Aging plays a critical role in determining the durability and long-term performance of asphalt pavements,as it is influenced by both external factors(e.g.,temperature,ultraviolet(UV)radiation,moisture,oxidative gases)...Aging plays a critical role in determining the durability and long-term performance of asphalt pavements,as it is influenced by both external factors(e.g.,temperature,ultraviolet(UV)radiation,moisture,oxidative gases)and internal factors such as binder composition.Although laboratory simulations of aging are well established for conventional bituminous binders,limited attention has been paid to replicating and evaluating aging processes in bio-based binders.This review provides a comprehensive analysis of current laboratory techniques for simulating and assessing binder aging,with a focus on two key areas:aging simulation protocols and evaluation methodologies.The analysis shows that although several efforts have been made to incorporate external aging factors into lab simulations,significant challenges persist,especially in the case of bio-based binders,which are characterized by a high variability in composition and limited understanding of their aging behavior.Current evaluation approaches also exhibit limitations.Improvements are needed in the molecular-level analysis of oxidation(e.g.,through more representative oxidation modelsin molecular dynamicssimulations),in the separation and quantification of binder constituents,and in the application of advanced techniques such as fluorescence microscopy to better characterize polymer dispersion.To enhance the reliability of laboratory simulations,future research should aim to improve the correlation between laboratory and field aging,define robust aging indexes,and refine characterization methods.These advancements are particularly critical for bio-based binders,whose performance is highly sensitive to aging and for which standard test protocols are still underdeveloped.A deeper understanding of aging mechanisms in both polymer-modified and biobased binders,along with improved analytical tools for assessing oxidative degradation and morphological changes,will be essential to support the development of sustainable,high-performance paving materials.展开更多
SKI family transcriptional corepressor 1(SKOR1also known as LbxCor1, Fussel15, or CORL1), is a member of the SKI family of proteins and is transcribed from a protein-coding gene located on chromosome 15 in humans, tha...SKI family transcriptional corepressor 1(SKOR1also known as LbxCor1, Fussel15, or CORL1), is a member of the SKI family of proteins and is transcribed from a protein-coding gene located on chromosome 15 in humans, that has a molecular weight of approximately 100 kDa. Skor1 is highly expressed in neurons in the central nervous system of both humans and rodents.展开更多
In modern ZnO varistors,traditional aging mechanisms based on increased power consumption are no longer relevant due to reduced power consumption during DC aging.Prolonged exposure to both AC and DC voltages results i...In modern ZnO varistors,traditional aging mechanisms based on increased power consumption are no longer relevant due to reduced power consumption during DC aging.Prolonged exposure to both AC and DC voltages results in increased leakage current,decreased breakdown voltage,and lower nonlinearity,ultimately compromising their protective performance.To investigate the evolution in electrical properties during DC aging,this work developed a finite element model based on Voronoi networks and conducted accelerated aging tests on commercial varistors.Throughout the aging process,current-voltage characteristics and Schottky barrier parameters were measured and analyzed.The results indicate that when subjected to constant voltage,current flows through regions with larger grain sizes,forming discharge channels.As aging progresses,the current focus increases on these channels,leading to a decline in the varistor’s overall performance.Furthermore,analysis of the Schottky barrier parameters shows that the changes in electrical performance during aging are non-monotonic.These findings offer theoretical support for understanding the aging mechanisms and condition assessment of modern stable ZnO varistors.展开更多
Aging is a physiological and complex process produced by accumulative age-dependent cellular damage,which significantly impacts brain regions like the hippocampus,an essential region involved in memory and learning.A ...Aging is a physiological and complex process produced by accumulative age-dependent cellular damage,which significantly impacts brain regions like the hippocampus,an essential region involved in memory and learning.A crucial factor contributing to this decline is the dysfunction of mitochondria,particularly those located at synapses.Synaptic mitochondria are specialized organelles that produce the energy required for synaptic transmission but are also important for calcium homeostasis at these sites.In contrast,non-synaptic mitochondria primarily involve cellular metabolism and long-term energy supply.Both pools of mitochondria differ in their form,proteome,functionality,and cellular role.The proper functioning of synaptic mitochondria depends on processes such as mitochondrial dynamics,transport,and quality control.However,synaptic mitochondria are particularly vulnerable to age-associated damage,characterized by oxidative stress,impaired energy production,and calcium dysregulation.These changes compromise synaptic transmission,reducing synaptic activity and cognitive decline during aging.In the context of neurodegenerative diseases such as Alzheimer’s,Parkinson’s,and Huntington’s,the decline of synaptic mitochondrial function is even more pronounced.These diseases are marked by pathological protein accumulation,disrupted mitochondrial dynamics,and heightened oxidative stress,accelerating synaptic dysfunction and neuronal loss.Due to their specialized role and location,synaptic mitochondria are among the first organelles to exhibit dysfunction,underscoring their critical role in disease progression.This review delves into the main differences at structural and functional levels between synaptic and non-synaptic mitochondria,emphasizing the vulnerability of synaptic mitochondria to the aging process and neurodegeneration.These approaches highlight the potential of targeting synaptic mitochondria to mitigate age-associated cognitive impairment and synaptic degeneration.This review emphasizes the distinct vulnerabilities of hippocampal synaptic mitochondria,highlighting their essential role in sustaining brain function throughout life and their promise as therapeutic targets for safeguarding the cognitive capacities of people of advanced age.展开更多
As the aging population continues to grow,age-related health issues are becoming increasingly prominent,attracting widespread attention and concern from society.While research on the mechanisms of aging is relatively ...As the aging population continues to grow,age-related health issues are becoming increasingly prominent,attracting widespread attention and concern from society.While research on the mechanisms of aging is relatively extensive,studies on the association between aging and related diseases remain limited.G.lucidum,a traditional medicinal fungus,has garnered significant attention due to its diverse bioactive properties.Recent studies have revealed that G.lucidum and its active components exhibit significant potential in anti-aging and regulating dysregulation of glucose and lipid metabolism.However,a comprehensive and detailed review of recent research findings has yet to be thoroughly explored.This paper summarizes and elucidates the latest advances in the pathological mechanisms of aging-related glucose and lipid metabolism disorders by retrieving data from databases such as X-mol and PubMed,provides a detailed account of the regulatory effects of G.lucidum’s primary active components on aging and lipid metabolism,and explores their potential mechanisms.Additionally,it discusses the application prospects of G.lucidum in the fields of anti-aging and metabolic regulation,aiming to provide a reference for research on aging-mediated lipid metabolism disorders and to lay a theoretical foundation for the further development and application of G.lucidum.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
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
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
The effects of artificial aging(T6)on the creep resistance with tensile stresses in the range of 50−80 MPa at 175℃were investigated for an extruded Mg−1.22Al−0.31Ca−0.44Mn(wt.%)alloy.The Guinier-Preston(G.P.)zones pr...The effects of artificial aging(T6)on the creep resistance with tensile stresses in the range of 50−80 MPa at 175℃were investigated for an extruded Mg−1.22Al−0.31Ca−0.44Mn(wt.%)alloy.The Guinier-Preston(G.P.)zones primarily precipitate in the sample aged at 200℃for 1 h(T6-200℃/1h),while the Al_(2)Ca phases mainly precipitate in the sample aged at 275℃for 8 h(T6-275℃/8h).The T6-200℃/1h sample exhibits excellent creep resistance,with a steady-state creep rate one order of magnitude lower than that of the T6-275℃/8h sample.The abnormally high stress exponent(~8.2)observed in the T6-200℃/1h sample is associated with the power-law breakdown mechanism.TEM analysis illuminates that the creep mechanism for the T6-200℃/1h sample is cross-slip between basal and prismatic dislocations,while the T6-275℃/8h sample exhibits a mixed mechanism of dislocation cross-slip and climb.Compared with the Al_(2)Ca phase,the dense G.P.zones effectively impede dislocation climb and glide during the creep process,demonstrating superior creep resistance of the T6-200℃/1h sample.展开更多
Despite recent advances in understanding the biology of aging,the field remains fragmented due to the lack of a central organizing hypothesis.Although there are ongoing debates on whether the aging process is programm...Despite recent advances in understanding the biology of aging,the field remains fragmented due to the lack of a central organizing hypothesis.Although there are ongoing debates on whether the aging process is programmed or stochastic,it is now evident that neither perspective alone can fully explain the complexity of aging.Here,we propose the pro-aging metabolic reprogramming(PAMRP)theory,which integrates and unifies the genetic-program and stochastic hypotheses.This theory posits that aging is driven by degenerative metabolic reprogramming(MRP)over time,requiring the emergence of pro-aging substrates and triggers(PASs and PATs)to predispose cells to cellular and genetic reprogramming(CRP and GRP).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
The aging process is an inexorable fact throughout our lives and is considered a major factor in develo ping neurological dysfunctions associated with cognitive,emotional,and motor impairments.Aging-associated neurode...The aging process is an inexorable fact throughout our lives and is considered a major factor in develo ping neurological dysfunctions associated with cognitive,emotional,and motor impairments.Aging-associated neurodegenerative diseases are characterized by the progressive loss of neuronal structure and function.展开更多
Anti-aging research has become a popular scientific field with the increasing prominence of population aging.Rare ginsenoside Compound K(CK)has attracted widespread attention as an emerging anti-aging active ingredien...Anti-aging research has become a popular scientific field with the increasing prominence of population aging.Rare ginsenoside Compound K(CK)has attracted widespread attention as an emerging anti-aging active ingredient.The anti-aging effect of ginsenosides is considered to be one of the important roles of ginsenosides,and Compound K,as the main deglycosylated metabolite of ginsenosides,has a comprehensive anti-aging effect as a highly active ingredient obtained by transformation under the action of microbiota.Recent studies have shown that ginsenosides have anti-photo-oxidation,anti-skin aging,free radical scavenging and immunostimulatory effects,which can effectively prevent skin photoaging.With the progress of modern natural medicine extraction technology and the deepening of the research on the anti-skin aging of ginsenosides'high active ingredients,it will promote the development and application of natural product protective skin photoaging preparations.The rare ginsenoside Compound K plays an important role in the improvement of skin health and anti-aging,which is mainly realized by increasing the activity of antioxidant enzymes,inducing the expression of related genes,reducing the content of oxidative damage substances,regulating the immune system,and influencing the expression of cell-cycle regulators and aging genes.A more comprehensive and in-depth study of the molecular mechanism of the anti-aging effect of rare ginsenoside Compound K will be one of the focuses of future research.展开更多
Currently,Mg-Gd-Y-Zn-Zr alloys face the issue of a long aging duration.To establish a short-time aging treatment route,the precipitation characteristics and their effects on mechanical properties during elevated-tempe...Currently,Mg-Gd-Y-Zn-Zr alloys face the issue of a long aging duration.To establish a short-time aging treatment route,the precipitation characteristics and their effects on mechanical properties during elevated-temperature heat treatment prior to low-temperature aging treatment,low-temperature single-stage aging treatment,and low-temperature two-stage aging treatment were studied.The following results were obtained:Wider intragranular lamellar phases,including 14-LPSO andγphases,are more easily obtained during long-term holding at heat treatment temperatures of 400℃and 450℃.Although these lamellar phases do not contribute to strengthening,they enhance ductility by hindering crack propagation.Micro-sizedβphases precipitate more readily at heat treatment temperatures of 300℃and 350℃.Intragranular needle-likeβphases are not effective strengthening phases,andβphase precipitating along grain boundaries form a networked distribution,which reduces ductility.The nano-sizedβ’phase,as the main strengthening phase,is more likely to precipitate during single-stage aging at temperatures of 200℃and 250℃.Theβ’phase formed at 200℃is denser,leading to higher strength,but requiring a longer aging time.For two-stage aging,which involves a primary-stage at 200℃for 8 to 12 h followed by a second-stage at 250℃for 10 h,the aging time is reduced to at least one-quarter of that required for single-stage aging at 200℃,ensuring strength while improving ductility.The formation of very dense nano-sizedβ’phases during the primary-stage aging facilitates the densification ofβ’phases during the subsequent second-stage aging.Additionally,the shortened aging time hinders the precipitation ofβphase along the grain boundaries,thus improving ductility.展开更多
A progressive decline in fertility is a well-documented aspect of female aging and is associated with a range of cellular and molecular alterations,including genomic instability and modifications in epigenetic regulat...A progressive decline in fertility is a well-documented aspect of female aging and is associated with a range of cellular and molecular alterations,including genomic instability and modifications in epigenetic regulation.Epigenetic clocks,which estimate biological age based on DNA methylation patterns,have been extensively utilized to evaluate general health status and the risk of various diseases.Despite their broad application,the utility of epigenetic clocks in assessing female reproductive health remains only partially characterized.This minireview consolidates recent advancements in the application of epigenetic clocks to evaluate the functional status of the female reproductive system.The objective is to investigate their potential for quantifying and predicting the biological age of reproductive tissues,thereby establishing a theoretical basis for clinical applications in reproductive medicine.To date,no comprehensive minireview has systematically examined multi-tissue epigenetic clock models in the context of female reproductive aging,positioning this minireview as a novel contribution to the field.展开更多
The marine economy has emerged as a vital driver of economic growth in both China and ASEAN countries.It encompasses a wide range of activities including fisheries,maritime transport,offshore oil and gas exploration,a...The marine economy has emerged as a vital driver of economic growth in both China and ASEAN countries.It encompasses a wide range of activities including fisheries,maritime transport,offshore oil and gas exploration,and marine tourism.At the same time,demographic structures are undergoing notable changes,with an increasing share of the older population.This trend of population aging has profound implications for various sectors,including the marine economy.Understanding the interplay between these dynamics is essential for sustainable development and policy-making.展开更多
It is increasingly recognized that young,chow-fed inbred mice poorly model the com-plexity of human carcinogenesis.In humans,age and adiposity are major risk factors for malignancies,but most genetically engineered mo...It is increasingly recognized that young,chow-fed inbred mice poorly model the com-plexity of human carcinogenesis.In humans,age and adiposity are major risk factors for malignancies,but most genetically engineered mouse models(GEMM)induce car-cinogenesis too rapidly to study these influences.Standard strains,such as C57BL/6,commonly used in GEMMs,further limit the exploration of aging and metabolic health effects.A similar challenge arises in modeling periodontitis,a disease influenced by aging,diabesity,and genetic architecture.We propose using diverse mouse popula-tions with hybrid vigor,such as the Collaborative Cross(CC)×Apc ^(Min) hybrid,to slow disease progression and better model human colorectal cancer(CRC)and comorbidi-ties.This perspective highlights the advantages of this model,where delayed car-cinogenesis reveals interactions with aging and adiposity.Unlike Apc ^(Min) mice,which develop cancer rapidly,CC×Apc ^(Min) hybrids recapitulate human-like progression.This facilitates the identification of modifier loci affecting inflammation,diet susceptibility,organ size,and polyposis distribution.The CC×Apc ^(Min) model offers a transformative platform for studying CRC as a disease of adulthood,reflecting its complex inter-play with aging and comorbidities.The insights gained from this approach will en-hance early detection,management,and treatment strategies for CRC and related conditions.展开更多
Objective:This study aimed to examine the influence of behavioral lifestyle factors on recent episodic memory retention capacity among young-old adults(aged 60-69 years)in China.The findings provide scientific evidenc...Objective:This study aimed to examine the influence of behavioral lifestyle factors on recent episodic memory retention capacity among young-old adults(aged 60-69 years)in China.The findings provide scientific evidence to inform proactive strategies to mitigate cognitive decline risk within China’s rapidly aging population.Methods:Utilizing data from the 2022 wave of the China Family Panel Studies(CFPS),a total of 2,772 adults aged 60-69 were included in the analytical sample.Recent episodic memory retention capacity(scored 0-5 points,based on self-reported assessment)served as the dependent variable.Six categories of behavioral lifestyle indicators(including exercise frequency,sleep quality,dietary patterns,etc.)were analyzed as independent variables.Associations were assessed using multivariate ordinal logistic regression models,controlling for relevant covariates.Results:Self-reported potential impairment in recent episodic memory was identified by 47.19%of respondents.Multivariate analysis revealed significant associations between behavioral lifestyle factors and memory retention capacity.Regular exercise(OR=1.297,95%CI:1.118-1.504),meat consumption(OR=1.765,95%CI:1.393-2.237),regular reading habits(OR=1.599,95%CI:1.283-1.992),and internet use(OR=1.413,95%CI:1.217-1.641)emerged as significant protective factors.Abnormal sleep duration was detrimentally associated with retention capacity(too short:OR=0.728,95%CI:0.591-0.897;too long:OR=0.810,95%CI:0.670-0.980).Significant associations were also observed for control variables:urban residence(OR=1.270,95%CI:1.100-1.467),high school education or above(OR=1.543,95%CI:1.293-1.841),and better self-rated health status(OR=1.156,95%CI:1.089-1.227)were positively correlated with better memory retention.Conclusions:Optimal sleep duration,regular physical exercise,meat intake,habitual reading,and internet engagement positively predict self-assessed recent episodic memory retention capacity in Chinese young-old adults.These findings underscore the potential for multi-faceted lifestyle interventions to enhance cog-nitive health in aging populations.Specifically,strategies should encompass community-based sleep hygiene management,tailored nutritional interventions(especially promoting adequate protein sources like meat),enhanced digital literacy and internet accessibility programs,and the promotion of age-appropriate physical activity initiatives.Furthermore,implementing culturally responsive strategies adapted to urban-rural contexts-such as deploying“mobile cognitive health units”in rural areas and fostering digital reading platforms in urban settings-is recommended to optimize intervention effectiveness.展开更多
The microstructure evolution and strengthening ability of natural aging(NA),delayed aging(DA),and DA after pre-aging(PDA)of Al-Mg-Si alloy were studied.Results show that small and unstable atomic clusters are generate...The microstructure evolution and strengthening ability of natural aging(NA),delayed aging(DA),and DA after pre-aging(PDA)of Al-Mg-Si alloy were studied.Results show that small and unstable atomic clusters are generated during NA,leading to the formation of low-density coarseβʺandβ′phases,thus reducing the strength of DA alloy.However,atomic clusters and GP zones with larger sizes and high Mg/Si molar ratio form during pre-aging treatment.They prevent the generation of clusters during NA and can serve as effective nucleation sites in subsequent artificial aging,which elevates the number density of fineβʺprecipitates and improves the alloy strength.After pre-aging at 175°C,the strengthening capacity of PDA alloy is restored,with hardness and yield strength reaching 95.1%and 101.9%of peak-aged alloy.展开更多
A Mg−3.2Bi−0.8Ca(BX31,wt.%)ternary alloy with a yield strength of~358.1 MPa was fabricated by hot extrusion,room-temperature(RT)rotary swaging and subsequent aging treatment.A fine grain structure(~2μm)and a few seco...A Mg−3.2Bi−0.8Ca(BX31,wt.%)ternary alloy with a yield strength of~358.1 MPa was fabricated by hot extrusion,room-temperature(RT)rotary swaging and subsequent aging treatment.A fine grain structure(~2μm)and a few secondary phases were observed in the as-extruded alloy,accompanied by a weak non-basal texture.After RT rotary swaging,the average grain size was reduced to~1μm via continuous dynamic recrystallization(CDRX).In addition,a large number of residual dislocations piled up within the grain interior,along with the dynamic precipitation of nano-phases.Peak aging occurred rapidly at 448 K for 35 min.After aging,the grain size hardly changed,the density of residual dislocations slightly decreased,and a large number of nano-precipitates were introduced at the dislocation pile-up sites.The grain boundary strengthening,dislocation strengthening and precipitation strengthening co-dominated the strength of the as-aged alloy.展开更多
文摘Aging plays a critical role in determining the durability and long-term performance of asphalt pavements,as it is influenced by both external factors(e.g.,temperature,ultraviolet(UV)radiation,moisture,oxidative gases)and internal factors such as binder composition.Although laboratory simulations of aging are well established for conventional bituminous binders,limited attention has been paid to replicating and evaluating aging processes in bio-based binders.This review provides a comprehensive analysis of current laboratory techniques for simulating and assessing binder aging,with a focus on two key areas:aging simulation protocols and evaluation methodologies.The analysis shows that although several efforts have been made to incorporate external aging factors into lab simulations,significant challenges persist,especially in the case of bio-based binders,which are characterized by a high variability in composition and limited understanding of their aging behavior.Current evaluation approaches also exhibit limitations.Improvements are needed in the molecular-level analysis of oxidation(e.g.,through more representative oxidation modelsin molecular dynamicssimulations),in the separation and quantification of binder constituents,and in the application of advanced techniques such as fluorescence microscopy to better characterize polymer dispersion.To enhance the reliability of laboratory simulations,future research should aim to improve the correlation between laboratory and field aging,define robust aging indexes,and refine characterization methods.These advancements are particularly critical for bio-based binders,whose performance is highly sensitive to aging and for which standard test protocols are still underdeveloped.A deeper understanding of aging mechanisms in both polymer-modified and biobased binders,along with improved analytical tools for assessing oxidative degradation and morphological changes,will be essential to support the development of sustainable,high-performance paving materials.
基金supported by Science Foundation Ireland (Grant 19/FFP/6666),Cure Parkinson’s (Grant CP:GO01)a PhD studentship from the Anatomical Society。
文摘SKI family transcriptional corepressor 1(SKOR1also known as LbxCor1, Fussel15, or CORL1), is a member of the SKI family of proteins and is transcribed from a protein-coding gene located on chromosome 15 in humans, that has a molecular weight of approximately 100 kDa. Skor1 is highly expressed in neurons in the central nervous system of both humans and rodents.
文摘In modern ZnO varistors,traditional aging mechanisms based on increased power consumption are no longer relevant due to reduced power consumption during DC aging.Prolonged exposure to both AC and DC voltages results in increased leakage current,decreased breakdown voltage,and lower nonlinearity,ultimately compromising their protective performance.To investigate the evolution in electrical properties during DC aging,this work developed a finite element model based on Voronoi networks and conducted accelerated aging tests on commercial varistors.Throughout the aging process,current-voltage characteristics and Schottky barrier parameters were measured and analyzed.The results indicate that when subjected to constant voltage,current flows through regions with larger grain sizes,forming discharge channels.As aging progresses,the current focus increases on these channels,leading to a decline in the varistor’s overall performance.Furthermore,analysis of the Schottky barrier parameters shows that the changes in electrical performance during aging are non-monotonic.These findings offer theoretical support for understanding the aging mechanisms and condition assessment of modern stable ZnO varistors.
基金supported by ANID FONDECYT No.1221178Centro Ciencia&Vida,FB210008,Financiamiento Basal para Centros Científicos y Tecnológicos de Excelencia de ANID to CTR.
文摘Aging is a physiological and complex process produced by accumulative age-dependent cellular damage,which significantly impacts brain regions like the hippocampus,an essential region involved in memory and learning.A crucial factor contributing to this decline is the dysfunction of mitochondria,particularly those located at synapses.Synaptic mitochondria are specialized organelles that produce the energy required for synaptic transmission but are also important for calcium homeostasis at these sites.In contrast,non-synaptic mitochondria primarily involve cellular metabolism and long-term energy supply.Both pools of mitochondria differ in their form,proteome,functionality,and cellular role.The proper functioning of synaptic mitochondria depends on processes such as mitochondrial dynamics,transport,and quality control.However,synaptic mitochondria are particularly vulnerable to age-associated damage,characterized by oxidative stress,impaired energy production,and calcium dysregulation.These changes compromise synaptic transmission,reducing synaptic activity and cognitive decline during aging.In the context of neurodegenerative diseases such as Alzheimer’s,Parkinson’s,and Huntington’s,the decline of synaptic mitochondrial function is even more pronounced.These diseases are marked by pathological protein accumulation,disrupted mitochondrial dynamics,and heightened oxidative stress,accelerating synaptic dysfunction and neuronal loss.Due to their specialized role and location,synaptic mitochondria are among the first organelles to exhibit dysfunction,underscoring their critical role in disease progression.This review delves into the main differences at structural and functional levels between synaptic and non-synaptic mitochondria,emphasizing the vulnerability of synaptic mitochondria to the aging process and neurodegeneration.These approaches highlight the potential of targeting synaptic mitochondria to mitigate age-associated cognitive impairment and synaptic degeneration.This review emphasizes the distinct vulnerabilities of hippocampal synaptic mitochondria,highlighting their essential role in sustaining brain function throughout life and their promise as therapeutic targets for safeguarding the cognitive capacities of people of advanced age.
基金supported by grants from Natural Science Foundation of Jilin Province(No.23JQ08,No.YDZJ202502 CXJD077,No.JLARS-2025-0802-09 and No.YDZJ202501ZY TS706).
文摘As the aging population continues to grow,age-related health issues are becoming increasingly prominent,attracting widespread attention and concern from society.While research on the mechanisms of aging is relatively extensive,studies on the association between aging and related diseases remain limited.G.lucidum,a traditional medicinal fungus,has garnered significant attention due to its diverse bioactive properties.Recent studies have revealed that G.lucidum and its active components exhibit significant potential in anti-aging and regulating dysregulation of glucose and lipid metabolism.However,a comprehensive and detailed review of recent research findings has yet to be thoroughly explored.This paper summarizes and elucidates the latest advances in the pathological mechanisms of aging-related glucose and lipid metabolism disorders by retrieving data from databases such as X-mol and PubMed,provides a detailed account of the regulatory effects of G.lucidum’s primary active components on aging and lipid metabolism,and explores their potential mechanisms.Additionally,it discusses the application prospects of G.lucidum in the fields of anti-aging and metabolic regulation,aiming to provide a reference for research on aging-mediated lipid metabolism disorders and to lay a theoretical foundation for the further development and application of G.lucidum.
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.
文摘Regenerative medicine is a promising therapeutic avenue for previously incurable diseases.As the risk of chronic and degenerative diseases significantly increases with age,the elderly population represents a major cohort for stem cell-based therapies.However,the regenerative potential of stem cells significantly decreases with advanced age and deteriorating health status of the donor.Therefore,the efficacy of autologous stem cell therapy is significantly compromised in older patients.To overcome these limitations,alternative strategies have been used to restore the age-and disease-depleted function of stem cells.These methods aim to restore the therapeutic efficacy of aged stem cells for autologous use.This article explores the effect of donor age and health status on the regenerative potential of stem cells.It further highlights the limitations of stem cell-based therapy for autologous treatment in the elderly.A comprehensive insight into the potential strategies to address the“age”and“disease”compromised regenerative potential of autologous stem cells is also presented.The information provided here serves as a valuable resource for physicians and patients for optimization of stem cellbased autologous therapy for aged patients.
基金supported by the National Natural Science Foundation of China (Nos. 52175322, 52271031)the Natural Science Foundation of Jilin Province, China (No. SKL202302015)。
文摘The effects of artificial aging(T6)on the creep resistance with tensile stresses in the range of 50−80 MPa at 175℃were investigated for an extruded Mg−1.22Al−0.31Ca−0.44Mn(wt.%)alloy.The Guinier-Preston(G.P.)zones primarily precipitate in the sample aged at 200℃for 1 h(T6-200℃/1h),while the Al_(2)Ca phases mainly precipitate in the sample aged at 275℃for 8 h(T6-275℃/8h).The T6-200℃/1h sample exhibits excellent creep resistance,with a steady-state creep rate one order of magnitude lower than that of the T6-275℃/8h sample.The abnormally high stress exponent(~8.2)observed in the T6-200℃/1h sample is associated with the power-law breakdown mechanism.TEM analysis illuminates that the creep mechanism for the T6-200℃/1h sample is cross-slip between basal and prismatic dislocations,while the T6-275℃/8h sample exhibits a mixed mechanism of dislocation cross-slip and climb.Compared with the Al_(2)Ca phase,the dense G.P.zones effectively impede dislocation climb and glide during the creep process,demonstrating superior creep resistance of the T6-200℃/1h sample.
文摘Despite recent advances in understanding the biology of aging,the field remains fragmented due to the lack of a central organizing hypothesis.Although there are ongoing debates on whether the aging process is programmed or stochastic,it is now evident that neither perspective alone can fully explain the complexity of aging.Here,we propose the pro-aging metabolic reprogramming(PAMRP)theory,which integrates and unifies the genetic-program and stochastic hypotheses.This theory posits that aging is driven by degenerative metabolic reprogramming(MRP)over time,requiring the emergence of pro-aging substrates and triggers(PASs and PATs)to predispose cells to cellular and genetic reprogramming(CRP and GRP).
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.
文摘The aging process is an inexorable fact throughout our lives and is considered a major factor in develo ping neurological dysfunctions associated with cognitive,emotional,and motor impairments.Aging-associated neurodegenerative diseases are characterized by the progressive loss of neuronal structure and function.
文摘Anti-aging research has become a popular scientific field with the increasing prominence of population aging.Rare ginsenoside Compound K(CK)has attracted widespread attention as an emerging anti-aging active ingredient.The anti-aging effect of ginsenosides is considered to be one of the important roles of ginsenosides,and Compound K,as the main deglycosylated metabolite of ginsenosides,has a comprehensive anti-aging effect as a highly active ingredient obtained by transformation under the action of microbiota.Recent studies have shown that ginsenosides have anti-photo-oxidation,anti-skin aging,free radical scavenging and immunostimulatory effects,which can effectively prevent skin photoaging.With the progress of modern natural medicine extraction technology and the deepening of the research on the anti-skin aging of ginsenosides'high active ingredients,it will promote the development and application of natural product protective skin photoaging preparations.The rare ginsenoside Compound K plays an important role in the improvement of skin health and anti-aging,which is mainly realized by increasing the activity of antioxidant enzymes,inducing the expression of related genes,reducing the content of oxidative damage substances,regulating the immune system,and influencing the expression of cell-cycle regulators and aging genes.A more comprehensive and in-depth study of the molecular mechanism of the anti-aging effect of rare ginsenoside Compound K will be one of the focuses of future research.
基金supported by the special fund for Science and Technology Innovation Team of Shanxi Province,Central Guiding Local Science and Technology Development Fund Projects(No.YDZJSX20231A029)National Natural Science Foundation of China(No.52205428)Fundamental Research Program of Shanxi Province(No.20210302124206).
文摘Currently,Mg-Gd-Y-Zn-Zr alloys face the issue of a long aging duration.To establish a short-time aging treatment route,the precipitation characteristics and their effects on mechanical properties during elevated-temperature heat treatment prior to low-temperature aging treatment,low-temperature single-stage aging treatment,and low-temperature two-stage aging treatment were studied.The following results were obtained:Wider intragranular lamellar phases,including 14-LPSO andγphases,are more easily obtained during long-term holding at heat treatment temperatures of 400℃and 450℃.Although these lamellar phases do not contribute to strengthening,they enhance ductility by hindering crack propagation.Micro-sizedβphases precipitate more readily at heat treatment temperatures of 300℃and 350℃.Intragranular needle-likeβphases are not effective strengthening phases,andβphase precipitating along grain boundaries form a networked distribution,which reduces ductility.The nano-sizedβ’phase,as the main strengthening phase,is more likely to precipitate during single-stage aging at temperatures of 200℃and 250℃.Theβ’phase formed at 200℃is denser,leading to higher strength,but requiring a longer aging time.For two-stage aging,which involves a primary-stage at 200℃for 8 to 12 h followed by a second-stage at 250℃for 10 h,the aging time is reduced to at least one-quarter of that required for single-stage aging at 200℃,ensuring strength while improving ductility.The formation of very dense nano-sizedβ’phases during the primary-stage aging facilitates the densification ofβ’phases during the subsequent second-stage aging.Additionally,the shortened aging time hinders the precipitation ofβphase along the grain boundaries,thus improving ductility.
文摘A progressive decline in fertility is a well-documented aspect of female aging and is associated with a range of cellular and molecular alterations,including genomic instability and modifications in epigenetic regulation.Epigenetic clocks,which estimate biological age based on DNA methylation patterns,have been extensively utilized to evaluate general health status and the risk of various diseases.Despite their broad application,the utility of epigenetic clocks in assessing female reproductive health remains only partially characterized.This minireview consolidates recent advancements in the application of epigenetic clocks to evaluate the functional status of the female reproductive system.The objective is to investigate their potential for quantifying and predicting the biological age of reproductive tissues,thereby establishing a theoretical basis for clinical applications in reproductive medicine.To date,no comprehensive minireview has systematically examined multi-tissue epigenetic clock models in the context of female reproductive aging,positioning this minireview as a novel contribution to the field.
文摘The marine economy has emerged as a vital driver of economic growth in both China and ASEAN countries.It encompasses a wide range of activities including fisheries,maritime transport,offshore oil and gas exploration,and marine tourism.At the same time,demographic structures are undergoing notable changes,with an increasing share of the older population.This trend of population aging has profound implications for various sectors,including the marine economy.Understanding the interplay between these dynamics is essential for sustainable development and policy-making.
基金Israel Cancer Research FoundationSamuel Waxman Cancer Research FoundationCore funding from Tel Aviv University。
文摘It is increasingly recognized that young,chow-fed inbred mice poorly model the com-plexity of human carcinogenesis.In humans,age and adiposity are major risk factors for malignancies,but most genetically engineered mouse models(GEMM)induce car-cinogenesis too rapidly to study these influences.Standard strains,such as C57BL/6,commonly used in GEMMs,further limit the exploration of aging and metabolic health effects.A similar challenge arises in modeling periodontitis,a disease influenced by aging,diabesity,and genetic architecture.We propose using diverse mouse popula-tions with hybrid vigor,such as the Collaborative Cross(CC)×Apc ^(Min) hybrid,to slow disease progression and better model human colorectal cancer(CRC)and comorbidi-ties.This perspective highlights the advantages of this model,where delayed car-cinogenesis reveals interactions with aging and adiposity.Unlike Apc ^(Min) mice,which develop cancer rapidly,CC×Apc ^(Min) hybrids recapitulate human-like progression.This facilitates the identification of modifier loci affecting inflammation,diet susceptibility,organ size,and polyposis distribution.The CC×Apc ^(Min) model offers a transformative platform for studying CRC as a disease of adulthood,reflecting its complex inter-play with aging and comorbidities.The insights gained from this approach will en-hance early detection,management,and treatment strategies for CRC and related conditions.
文摘Objective:This study aimed to examine the influence of behavioral lifestyle factors on recent episodic memory retention capacity among young-old adults(aged 60-69 years)in China.The findings provide scientific evidence to inform proactive strategies to mitigate cognitive decline risk within China’s rapidly aging population.Methods:Utilizing data from the 2022 wave of the China Family Panel Studies(CFPS),a total of 2,772 adults aged 60-69 were included in the analytical sample.Recent episodic memory retention capacity(scored 0-5 points,based on self-reported assessment)served as the dependent variable.Six categories of behavioral lifestyle indicators(including exercise frequency,sleep quality,dietary patterns,etc.)were analyzed as independent variables.Associations were assessed using multivariate ordinal logistic regression models,controlling for relevant covariates.Results:Self-reported potential impairment in recent episodic memory was identified by 47.19%of respondents.Multivariate analysis revealed significant associations between behavioral lifestyle factors and memory retention capacity.Regular exercise(OR=1.297,95%CI:1.118-1.504),meat consumption(OR=1.765,95%CI:1.393-2.237),regular reading habits(OR=1.599,95%CI:1.283-1.992),and internet use(OR=1.413,95%CI:1.217-1.641)emerged as significant protective factors.Abnormal sleep duration was detrimentally associated with retention capacity(too short:OR=0.728,95%CI:0.591-0.897;too long:OR=0.810,95%CI:0.670-0.980).Significant associations were also observed for control variables:urban residence(OR=1.270,95%CI:1.100-1.467),high school education or above(OR=1.543,95%CI:1.293-1.841),and better self-rated health status(OR=1.156,95%CI:1.089-1.227)were positively correlated with better memory retention.Conclusions:Optimal sleep duration,regular physical exercise,meat intake,habitual reading,and internet engagement positively predict self-assessed recent episodic memory retention capacity in Chinese young-old adults.These findings underscore the potential for multi-faceted lifestyle interventions to enhance cog-nitive health in aging populations.Specifically,strategies should encompass community-based sleep hygiene management,tailored nutritional interventions(especially promoting adequate protein sources like meat),enhanced digital literacy and internet accessibility programs,and the promotion of age-appropriate physical activity initiatives.Furthermore,implementing culturally responsive strategies adapted to urban-rural contexts-such as deploying“mobile cognitive health units”in rural areas and fostering digital reading platforms in urban settings-is recommended to optimize intervention effectiveness.
基金supported by the National Natural Science Foundation of China(No.52261007)the Science and Technology Project of Guangxi,China(No.GKAD22035039)the Opening Fund for Key Laboratory of New Processing Technology for Nonferrous Metal&Materials,Ministry of Education,Guilin University of Technology,China(Nos.22KF-11,22KF-14).
文摘The microstructure evolution and strengthening ability of natural aging(NA),delayed aging(DA),and DA after pre-aging(PDA)of Al-Mg-Si alloy were studied.Results show that small and unstable atomic clusters are generated during NA,leading to the formation of low-density coarseβʺandβ′phases,thus reducing the strength of DA alloy.However,atomic clusters and GP zones with larger sizes and high Mg/Si molar ratio form during pre-aging treatment.They prevent the generation of clusters during NA and can serve as effective nucleation sites in subsequent artificial aging,which elevates the number density of fineβʺprecipitates and improves the alloy strength.After pre-aging at 175°C,the strengthening capacity of PDA alloy is restored,with hardness and yield strength reaching 95.1%and 101.9%of peak-aged alloy.
基金supported by the financial supports from the National Key Research and Development Program of China(No.2021YFB3701100)the National Natural Science Foundation of China(Nos.51901204,52161023,52204407)+3 种基金Key Research and Development Plan of Shanxi Province,China(No.202102050201005)Science and Technology Project of Yunnan Precious Metal Laboratory,China(No.YPML-2023050208)Yunnan Science and Technology Planning Project,China(Nos.202201AU070010,202301AT070276,202302AB080008,202303AA080001)the Second Professional Practice Innovation Project of Yunnan University,China(No.ZC-22221620).
文摘A Mg−3.2Bi−0.8Ca(BX31,wt.%)ternary alloy with a yield strength of~358.1 MPa was fabricated by hot extrusion,room-temperature(RT)rotary swaging and subsequent aging treatment.A fine grain structure(~2μm)and a few secondary phases were observed in the as-extruded alloy,accompanied by a weak non-basal texture.After RT rotary swaging,the average grain size was reduced to~1μm via continuous dynamic recrystallization(CDRX).In addition,a large number of residual dislocations piled up within the grain interior,along with the dynamic precipitation of nano-phases.Peak aging occurred rapidly at 448 K for 35 min.After aging,the grain size hardly changed,the density of residual dislocations slightly decreased,and a large number of nano-precipitates were introduced at the dislocation pile-up sites.The grain boundary strengthening,dislocation strengthening and precipitation strengthening co-dominated the strength of the as-aged alloy.