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
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
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
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
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
BACKGROUND Successful aging(SA)refers to the ability to maintain high levels of physical,cognitive,psychological,and social engagement in old age,with high cognitive function being the key to achieving SA.AIM To explo...BACKGROUND Successful aging(SA)refers to the ability to maintain high levels of physical,cognitive,psychological,and social engagement in old age,with high cognitive function being the key to achieving SA.AIM To explore the potential characteristics of the brain network and functional connectivity(FC)of SA.METHODS Twenty-six SA individuals and 47 usual aging individuals were recruited from community-dwelling elderly,which were taken the magnetic resonance imaging scan and the global cognitive function assessment by Mini Mental State Examination(MMSE).The resting state-functional magnetic resonance imaging data were preprocessed by DPABISurf,and the brain functional network was conducted by DPABINet.The support vector machine model was constructed with altered functional connectivities to evaluate the identification value of SA.RESULTS The results found that the 6 inter-network FCs of 5 brain networks were significantly altered and related to MMSE performance.The FC of the right orbital part of the middle frontal gyrus and right angular gyrus was mostly increased and positively related to MMSE score,and the FC of the right supramarginal gyrus and right temporal pole:Middle temporal gyrus was the only one decreased and negatively related to MMSE score.All 17 significantly altered FCs of SA were taken into the support vector machine model,and the area under the curve was 0.895.CONCLUSION The identification of key brain networks and FC of SA could help us better understand the brain mechanism and further explore neuroimaging biomarkers of SA.展开更多
Regulated cell death(such as apoptosis,necroptosis,pyroptosis,autophagy,cuproptosis,ferroptosis,disulfidptosis)involves complex signaling pathways and molecular effectors,and has been proven to be an important regulat...Regulated cell death(such as apoptosis,necroptosis,pyroptosis,autophagy,cuproptosis,ferroptosis,disulfidptosis)involves complex signaling pathways and molecular effectors,and has been proven to be an important regulatory mechanism for regulating neuronal aging and death.However,excessive activation of regulated cell death may lead to the progression of aging-related diseases.This review summarizes recent advances in the understanding of seven forms of regulated cell death in age-related diseases.Notably,the newly identified ferroptosis and cuproptosis have been implicated in the risk of cognitive impairment and neurodegenerative diseases.These forms of cell death exacerbate disease progression by promoting inflammation,oxidative stress,and pathological protein aggregation.The review also provides an overview of key signaling pathways and crosstalk mechanisms among these regulated cell death forms,with a focus on ferroptosis,cuproptosis,and disulfidptosis.For instance,FDX1 directly induces cuproptosis by regulating copper ion valency and dihydrolipoamide S-acetyltransferase aggregation,while copper mediates glutathione peroxidase 4 degradation,enhancing ferroptosis sensitivity.Additionally,inhibiting the Xc-transport system to prevent ferroptosis can increase disulfide formation and shift the NADP^(+)/NADPH ratio,transitioning ferroptosis to disulfidptosis.These insights help to uncover the potential connections among these novel regulated cell death forms and differentiate them from traditional regulated cell death mechanisms.In conclusion,identifying key targets and their crosstalk points among various regulated cell death pathways may aid in developing specific biomarkers to reverse the aging clock and treat age-related neurodegenerative conditions.展开更多
The oral cavity is a complex physiological community encompassing a wide range of microorganisms.Dysbiosis of oral microbiota can lead to various oral infectious diseases,such as periodontitis and tooth decay,and even...The oral cavity is a complex physiological community encompassing a wide range of microorganisms.Dysbiosis of oral microbiota can lead to various oral infectious diseases,such as periodontitis and tooth decay,and even affect systemic health,including brain aging and neurodegenerative diseases.Recent studies have highlighted how oral microbes might be involved in brain aging and neurodegeneration,indicating potential avenues for intervention strategies.In this review,we summarize clinical evidence demonstrating a link between oral microbes/oral infectious diseases and brain aging/neurodegenerative diseases,and dissect potential mechanisms by which oral microbes contribute to brain aging and neurodegeneration.We also highlight advances in therapeutic development grounded in the realm of oral microbes,with the goal of advancing brain health and promoting healthy aging.展开更多
Recent reports suggest that aging is not solely a physiological process in living beings;instead, it should be considered a pathological process or disease(Amorim et al., 2022). Consequently, this process involves a w...Recent reports suggest that aging is not solely a physiological process in living beings;instead, it should be considered a pathological process or disease(Amorim et al., 2022). Consequently, this process involves a wide range of factors, spanning from genetic to environmental factors, and even includes the gut microbiome(GM)(Mayer et al., 2022). All these processes coincide at some point in the inflammatory process, oxidative stress, and apoptosis, at different degrees in various organs and systems that constitute a living organism(Mayer et al., 2022;AguilarHernández et al., 2023).展开更多
Although magnesium-aluminum alloys,such as AZ80 and AZ91 have promising application potential in automotive,high-speed train and aerospace fields,their age-hardening response is generally not very appreciable.In this ...Although magnesium-aluminum alloys,such as AZ80 and AZ91 have promising application potential in automotive,high-speed train and aerospace fields,their age-hardening response is generally not very appreciable.In this work,the aging-hardening response of AZ80 alloy was effectively enhanced by applying cold-rolling deformation before conducting conventional aging treatment at 200°C.Compared to the directly aged sample,the yield strength of the pre-rolling and aged sample was increased by 35 MPa.Electron microscope examination confirmed that profuse{10¯11}and{10¯11}-{10¯12}twins,consisting of high density of dislocations and stacking faults,were generated by cold rolling.Blocky or ellipsoidal Mg_(17)Al_(12)precipitates formed at the twin boundaries(TBs)during subsequent aging treatment.Crystallographic analysis indicated that the precipitates at{10¯11}TBs always held an identical Potter OR with both the matrix and twin,while the precipitates at{10¯11}-{10¯12}TBs exhibited three different ORs:Burgers OR,Potter OR and P-S OR with either the matrix or the twin.Moreover,recrystallized grains were found inside{10¯11}-{10¯12}double twins after peak-aging at 200°C,implying that precipitation and recrystallization might occur concurrently along TBs at a relatively low temperature.It was speculated that the highly stored energy inside twins and the high elastic energy between the precipitates and twins were driving factors for the occurrence of recrystallization.展开更多
Although the plastic loading can enhance creep deformation and yield strength,the anisotropic Stress Relaxation Aging(SRA)behavior and mechanism under plastic loading remain unclear,which presents a significant challe...Although the plastic loading can enhance creep deformation and yield strength,the anisotropic Stress Relaxation Aging(SRA)behavior and mechanism under plastic loading remain unclear,which presents a significant challenge in accurately shaping aluminum alloy panels.In this study,the SRA behavior of 2195-T4 Al-Cu-Li alloys were thoroughly studied under initial loading stresses within the elastic(210/250 MPa)and plastic(380/420 MPa)ranges at 180℃by stress relaxation and tensile tests as well as microstructure characterization.The findings reveal that compared with those under elastic loadings,in-plane anisotropy(IPA)values of the stress relaxation amount,yield strength and fracture elongation under plastic loadings are reduced by 60%–80%,70%–90% and 72%–89%,respectively.Similarly,IPA values of precipitate size in grains and PrecipitationFree Zones(PFZ)width at grain boundaries under plastic loading decrease by 31.4%and 94.4%respectively.These results indicate plastic loading significantly weakens the anisotropic SRA behavior,owing to numerous uniformly distributed fine T1phases and small IPA values of both T1precipitates size and PFZ width in various loading directions.Compared with those of elastic loadingaged alloys,yield strength of plastic loading-aged alloys shows high strength-ductility because of the combined effect of closely dispersed fine T1precipitates,narrowed PFZ and numerous sheared and rotated T1phases at different locations during tensile process.The uniformly distributed larger Kernel Average Misorientation(KAM)and Schmidt factor values of the plastic loading-aged alloy,as well as the cross-slip generated,also help to enhance the strength and ductility of the alloy.展开更多
In this work,the aging response and mechanism of dual-phase Mg-Li-Al-Zn alloy at various temperatures are investigated.The results show that the strengthening after quenching is primarily attributed to the immediate p...In this work,the aging response and mechanism of dual-phase Mg-Li-Al-Zn alloy at various temperatures are investigated.The results show that the strengthening after quenching is primarily attributed to the immediate precipitation of the semi-coherent~Mg_(3)Zn phase.The aging softening of the studied alloy is mainly caused by the rapid transformation of the strengthening~Mg_(3)Zn phase to the softening MgLi(Al,Zn)phase,along with the coarsening of theα-Mg matrix and precipitates withinβ-Li matrix.Further analysis indicates that the quick precipitation and transformation of~Mg_(3)Zn is a consequence of the high diffusion rate of solute atoms,resulting from dense vacancy concentration in theβ-Li matrix.This research bridges a critical gap in the study of aging mechanism in the dual-phase Mg-Li-Al-Zn alloy,providing a theoretical basis for the development and application of high-performance and thermal-stable Mg-Li alloys.展开更多
Alzheimer’s disease(AD)is a neurodegenerative disorder associated with brain aging,and the accumulation ofβ-amyloid(Aβ)and hyperphosphorylated Tau proteins are key pathological features.Currently,drugs for the trea...Alzheimer’s disease(AD)is a neurodegenerative disorder associated with brain aging,and the accumulation ofβ-amyloid(Aβ)and hyperphosphorylated Tau proteins are key pathological features.Currently,drugs for the treatment of AD are mainly single-targeted,but the complex pathogenesis of AD makes it difficult to achieve the desired results.Therefore,the development of multitargeted therapies is crucial for future interventions.Rice bran oil(RBO)has been recognized as an edible oil with several health benefits,but its effects on AD caused by brain aging remain underexplored.In this study,the effects of RBO on memory dysfunction in D-galactose(D-gal)mice and its molecular mechanisms were investigated via in vivo and in silico methods from the perspective of AD pathologies.Our results suggested that compounds in RBO could modulate the activities of Aβprecursor protein cleaving enzyme 1(BACE1),mitogen-activated protein kinase 3(MAPK3),matrix metalloproteinase 3(MMP3),and intercellular adhesion molecule 1(ICAM1),leading to inhibition of Aβaccumulation and Tau protein hyperphosphorylation.Moreover,RBO reduced Aβ-induced oxidative stress by inhibiting the activity of mouse double minute 2 homolog(MDM2)and cyclic adenosine monophosphate(cAMP)response element binding protein binding protein(CREBBP),and attenuated neuroinflammation by inhibiting the activity of nitric oxide synthase 2(NOS2)and reducing Aβaccumulation and Tau protein hyperphosphorylation.Additionally,α-linolenic acid in RBO exhibited inhibitory effects on D-gal-induced apoptosis in PC12 cells through modulation of NOS2,MDM2,ICAM1,and phospho-extracellular signal-regulated kinase 1/2(p-ERK1/2).Similarly,stigmastanol inhibited apoptosis in D-gal-induced PC12 cells through the regulation of NOS2.Thus,RBO can be considered as a potential functional food to attenuate AD owing to its multicomponent and multitarget effects.展开更多
A new unified constitutive model was developed to predict the two-stage creep-aging(TSCA)behavior of Al-Zn-Mg-Cu alloys.The particular bimodal precipitation feature was analyzed and modeled by considering the primary ...A new unified constitutive model was developed to predict the two-stage creep-aging(TSCA)behavior of Al-Zn-Mg-Cu alloys.The particular bimodal precipitation feature was analyzed and modeled by considering the primary micro-variables evolution at different temperatures and their interaction.The dislocation density was incorporated into the model to capture the effect of creep deformation on precipitation.Quantitative transmission electron microscopy and experimental data obtained from a previous study were used to calibrate the model.Subsequently,the developed constitutive model was implemented in the finite element(FE)software ABAQUS via the user subroutines for TSCA process simulation and the springback prediction of an integral panel.A TSCA test was performed.The result shows that the maximum radius deviation between the formed plate and the simulation results is less than 0.4 mm,thus validating the effectiveness of the developed constitutive model and FE model.展开更多
The complex morphological,anatomical,physiological,and chemical mechanisms within the aging brain have been the hot topic of research for centuries.The aging process alters the brain structure that affects functions a...The complex morphological,anatomical,physiological,and chemical mechanisms within the aging brain have been the hot topic of research for centuries.The aging process alters the brain structure that affects functions and cognitions,but the worsening of such processes contributes to the pathogenesis of neurodegenerative disorders,such as Alzheimer's disease.Beyond these observable,mild morphological shifts,significant functional modifications in neurotransmission and neuronal activity critically influence the aging brain.Understanding these changes is important for maintaining cognitive health,especially given the increasing prevalence of age-related conditions that affect cognition.This review aims to explore the age-induced changes in brain plasticity and molecular processes,differentiating normal aging from the pathogenesis of Alzheimer's disease,thereby providing insights into predicting the risk of dementia,particularly Alzheimer's disease.展开更多
The neuromuscular junction(NMJ)is an essential synaptic structure composed of motor neurons,skeletal muscles,and glial cells that orchestrate the critical process of muscle contraction(Li et al.,2018).The typical NMJ ...The neuromuscular junction(NMJ)is an essential synaptic structure composed of motor neurons,skeletal muscles,and glial cells that orchestrate the critical process of muscle contraction(Li et al.,2018).The typical NMJ structure is classically described as having a“pretzel-like”shape in mice(Figure 1),whereas human NMJs have a smaller,fragmented structure throughout adulthood.Degenerated NMJs exhibit smaller or fragmented endplates,partial denervation,reduced numbers of synaptic vesicles,abnormal presynaptic mitochondria,and dysfunctional perisynaptic Schwann cells(Alhindi et al.,2022).展开更多
“Last scene of all that ends this strange,eventful history,is second childishness and mere oblivion.I am sans teeth,sans eyes,sans taste,sans everything.”William Shakespeare‘As You Like It'Act 2,Sc.7,l.139Aging...“Last scene of all that ends this strange,eventful history,is second childishness and mere oblivion.I am sans teeth,sans eyes,sans taste,sans everything.”William Shakespeare‘As You Like It'Act 2,Sc.7,l.139Aging of the human brain is characterized by a progressive decline of its functional capacity;this decline however varies widely,and cognitive longevity differs substantially between individuals.展开更多
The microstructure,micro-hardness,and tensile properties of interface between hot isostatic pressing densified low alloy steel and Inconel 690 cladding were investigated during the aging process at 600℃.The results s...The microstructure,micro-hardness,and tensile properties of interface between hot isostatic pressing densified low alloy steel and Inconel 690 cladding were investigated during the aging process at 600℃.The results show that the interface region can be divided into four zones from base metal to deposited metal:carbon-depleted zone(CDZ),partial melting zone(PMZ),planar growth zone(PGZ),and brownish feature zone(BFZ).Dimensions of these zones do not significantly change during aging.However,type I carbides noticeably increase in size in the PMZ,and precipitates clearly occur in the PGZ.The main reason for their growth and occurrence is continuous carbon migration.The highest micro-hardness appears in the PGZ and BFZ regions,which is related to carbon accumulation and precipitates in these regions.Tensile failure occurs on the base metal side due to the high strength mismatch between these two materials.The CDZ,composed of only ferrite,has lower strength and fractures at the boundary between CDZ and base metal.The ultimate tensile strength decreases by only 50 MPa after aging for 1500 h,and the interface region maintains high strength without significant deformation.展开更多
The effects of different aging processes on the precipitated phase,mechanical properties,molten salt corrosion resistance and post-weld microstructure of 347H stainless steel were studied.The results show that a large...The effects of different aging processes on the precipitated phase,mechanical properties,molten salt corrosion resistance and post-weld microstructure of 347H stainless steel were studied.The results show that a large number of precipitated phases appear in the crystal after aging at 700℃for 400 h.After aging for 3000 h,the number of precipitated phases increases and most of them are gathered at the grain boundaries.There are two forms of precipitates,one is the coarse precipitate rich in Cr,and the other is the smaller precipitates mainly consisting of NbC.After aging at 700℃for 30 min,the yield strength and tensile strength of the samples at room temperature and 593℃increase,but the elongation decreases.The corrosion results in nitrate at 565℃show that the corrosion products of the aged samples are the same as that of the original samples,which are Fe_(2)O_(3),Fe_(3)O_(4),MgCr_(2)O_(4),MgFe_(2)O_(4),FeCr_(2)O_(4) and NaFeO_(2).The proportion of Fe_(3)O_(4) that is dense and well bonded to the subtrate in the original sample is higher than that in the aged sample,so the corrosion resistance is better.At 700℃,the aging time has no obvious effect on the microstructure after welding.展开更多
Self-designed Al8Si0.4Mg0.4Fe aluminium alloy was modified with Sr,followed by solid solution and aging treatments to regulate its microstructure and mechanical/electrical properties.The results show that after the mo...Self-designed Al8Si0.4Mg0.4Fe aluminium alloy was modified with Sr,followed by solid solution and aging treatments to regulate its microstructure and mechanical/electrical properties.The results show that after the modification treatment,the room-temperature tensile strength of the alloy remains nearly unchanged,the elongation at break slightly increases from 1.82%to 3.34%,and the electrical conductivity significantly increases from 40.1%international annealed copper standard(IACS)to 42.0%IACS.After the modification,the alloy was subjected to solid solution treatment at 515℃for 8 h,followed by aging treatment at 180,200,220 and 240℃for 6 h.With increasing aging temperature,the electrical conductivity increases monotonously from 41.4%IACS to 45.5%IACS,while the room-temperature tensile strength initially increases and then decreases.At 200℃,the alloy achieves an optimal balance between electrical conductivity and room-temperature tensile strength:the electrical conductivity is 42.5%IACS,and the room-temperature tensile strength is 282.9 MPa.When the aging temperature continues to rise,the alloy undergoes overaging.Although the conductivity continues to increase,the room-temperature tensile strength drops sharply,and it is only 177.1 MPa at 240℃.展开更多
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).
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.
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.
基金Supported by the Wuxi Municipal Health Commission Major Project,No.Z202107。
文摘BACKGROUND Successful aging(SA)refers to the ability to maintain high levels of physical,cognitive,psychological,and social engagement in old age,with high cognitive function being the key to achieving SA.AIM To explore the potential characteristics of the brain network and functional connectivity(FC)of SA.METHODS Twenty-six SA individuals and 47 usual aging individuals were recruited from community-dwelling elderly,which were taken the magnetic resonance imaging scan and the global cognitive function assessment by Mini Mental State Examination(MMSE).The resting state-functional magnetic resonance imaging data were preprocessed by DPABISurf,and the brain functional network was conducted by DPABINet.The support vector machine model was constructed with altered functional connectivities to evaluate the identification value of SA.RESULTS The results found that the 6 inter-network FCs of 5 brain networks were significantly altered and related to MMSE performance.The FC of the right orbital part of the middle frontal gyrus and right angular gyrus was mostly increased and positively related to MMSE score,and the FC of the right supramarginal gyrus and right temporal pole:Middle temporal gyrus was the only one decreased and negatively related to MMSE score.All 17 significantly altered FCs of SA were taken into the support vector machine model,and the area under the curve was 0.895.CONCLUSION The identification of key brain networks and FC of SA could help us better understand the brain mechanism and further explore neuroimaging biomarkers of SA.
基金supported by the Key Projects of Medical Science and Technology of Henan Province,No.SBGJ202002099(to JY)。
文摘Regulated cell death(such as apoptosis,necroptosis,pyroptosis,autophagy,cuproptosis,ferroptosis,disulfidptosis)involves complex signaling pathways and molecular effectors,and has been proven to be an important regulatory mechanism for regulating neuronal aging and death.However,excessive activation of regulated cell death may lead to the progression of aging-related diseases.This review summarizes recent advances in the understanding of seven forms of regulated cell death in age-related diseases.Notably,the newly identified ferroptosis and cuproptosis have been implicated in the risk of cognitive impairment and neurodegenerative diseases.These forms of cell death exacerbate disease progression by promoting inflammation,oxidative stress,and pathological protein aggregation.The review also provides an overview of key signaling pathways and crosstalk mechanisms among these regulated cell death forms,with a focus on ferroptosis,cuproptosis,and disulfidptosis.For instance,FDX1 directly induces cuproptosis by regulating copper ion valency and dihydrolipoamide S-acetyltransferase aggregation,while copper mediates glutathione peroxidase 4 degradation,enhancing ferroptosis sensitivity.Additionally,inhibiting the Xc-transport system to prevent ferroptosis can increase disulfide formation and shift the NADP^(+)/NADPH ratio,transitioning ferroptosis to disulfidptosis.These insights help to uncover the potential connections among these novel regulated cell death forms and differentiate them from traditional regulated cell death mechanisms.In conclusion,identifying key targets and their crosstalk points among various regulated cell death pathways may aid in developing specific biomarkers to reverse the aging clock and treat age-related neurodegenerative conditions.
基金supported by the National Natural Science Foundation of China,No.81921006(to GHL)。
文摘The oral cavity is a complex physiological community encompassing a wide range of microorganisms.Dysbiosis of oral microbiota can lead to various oral infectious diseases,such as periodontitis and tooth decay,and even affect systemic health,including brain aging and neurodegenerative diseases.Recent studies have highlighted how oral microbes might be involved in brain aging and neurodegeneration,indicating potential avenues for intervention strategies.In this review,we summarize clinical evidence demonstrating a link between oral microbes/oral infectious diseases and brain aging/neurodegenerative diseases,and dissect potential mechanisms by which oral microbes contribute to brain aging and neurodegeneration.We also highlight advances in therapeutic development grounded in the realm of oral microbes,with the goal of advancing brain health and promoting healthy aging.
基金funded by CONAHCYT grant(252808)to GFCONAHCYT’s“Estancias Posdoctorales por México”program(662350)to HTB。
文摘Recent reports suggest that aging is not solely a physiological process in living beings;instead, it should be considered a pathological process or disease(Amorim et al., 2022). Consequently, this process involves a wide range of factors, spanning from genetic to environmental factors, and even includes the gut microbiome(GM)(Mayer et al., 2022). All these processes coincide at some point in the inflammatory process, oxidative stress, and apoptosis, at different degrees in various organs and systems that constitute a living organism(Mayer et al., 2022;AguilarHernández et al., 2023).
基金financially supported by the National Natural Science Foundation of China(No.52071040 and 51871036)Natural Science Foundation of Shandong Province,China(No.ZR2022QE008)China Postdoctoral Science Foundation(No.2022M712984)。
文摘Although magnesium-aluminum alloys,such as AZ80 and AZ91 have promising application potential in automotive,high-speed train and aerospace fields,their age-hardening response is generally not very appreciable.In this work,the aging-hardening response of AZ80 alloy was effectively enhanced by applying cold-rolling deformation before conducting conventional aging treatment at 200°C.Compared to the directly aged sample,the yield strength of the pre-rolling and aged sample was increased by 35 MPa.Electron microscope examination confirmed that profuse{10¯11}and{10¯11}-{10¯12}twins,consisting of high density of dislocations and stacking faults,were generated by cold rolling.Blocky or ellipsoidal Mg_(17)Al_(12)precipitates formed at the twin boundaries(TBs)during subsequent aging treatment.Crystallographic analysis indicated that the precipitates at{10¯11}TBs always held an identical Potter OR with both the matrix and twin,while the precipitates at{10¯11}-{10¯12}TBs exhibited three different ORs:Burgers OR,Potter OR and P-S OR with either the matrix or the twin.Moreover,recrystallized grains were found inside{10¯11}-{10¯12}double twins after peak-aging at 200°C,implying that precipitation and recrystallization might occur concurrently along TBs at a relatively low temperature.It was speculated that the highly stored energy inside twins and the high elastic energy between the precipitates and twins were driving factors for the occurrence of recrystallization.
基金support from the Key Program of the National Natural Science Foundation of China(No.51235010)。
文摘Although the plastic loading can enhance creep deformation and yield strength,the anisotropic Stress Relaxation Aging(SRA)behavior and mechanism under plastic loading remain unclear,which presents a significant challenge in accurately shaping aluminum alloy panels.In this study,the SRA behavior of 2195-T4 Al-Cu-Li alloys were thoroughly studied under initial loading stresses within the elastic(210/250 MPa)and plastic(380/420 MPa)ranges at 180℃by stress relaxation and tensile tests as well as microstructure characterization.The findings reveal that compared with those under elastic loadings,in-plane anisotropy(IPA)values of the stress relaxation amount,yield strength and fracture elongation under plastic loadings are reduced by 60%–80%,70%–90% and 72%–89%,respectively.Similarly,IPA values of precipitate size in grains and PrecipitationFree Zones(PFZ)width at grain boundaries under plastic loading decrease by 31.4%and 94.4%respectively.These results indicate plastic loading significantly weakens the anisotropic SRA behavior,owing to numerous uniformly distributed fine T1phases and small IPA values of both T1precipitates size and PFZ width in various loading directions.Compared with those of elastic loadingaged alloys,yield strength of plastic loading-aged alloys shows high strength-ductility because of the combined effect of closely dispersed fine T1precipitates,narrowed PFZ and numerous sheared and rotated T1phases at different locations during tensile process.The uniformly distributed larger Kernel Average Misorientation(KAM)and Schmidt factor values of the plastic loading-aged alloy,as well as the cross-slip generated,also help to enhance the strength and ductility of the alloy.
基金supported by the Foundation Strengthening Plan Technical Field Fund(No.2021-JJ-0112)Major Scientific and Technological Innovation Project of Luoyang(No.2201029A)+1 种基金National Science and Technology Innovation Special Zone(No.02-14-01)National Natural Science Foundation of China(No.U2037601).
文摘In this work,the aging response and mechanism of dual-phase Mg-Li-Al-Zn alloy at various temperatures are investigated.The results show that the strengthening after quenching is primarily attributed to the immediate precipitation of the semi-coherent~Mg_(3)Zn phase.The aging softening of the studied alloy is mainly caused by the rapid transformation of the strengthening~Mg_(3)Zn phase to the softening MgLi(Al,Zn)phase,along with the coarsening of theα-Mg matrix and precipitates withinβ-Li matrix.Further analysis indicates that the quick precipitation and transformation of~Mg_(3)Zn is a consequence of the high diffusion rate of solute atoms,resulting from dense vacancy concentration in theβ-Li matrix.This research bridges a critical gap in the study of aging mechanism in the dual-phase Mg-Li-Al-Zn alloy,providing a theoretical basis for the development and application of high-performance and thermal-stable Mg-Li alloys.
基金supported by the Science and Technology Innovation Program of Hunan Province(2022RC1148)the Natural Science Foundation of Hunan Province(2022JJ31009,2022JJ50260)+4 种基金the Program for Science and Technology of Changsha,China(kh2301028)the Science and Technology Innovation Plan Project of Hunan Province(2023NK2033)the Innovation Leading Plan Project of Hunan Province(2021GK4022)the“Kemen Food”Graduate Science and Technology Innovation Project of Central South University of Forestry and Technology(2023KMCX02)the Graduate Science and Technology Innovation Fund Project of Hunan Province(QL20220182).
文摘Alzheimer’s disease(AD)is a neurodegenerative disorder associated with brain aging,and the accumulation ofβ-amyloid(Aβ)and hyperphosphorylated Tau proteins are key pathological features.Currently,drugs for the treatment of AD are mainly single-targeted,but the complex pathogenesis of AD makes it difficult to achieve the desired results.Therefore,the development of multitargeted therapies is crucial for future interventions.Rice bran oil(RBO)has been recognized as an edible oil with several health benefits,but its effects on AD caused by brain aging remain underexplored.In this study,the effects of RBO on memory dysfunction in D-galactose(D-gal)mice and its molecular mechanisms were investigated via in vivo and in silico methods from the perspective of AD pathologies.Our results suggested that compounds in RBO could modulate the activities of Aβprecursor protein cleaving enzyme 1(BACE1),mitogen-activated protein kinase 3(MAPK3),matrix metalloproteinase 3(MMP3),and intercellular adhesion molecule 1(ICAM1),leading to inhibition of Aβaccumulation and Tau protein hyperphosphorylation.Moreover,RBO reduced Aβ-induced oxidative stress by inhibiting the activity of mouse double minute 2 homolog(MDM2)and cyclic adenosine monophosphate(cAMP)response element binding protein binding protein(CREBBP),and attenuated neuroinflammation by inhibiting the activity of nitric oxide synthase 2(NOS2)and reducing Aβaccumulation and Tau protein hyperphosphorylation.Additionally,α-linolenic acid in RBO exhibited inhibitory effects on D-gal-induced apoptosis in PC12 cells through modulation of NOS2,MDM2,ICAM1,and phospho-extracellular signal-regulated kinase 1/2(p-ERK1/2).Similarly,stigmastanol inhibited apoptosis in D-gal-induced PC12 cells through the regulation of NOS2.Thus,RBO can be considered as a potential functional food to attenuate AD owing to its multicomponent and multitarget effects.
基金supported by the National Key R&D Program of China(No.2021YFB3400900)the National Natural Science Foundation of China(Nos.52175373,52205435)+1 种基金Natural Science Foundation of Hunan Province,China(No.2022JJ40621)the Innovation Fund of National Commercial Aircraft Manufacturing Engineering Technology Center,China(No.COMACSFGS-2022-1875)。
文摘A new unified constitutive model was developed to predict the two-stage creep-aging(TSCA)behavior of Al-Zn-Mg-Cu alloys.The particular bimodal precipitation feature was analyzed and modeled by considering the primary micro-variables evolution at different temperatures and their interaction.The dislocation density was incorporated into the model to capture the effect of creep deformation on precipitation.Quantitative transmission electron microscopy and experimental data obtained from a previous study were used to calibrate the model.Subsequently,the developed constitutive model was implemented in the finite element(FE)software ABAQUS via the user subroutines for TSCA process simulation and the springback prediction of an integral panel.A TSCA test was performed.The result shows that the maximum radius deviation between the formed plate and the simulation results is less than 0.4 mm,thus validating the effectiveness of the developed constitutive model and FE model.
文摘The complex morphological,anatomical,physiological,and chemical mechanisms within the aging brain have been the hot topic of research for centuries.The aging process alters the brain structure that affects functions and cognitions,but the worsening of such processes contributes to the pathogenesis of neurodegenerative disorders,such as Alzheimer's disease.Beyond these observable,mild morphological shifts,significant functional modifications in neurotransmission and neuronal activity critically influence the aging brain.Understanding these changes is important for maintaining cognitive health,especially given the increasing prevalence of age-related conditions that affect cognition.This review aims to explore the age-induced changes in brain plasticity and molecular processes,differentiating normal aging from the pathogenesis of Alzheimer's disease,thereby providing insights into predicting the risk of dementia,particularly Alzheimer's disease.
基金funded by the Japan Society for the Promotion of Science,JSPS,23K07290(to MF).
文摘The neuromuscular junction(NMJ)is an essential synaptic structure composed of motor neurons,skeletal muscles,and glial cells that orchestrate the critical process of muscle contraction(Li et al.,2018).The typical NMJ structure is classically described as having a“pretzel-like”shape in mice(Figure 1),whereas human NMJs have a smaller,fragmented structure throughout adulthood.Degenerated NMJs exhibit smaller or fragmented endplates,partial denervation,reduced numbers of synaptic vesicles,abnormal presynaptic mitochondria,and dysfunctional perisynaptic Schwann cells(Alhindi et al.,2022).
文摘“Last scene of all that ends this strange,eventful history,is second childishness and mere oblivion.I am sans teeth,sans eyes,sans taste,sans everything.”William Shakespeare‘As You Like It'Act 2,Sc.7,l.139Aging of the human brain is characterized by a progressive decline of its functional capacity;this decline however varies widely,and cognitive longevity differs substantially between individuals.
基金Major Scientific and Technological Project of Gansu(22ZD6GA008)Excellent Doctorate Project of Gansu(23JRRA806)National Natural Science Foundation of China(52175325,51961024,52071170)。
文摘The microstructure,micro-hardness,and tensile properties of interface between hot isostatic pressing densified low alloy steel and Inconel 690 cladding were investigated during the aging process at 600℃.The results show that the interface region can be divided into four zones from base metal to deposited metal:carbon-depleted zone(CDZ),partial melting zone(PMZ),planar growth zone(PGZ),and brownish feature zone(BFZ).Dimensions of these zones do not significantly change during aging.However,type I carbides noticeably increase in size in the PMZ,and precipitates clearly occur in the PGZ.The main reason for their growth and occurrence is continuous carbon migration.The highest micro-hardness appears in the PGZ and BFZ regions,which is related to carbon accumulation and precipitates in these regions.Tensile failure occurs on the base metal side due to the high strength mismatch between these two materials.The CDZ,composed of only ferrite,has lower strength and fractures at the boundary between CDZ and base metal.The ultimate tensile strength decreases by only 50 MPa after aging for 1500 h,and the interface region maintains high strength without significant deformation.
基金Science and Technology Program Project of Gansu Province(21ZD3GB001)。
文摘The effects of different aging processes on the precipitated phase,mechanical properties,molten salt corrosion resistance and post-weld microstructure of 347H stainless steel were studied.The results show that a large number of precipitated phases appear in the crystal after aging at 700℃for 400 h.After aging for 3000 h,the number of precipitated phases increases and most of them are gathered at the grain boundaries.There are two forms of precipitates,one is the coarse precipitate rich in Cr,and the other is the smaller precipitates mainly consisting of NbC.After aging at 700℃for 30 min,the yield strength and tensile strength of the samples at room temperature and 593℃increase,but the elongation decreases.The corrosion results in nitrate at 565℃show that the corrosion products of the aged samples are the same as that of the original samples,which are Fe_(2)O_(3),Fe_(3)O_(4),MgCr_(2)O_(4),MgFe_(2)O_(4),FeCr_(2)O_(4) and NaFeO_(2).The proportion of Fe_(3)O_(4) that is dense and well bonded to the subtrate in the original sample is higher than that in the aged sample,so the corrosion resistance is better.At 700℃,the aging time has no obvious effect on the microstructure after welding.
基金Applied Basic Research Program of Liaoning Province(CN)(2022JH2/101300078)。
文摘Self-designed Al8Si0.4Mg0.4Fe aluminium alloy was modified with Sr,followed by solid solution and aging treatments to regulate its microstructure and mechanical/electrical properties.The results show that after the modification treatment,the room-temperature tensile strength of the alloy remains nearly unchanged,the elongation at break slightly increases from 1.82%to 3.34%,and the electrical conductivity significantly increases from 40.1%international annealed copper standard(IACS)to 42.0%IACS.After the modification,the alloy was subjected to solid solution treatment at 515℃for 8 h,followed by aging treatment at 180,200,220 and 240℃for 6 h.With increasing aging temperature,the electrical conductivity increases monotonously from 41.4%IACS to 45.5%IACS,while the room-temperature tensile strength initially increases and then decreases.At 200℃,the alloy achieves an optimal balance between electrical conductivity and room-temperature tensile strength:the electrical conductivity is 42.5%IACS,and the room-temperature tensile strength is 282.9 MPa.When the aging temperature continues to rise,the alloy undergoes overaging.Although the conductivity continues to increase,the room-temperature tensile strength drops sharply,and it is only 177.1 MPa at 240℃.
