-swollen glassy polymers,offering mechanistic insight into the interplay between plasticization and aging.Beyond biomedical MA networks,this framework establishes a foundation for predicting the long-term performance of polymer glasses under coupled aqueous environmental and mechanical loading.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
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
Alzheimer’s disease is initially thought to be caused by age-associated accumulation of plaques,in recent years,research has increasingly associated Alzheimer’s disease with lysosomal storage and metabolic disorders...Alzheimer’s disease is initially thought to be caused by age-associated accumulation of plaques,in recent years,research has increasingly associated Alzheimer’s disease with lysosomal storage and metabolic disorders,and the explanation of its pathogenesis has shifted from amyloid and tau accumulation to oxidative stress and impaired lipid and glucose metabolism aggravated by hypoxic conditions.However,the underlying mechanisms linking those cellular processes and conditions to disease progression have yet to be defined.Here,we applied a disease similarity approach to identify unknown molecular targets of Alzheimer’s disease by using transcriptomic data from congenital diseases known to increase Alzheimer’s disease risk,namely Down syndrome,Niemann-Pick type C disease,and mucopolysaccharidoses I.We uncovered common pathways,hub genes,and miRNAs across in vitro and in vivo models of these diseases as potential molecular targets for neuroprotection and amelioration of Alzheimer’s disease pathology,many of which have never been associated with Alzheimer’s disease.We then investigated common molecular alterations in brain samples from a Niemann-Pick type C disease mouse model by juxtaposing them with brain samples of both human and mouse models of Alzheimer’s disease.Detailed phenotypic,molecular,chronological,and biological aging analyses revealed that the Npc1tm(I1061T)Dso mouse model can serve as a potential short-lived in vivo model for brain aging and Alzheimer’s disease research.This research represents the first comprehensive approach to congenital disease association with neurodegeneration and a new perspective on Alzheimer’s disease research while highlighting shortcomings and lack of correlation in diverse in vitro models.Considering the lack of an Alzheimer’s disease mouse model that recapitulates the physiological hallmarks of brain aging,the short-lived Npc1^(tm(I1061T)Dso) mouse model can further accelerate the research in these fields and offer a unique model for understanding the molecular mechanisms of Alzheimer’s disease from a perspective of accelerated brain aging.展开更多
Ferroptosis is a newly recognized form of programmed cell death characterized by iron overload-dependent lipid peroxidation.These pathological phenomena are often observed in neurodegenerative diseases.Aging is an irr...Ferroptosis is a newly recognized form of programmed cell death characterized by iron overload-dependent lipid peroxidation.These pathological phenomena are often observed in neurodegenerative diseases.Aging is an irreversible process characterized by the deterioration of tissue and cell function.It has been shown to contribute to neurodegenerative diseases and increase susceptibility to ferroptosis.Therefore,ferroptosis may be involved in the progression of neurodegenerative diseases as a pathogenic factor,and aging is the common catalyst of both processes.The purpose of this review is to elucidate the latest progress on the mechanisms related to ferroptosis in neurodegenerative diseases,including iron overload,lipid peroxidation,antioxidant defense,cell membrane repair,and the regulation of autophagy and transcription factors.We also explored the relationship between ferroptosis and aging and reported that aging can induce ferroptosis by increasing iron overload,enhancing lipid peroxidation,and exacerbating autophagy disorders.Since ferroptosis is a pathogenic factor in neurodegenerative diseases,we screened gene bank databases and found that many genes associated with ferroptosis and neurodegenerative diseases overlap.Additionally,genes related to both the peroxidation pathway and ferroptosis are enriched.Ferroptosis occurs under conditions of age-related iron accumulation and lipid enrichment,as well as due to disorders in autophagy levels and transcription factors.Furthermore,in various neurodegenerative diseases,specific pathological changes or products can also contribute to the occurrence of ferroptosis.Finally,based on animal studies and clinical trials involving ferroptosis inhibitors,physical therapies,stem cell treatments,and exosome therapies in neurodegenerative diseases,it has been found that inhibiting ferroptosis can effectively reverse neurological dysfunction and cognitive impairment associated with these conditions.However,given various limitations,the conclusions of some animal studies and clinical trials have not been ideal,indicating that further large-scale research is necessary.Taken together,ferroptosis induces aging-related neurodegenerative diseases and neuronal cell death,triggering disease onset and progression.Ferroptosis inhibitors,physical therapies,stem cell treatments,and exosome therapies show great potential for inhibiting ferroptosis in neurodegenerative disease.展开更多
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.
基金Gansu Provincial Department of Education Industrial Support Program Project(2025CYZC-069)Central Government-Guided Local Science and Technology Development Fund Project(25ZYJE002)National Natural Science Foundation of China(51861022,51261016)。
文摘The Cu0.9Cr0.1Zr alloy was deformed through continuous equal channel angular pressing(C-ECAP)through Route A,followed by liquid nitrogen cryogenic rolling(CR)and aging treated at 450℃.The microstructure,mechanical properties,and conductivity of the alloy were detected by electron back-scattered diffractometer,energy dispersive spectroscope,X-ray diffractometer,scanning electron microscope,and transmission electron microscope.The evolution mechanism of the texture during the deformation process and its influence on mechanical properties were analyzed.The results show that directional shear bands form in the CuCrZr alloy during the C-ECAP process,and the preferred orientation of the microstructure is consistent with the rolling direction.After deformation,the number of precipitated phases(mainly Cr)increases with the prolongation of aging time,accompanied by the appearance of micro-nanostructured fibrous structure in the alloy.After C-ECAP for three passes,75%CR deformation,and aging at 450℃ for 2 h,the tensile strength,microhardness,and conductivity reach 538 MPa,168 HV,and 80%IACS,respectively.CR,aging heat treatment,and formation of recrystallization texture are all conducive to the improvement of conductivity.
基金Key Program of National Natural Science Foundation of China(52431001)。
文摘To investigate the effect of solution treatment and aging process parameters on the microstructure and mechanical properties of TB18 titanium alloy,process optimization research was conducted based on the mixed-level orthogonal experiment design of factor levels.Results show that through range analysis,the significance order of process parameters is determined as follows:solution cooling method>solution temperature>aging time>aging temperature>solution time.Considering the strength-ductility matching and engineering application requirements,the benchmark parameters are selected as solution time of 1 h,solution cooling method of air cooling(AC),aging temperature of 525℃,and aging time of 4 h.Furthermore,the effects of solution temperature in the range of 790–870℃ on the impact toughness and micro-fracture characteristics of the alloy were studied.The results reveal that the larger the area of shear lip and fibrous zone,and the smaller the area of radiation zone,the better the toughness of the alloy.With the increase in solution temperature,the length of secondary cracks on the fracture surface increases,the number of dimples increases,and the toughness is enhanced.Based on the collaborative optimization of strength and toughness,the optimal heat treatment process for TB18 alloy is determined as 870℃/1 h,AC+525℃/4 h,AC.
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financially supported by the Bordeaux Wine Interprofessional Council(French acronym CIVB)in the framework of the EXTRACUIVRE projectby the French National Research Institute for Agriculture,Food and Environment(INRAE)in the framework of the COPOFTEA projectpartially supported by the TSU Program Priority 2030,Russia。
文摘Dear Editor,The long-term use of copper(Cu)fungicides to prevent downy mildew of vine led to the accumulation of Cu in vineyard topsoils(Komárek et al.,2010;Droz et al.,2021),which may alter the functioning and sustainability of vineyard ecosystems(Cornu et al.,2022).
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.
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 the Swedish ResearchCouncil and the Swedish Brain Foundation,theCancer Research Funds of Radiumhemmet,theStrategic Research Area in Cancer(StratCan),the Strategic Research Area in Neuroscience(StratNeuro),the Swedish Cancer Society,theSwedish Childhood Cancer Foundation,theKarolinska Institutet Foundation,the InnoHKinitiative of the Innovation and TechnologyCommission of the Hong Kong SpecialAdministrative Region Government(to BJ).Openaccess funding is provided by the KarolinskaInstitute.
文摘In recent years,rising life expectancy has led to a significant increase in the prevalence of neurodegenerative disorders,including Alzheimer’s disease(AD),Parkinson’s disease,and age-related cognitive decline.Additionally,other neurological conditions such as glioblastoma,the most common and aggressive brain tumor in adults have been more frequently reported in aging populations.The brain itself is highly vulnerable to age-related changes,particularly disruptions in homeostatic regulation,which further contribute to its functional decline and heightened susceptibility to disease.This has led to a surge of interest in understanding the cellular and molecular mechanisms driving these changes.
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Objective:To investigate the effect of a water-soluble nacre extract derived from Pinctada fucata on skeletal muscle aging.Methods:Naturally aged C57BL/6J mice received nacre extract mixed in chow for 12 weeks.Forelimb grip strength,hanging performance,and locomotor activity were assessed.Skeletal muscle remodeling and signaling were evaluated by histology and immunostaining for fibrosis,contractile-marker features,senescence-and DNA damage-associated markers,inflammatory signaling,and mitochondrial proteins.Oxidative status was assessed by determining antioxidant capacity,lipid peroxidation,and oxidative DNA damage.Transcriptomic profiling was also performed,and selected targets were validated by quantitative RT-PCR and immunostaining.In addition,differentiated C2C12 myotubes were exposed to doxorubicin and treated with nacre extract;senescence-associated β-galactosidase,DNA damage signaling,and cell viability were measured.Results:Nacre extract increased forelimb grip strength and showed a positive trend in hanging performance without altering spontaneous locomotion.It also reduced collagen deposition,preserved contractile-marker immunoreactivity,attenuated senescence-and inflammation-associated signals,and increased mitochondrial protein immunoreactivity.Oxidative DNA damage was notably reduced by nacre extract.Transcriptomics indicated modulation of stress/redox programs and increased neurotrophic tyrosine kinase receptor type 2 expression,which were supported by tissue-level validation.In C2C12 myotubes,nacre extract suppressed doxorubicin-induced senescence-associated phenotypes without loss of cell viability.Conclusions:Water-soluble nacre extract mitigates skeletal muscle aging through coordinated modulation of oxidative stress,inflammation,mitochondrial features,and cellular senescence.
基金funded by Jilin Provincial Science and Technology Development Plan Project-Research and Development of Shuangshen Tablets(20210401123YY)Jilin Provincial Science and Technology Development Plan Project-Jilin Province High-quality and Authentic Medicinal Materials(Ginseng)Science and Technology Demonstration Base+(Ji'an Dadi Ginseng Industry Co.,Ltd.Ginseng Planting Base)(20220401114YY)Scientific Research Fund of Hebei Normal University of Science&Technology(2024YB019).
文摘Background:Aging is a key risk factor for human health,causing damage to the brain and liver tissues.Accumulating evidence indicates that oxidative stress is a critical driver of the aging process.Shuangshen tablet(SST),a functional food formulated with Ginseng Radix et Rhizoma and Apostichopus japonicus as main ingredients,possesses potential antioxidant and anti-aging properties.Thus,this study aimed to evaluate the anti-aging effects of SST using a D-galactose-induced aging model.Methods:The formula of SST was optimized via single-factor experiments and response surface methodology.Chemical components of SST were identified by UHPLC-Q-Exactive Orbitrap HRMS,and their in vitro antioxidant activity was determined.D-galactose-induced aging mice were intervened with SST,followed by detection of serum oxidative stress and pro-inflammatory factor levels,as well as the activities of superoxide dismutase(SOD),catalase(CAT),glutathione peroxidase(GSH-Px),and malondialdehyde(MDA)content in brain and liver tissues.Hematoxylin and eosin(HE)staining was used to observe brain and liver histopathological changes.Mechanistic studies were conducted to analyze the protein expression levels of Nrf2-HO-1 pathway-related proteins,phosphorylated PI3K(p-PI3K),and phosphorylated AKT(p-AKT).Acute and subacute toxicity tests were performed to evaluate the safety of SST.Results:A total of 46 active components were identified from SST,including ketones,terpenes,phenylpropanoids,and organic acids.SST intervention significantly regulated serum oxidative stress and pro-inflammatory factor levels in aging mice:it reduced MDA content in brain and liver tissues,increased SOD,CAT,and GSH-Px activities,and decreased serum tumor necrosis factor-alpha(TNF-α),interleukin-6(IL-6),and interleukin-1β(IL-1β)levels.HE staining showed that SST alleviated D-galactose-induced brain and liver damage.Mechanistically,SST mitigated oxidative damage by activating the Nrf2-HO-1 pathway and upregulating the protein expression of p-PI3K and p-AKT.Acute and subacute toxicity tests confirmed the safety of SST.Conclusion:SST can effectively delay the D-galactose-induced aging process by improving the oxidative stress signaling pathway,providing a theoretical basis for the development of antioxidant functional foods.
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.
基金the funding support from the Smart Medicine and Engineering Interdisciplinary Innovation Project of Ningbo University(No.ZHYG003)。
文摘Glassy polymers are widely used in biomedical applications in a solvent environment,yet their long-term performance is governed by the competing effects of physical aging and solvent-induced plasticization.Here,we develop a constitutive model that explicitly couples the solvent concentration,structural relaxation,and mechanical response.This framework is built on a multiplicative decomposition of deformation and an Eyring-type flow rule,with structural evolution described by an effective temperature.A generalized shift factor is introduced to quantify how the solvent concentration and effective temperature jointly affect the relaxation time,thereby integrating physical aging and plasticization.The model is subsequently applied to methacrylate(MA)-based copolymer networks immersed in phosphate-buffered saline for up to nine months.Simulations accurately capture key experimental features,including the strong softening of highly swellable networks,the partial recovery due to aging,and the mitigating role of hydrophobic crosslinking in reducing solvent uptake.While the current single-mode description cannot reproduce the full relaxation spectrum,it establishes an efficient framework for predicting the long-term mechanical performance under coupled environmental and mechanical loading.This study provides a constitutive description of solvent-swollen glassy polymers,offering mechanistic insight into the interplay between plasticization and aging.Beyond biomedical MA networks,this framework establishes a foundation for predicting the long-term performance of polymer glasses under coupled aqueous environmental and mechanical loading.
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.
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.
基金supported by the NIA/NIH(1K01AG060040).Studies performed by JN were funded by the NICHD/NIH(5R00HD096117)Microscopy Core Facility supported,in part,with funding from NIH-NCI Cancer Center Support Grant P30 CA016059.
文摘Alzheimer’s disease is initially thought to be caused by age-associated accumulation of plaques,in recent years,research has increasingly associated Alzheimer’s disease with lysosomal storage and metabolic disorders,and the explanation of its pathogenesis has shifted from amyloid and tau accumulation to oxidative stress and impaired lipid and glucose metabolism aggravated by hypoxic conditions.However,the underlying mechanisms linking those cellular processes and conditions to disease progression have yet to be defined.Here,we applied a disease similarity approach to identify unknown molecular targets of Alzheimer’s disease by using transcriptomic data from congenital diseases known to increase Alzheimer’s disease risk,namely Down syndrome,Niemann-Pick type C disease,and mucopolysaccharidoses I.We uncovered common pathways,hub genes,and miRNAs across in vitro and in vivo models of these diseases as potential molecular targets for neuroprotection and amelioration of Alzheimer’s disease pathology,many of which have never been associated with Alzheimer’s disease.We then investigated common molecular alterations in brain samples from a Niemann-Pick type C disease mouse model by juxtaposing them with brain samples of both human and mouse models of Alzheimer’s disease.Detailed phenotypic,molecular,chronological,and biological aging analyses revealed that the Npc1tm(I1061T)Dso mouse model can serve as a potential short-lived in vivo model for brain aging and Alzheimer’s disease research.This research represents the first comprehensive approach to congenital disease association with neurodegeneration and a new perspective on Alzheimer’s disease research while highlighting shortcomings and lack of correlation in diverse in vitro models.Considering the lack of an Alzheimer’s disease mouse model that recapitulates the physiological hallmarks of brain aging,the short-lived Npc1^(tm(I1061T)Dso) mouse model can further accelerate the research in these fields and offer a unique model for understanding the molecular mechanisms of Alzheimer’s disease from a perspective of accelerated brain aging.
基金supported by the National Natural Science Foundation of China,No.81101462(to LZ)the National Key Research and Development Program of China,No.2020YFC2005700(to LZ)+2 种基金the Natural Science Foundation of Liaoning Province,China,Nos.201602875,2019-KF-01-06(both LZ)Key Research and Development Program of Liaoning Province,China,No.2024JH2/102500021(to LZ)the Natural Science Foundation of Liaoning Province,China,No.2022-YGJC-56(to SS).
文摘Ferroptosis is a newly recognized form of programmed cell death characterized by iron overload-dependent lipid peroxidation.These pathological phenomena are often observed in neurodegenerative diseases.Aging is an irreversible process characterized by the deterioration of tissue and cell function.It has been shown to contribute to neurodegenerative diseases and increase susceptibility to ferroptosis.Therefore,ferroptosis may be involved in the progression of neurodegenerative diseases as a pathogenic factor,and aging is the common catalyst of both processes.The purpose of this review is to elucidate the latest progress on the mechanisms related to ferroptosis in neurodegenerative diseases,including iron overload,lipid peroxidation,antioxidant defense,cell membrane repair,and the regulation of autophagy and transcription factors.We also explored the relationship between ferroptosis and aging and reported that aging can induce ferroptosis by increasing iron overload,enhancing lipid peroxidation,and exacerbating autophagy disorders.Since ferroptosis is a pathogenic factor in neurodegenerative diseases,we screened gene bank databases and found that many genes associated with ferroptosis and neurodegenerative diseases overlap.Additionally,genes related to both the peroxidation pathway and ferroptosis are enriched.Ferroptosis occurs under conditions of age-related iron accumulation and lipid enrichment,as well as due to disorders in autophagy levels and transcription factors.Furthermore,in various neurodegenerative diseases,specific pathological changes or products can also contribute to the occurrence of ferroptosis.Finally,based on animal studies and clinical trials involving ferroptosis inhibitors,physical therapies,stem cell treatments,and exosome therapies in neurodegenerative diseases,it has been found that inhibiting ferroptosis can effectively reverse neurological dysfunction and cognitive impairment associated with these conditions.However,given various limitations,the conclusions of some animal studies and clinical trials have not been ideal,indicating that further large-scale research is necessary.Taken together,ferroptosis induces aging-related neurodegenerative diseases and neuronal cell death,triggering disease onset and progression.Ferroptosis inhibitors,physical therapies,stem cell treatments,and exosome therapies show great potential for inhibiting ferroptosis in neurodegenerative disease.
