SKI family transcriptional corepressor 1(SKOR1also known as LbxCor1, Fussel15, or CORL1), is a member of the SKI family of proteins and is transcribed from a protein-coding gene located on chromosome 15 in humans, tha...SKI family transcriptional corepressor 1(SKOR1also known as LbxCor1, Fussel15, or CORL1), is a member of the SKI family of proteins and is transcribed from a protein-coding gene located on chromosome 15 in humans, that has a molecular weight of approximately 100 kDa. Skor1 is highly expressed in neurons in the central nervous system of both humans and rodents.展开更多
Mitochondrial dysfunction and oxidative stress are widely regarded as primary drivers of aging and are associated with several neurodegenerative diseases.The degeneration of motor neurons during aging is a critical pa...Mitochondrial dysfunction and oxidative stress are widely regarded as primary drivers of aging and are associated with several neurodegenerative diseases.The degeneration of motor neurons during aging is a critical pathological factor contributing to the progression of sarcopenia.However,the morphological and functional changes in mitochondria and their interplay in the degeneration of the neuromuscular junction during aging remain poorly understood.A defined systematic search of the Pub Med,Web of Science and Embase databases(last accessed on October 30,2024)was conducted with search terms including'mitochondria','aging'and'NMJ'.Clinical and preclinical studies of mitochondrial dysfunction and neuromuscular junction degeneration during aging.Twentyseven studies were included in this systematic review.This systematic review provides a summary of morphological,functional and biological changes in neuromuscular junction,mitochondrial morphology,biosynthesis,respiratory chain function,and mitophagy during aging.We focus on the interactions and mechanisms underlying the relationship between mitochondria and neuromuscular junctions during aging.Aging is characterized by significant reductions in mitochondrial fusion/fission cycles,biosynthesis,and mitochondrial quality control,which may lead to neuromuscular junction dysfunction,denervation and poor physical performance.Motor nerve terminals that exhibit redox sensitivity are among the first to exhibit abnormalities,ultimately leading to an early decline in muscle strength through impaired neuromuscular junction transmission function.Parg coactivator 1 alpha is a crucial molecule that regulates mitochondrial biogenesis and modulates various pathways,including the mitochondrial respiratory chain,energy deficiency,oxidative stress,and inflammation.Mitochondrial dysfunction is correlated with neuromuscular junction denervation and acetylcholine receptor fragmentation,resulting in muscle atrophy and a decrease in strength during aging.Physical therapy,pharmacotherapy,and gene therapy can alleviate the structural degeneration and functional deterioration of neuromuscular junction by restoring mitochondrial function.Therefore,mitochondria are considered potential targets for preserving neuromuscular junction morphology and function during aging to treat sarcopenia.展开更多
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
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
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
Two landmark studies demonstrate synergistic approaches to gastrointestinal cancer management.Lin et al identified activin A receptor type 1C polymor-phisms(rs4556933/rs77886248)as esophageal squamous cell carcinoma r...Two landmark studies demonstrate synergistic approaches to gastrointestinal cancer management.Lin et al identified activin A receptor type 1C polymor-phisms(rs4556933/rs77886248)as esophageal squamous cell carcinoma risk modifiers in Chinese Han populations through a case-control study(1264 patients/1361 controls),revealing transforming growth factor-beta pathway-mediated susceptibility in older male smokers(P<0.001).Concurrently,Luo et al established imaging-based differentiation of pancreatic cancer subtypes(pancreatic ductal adenocarcinoma vs neuroendocrine tumors)via retrospective analysis of 500 cases(area under the curve=0.89),enabling earlier intervention.These findings underscore the transformative potential of combining genetic risk stratification with advanced imaging to guide precision screening and therapeutic strategies,addressing critical gaps in esophageal and pancreatic cancer outcomes.展开更多
Reasons causing or accelerating seed aging are mainly damage of mem- branes, DNA and proteins, decline of protein synthesis capacity and excessive ac- cumulation of reactive oxygen species. With the application of nat...Reasons causing or accelerating seed aging are mainly damage of mem- branes, DNA and proteins, decline of protein synthesis capacity and excessive ac- cumulation of reactive oxygen species. With the application of natural aging or artifi- cial aging methods, it was reported that quantitative trait loci （QTLs） of seed stora- bility in rice were widely distributed on the chromosomes except the 10th chromo- some. In this paper, we reviewed the progresses in the research on physiological- biochemical and genetic mechanisms of seed aging, and analyzed the existing problems and developing prospect in molecular breeding of rice with improved seed storability, in order to provide reference for the basic research and genetic improve- ment of rice seed storabUity.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
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
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
The brain has very high energy requirements and consumes 20% of the oxygen and 25% of the glucose in the human body. Therefore, the molecular mechanism under- lying how the brain metabolizes substances to support neur...The brain has very high energy requirements and consumes 20% of the oxygen and 25% of the glucose in the human body. Therefore, the molecular mechanism under- lying how the brain metabolizes substances to support neural activity is a fundamental issue for neuroscience studies. A well-known model in the brain, the astrocyte- neuron lactate shuttle, postulates that glucose uptake and glycolytic activity are enhanced in astrocytes upon neu- ronal activation and that astrocytes transport lactate into neurons to fulfill their energy requirements. Current evidence for this hypothesis has yet to reach a clear consensus, and new concepts beyond the shuttle hypothesis are emerging. The discrepancy is largely attributed to the lack of a critical method for real-time monitoring of metabolic dynamics at cellular resolution. Recent advances in fluorescent protein-based sensors allow the generation of a sensitive, specific, real-time readout of subcellular metabolites and fill the current technological gap. Here,we summarize the development of genetically encoded metabolite sensors and their applications in assessing cell metabolism in living cells and in vivo, and we believe that these tools will help to address the issue of elucidating neural energy metabolism.展开更多
Personality disorders often act as a common denominator for many psychiatric problems,and studies on personality disorders contribute to the etiopathology,diagnosis,and treatment of many mental disorders.In recent yea...Personality disorders often act as a common denominator for many psychiatric problems,and studies on personality disorders contribute to the etiopathology,diagnosis,and treatment of many mental disorders.In recent years,increasing evidence from various studies has shown distinctive features of personality disorders,and that from genetic and neuroimaging studies has been especially valuable.Genetic studies primarily target the genes encoding neurotransmitters and enzymes in the serotoninergic and dopaminergic systems,and neuroimaging studies mainly focus on the frontal and temporal lobes as well as the limbic-paralimbic system in patients with personality disorders.Although some studies have suffered due to unclear diagnoses of personality disorders and some have included few patients for a given personality disorder,great opportunities remain for investigators to launch new ideas and technologies in the field.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
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
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
This article is based on a recent bibliometric analysis of research progress on liver aging.The liver is notable for its extraordinary ability to rejuvenate,thereby safeguarding and maintaining the organism’s integri...This article is based on a recent bibliometric analysis of research progress on liver aging.The liver is notable for its extraordinary ability to rejuvenate,thereby safeguarding and maintaining the organism’s integrity.With advancing age,there is a noteworthy reduction in both the liver’s size and blood circulation.Furthermore,the wide range of physiological alterations driven on by aging may foster the development of illnesses.Previous studies indicate that liver aging is linked to impaired lipid metabolism and abnormal gene expression associated with chronic inflammation.Factors such as mitochondrial dysfunction and telomere shortening accumulate,which may result in increased hepatic steatosis,which impacts liver regeneration,metabolism,and other functions.Knowing the structural and functional changes could help elderly adults delay liver aging.Increasing public awareness of anti-aging interventions is essential.Besides the use of dietary supplements,alterations in lifestyle,including changes in dietary habits and physical exercise routines,are the most efficacious means to decelerate the aging process of the liver.This article highlights recent advances in the mechanism research of liver aging and summarizes the promising intervention options to delay liver aging for preventing related diseases.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
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
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
基金supported by Science Foundation Ireland (Grant 19/FFP/6666),Cure Parkinson’s (Grant CP:GO01)a PhD studentship from the Anatomical Society。
文摘SKI family transcriptional corepressor 1(SKOR1also known as LbxCor1, Fussel15, or CORL1), is a member of the SKI family of proteins and is transcribed from a protein-coding gene located on chromosome 15 in humans, that has a molecular weight of approximately 100 kDa. Skor1 is highly expressed in neurons in the central nervous system of both humans and rodents.
基金supported by grants from Collaborative Research Fund(Ref:C4032-21GF)General Research Grant(Ref:14114822)+1 种基金Group Research Scheme(Ref:3110146)Area of Excellence(Ref:Ao E/M-402/20)。
文摘Mitochondrial dysfunction and oxidative stress are widely regarded as primary drivers of aging and are associated with several neurodegenerative diseases.The degeneration of motor neurons during aging is a critical pathological factor contributing to the progression of sarcopenia.However,the morphological and functional changes in mitochondria and their interplay in the degeneration of the neuromuscular junction during aging remain poorly understood.A defined systematic search of the Pub Med,Web of Science and Embase databases(last accessed on October 30,2024)was conducted with search terms including'mitochondria','aging'and'NMJ'.Clinical and preclinical studies of mitochondrial dysfunction and neuromuscular junction degeneration during aging.Twentyseven studies were included in this systematic review.This systematic review provides a summary of morphological,functional and biological changes in neuromuscular junction,mitochondrial morphology,biosynthesis,respiratory chain function,and mitophagy during aging.We focus on the interactions and mechanisms underlying the relationship between mitochondria and neuromuscular junctions during aging.Aging is characterized by significant reductions in mitochondrial fusion/fission cycles,biosynthesis,and mitochondrial quality control,which may lead to neuromuscular junction dysfunction,denervation and poor physical performance.Motor nerve terminals that exhibit redox sensitivity are among the first to exhibit abnormalities,ultimately leading to an early decline in muscle strength through impaired neuromuscular junction transmission function.Parg coactivator 1 alpha is a crucial molecule that regulates mitochondrial biogenesis and modulates various pathways,including the mitochondrial respiratory chain,energy deficiency,oxidative stress,and inflammation.Mitochondrial dysfunction is correlated with neuromuscular junction denervation and acetylcholine receptor fragmentation,resulting in muscle atrophy and a decrease in strength during aging.Physical therapy,pharmacotherapy,and gene therapy can alleviate the structural degeneration and functional deterioration of neuromuscular junction by restoring mitochondrial function.Therefore,mitochondria are considered potential targets for preserving neuromuscular junction morphology and function during aging to treat sarcopenia.
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.
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Two landmark studies demonstrate synergistic approaches to gastrointestinal cancer management.Lin et al identified activin A receptor type 1C polymor-phisms(rs4556933/rs77886248)as esophageal squamous cell carcinoma risk modifiers in Chinese Han populations through a case-control study(1264 patients/1361 controls),revealing transforming growth factor-beta pathway-mediated susceptibility in older male smokers(P<0.001).Concurrently,Luo et al established imaging-based differentiation of pancreatic cancer subtypes(pancreatic ductal adenocarcinoma vs neuroendocrine tumors)via retrospective analysis of 500 cases(area under the curve=0.89),enabling earlier intervention.These findings underscore the transformative potential of combining genetic risk stratification with advanced imaging to guide precision screening and therapeutic strategies,addressing critical gaps in esophageal and pancreatic cancer outcomes.
基金Supported by Natural Science Foundation of Hainan Province(20163129)
文摘Reasons causing or accelerating seed aging are mainly damage of mem- branes, DNA and proteins, decline of protein synthesis capacity and excessive ac- cumulation of reactive oxygen species. With the application of natural aging or artifi- cial aging methods, it was reported that quantitative trait loci （QTLs） of seed stora- bility in rice were widely distributed on the chromosomes except the 10th chromo- some. In this paper, we reviewed the progresses in the research on physiological- biochemical and genetic mechanisms of seed aging, and analyzed the existing problems and developing prospect in molecular breeding of rice with improved seed storability, in order to provide reference for the basic research and genetic improve- ment of rice seed storabUity.
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supported by the National Key Research and Development Program of China(2017YFA050400 and2017YFC0906900)the National Natural Science Foundation of China(31722033,91649123,31671484,31225008,and 31470833)+4 种基金the Shanghai Science and Technology Commission(14XD1401400,16430723100,and 15YF1402600)Young Elite Scientists Sponsorship Program by China Association for Science and Technology(to YZ)Shanghai Young Top-notch Talent(to YZ)the State Key Laboratory of Bioreactor Engineering(to YY)Fundamental Research Funds for the Central Universities(to YY and YZ)
文摘The brain has very high energy requirements and consumes 20% of the oxygen and 25% of the glucose in the human body. Therefore, the molecular mechanism under- lying how the brain metabolizes substances to support neural activity is a fundamental issue for neuroscience studies. A well-known model in the brain, the astrocyte- neuron lactate shuttle, postulates that glucose uptake and glycolytic activity are enhanced in astrocytes upon neu- ronal activation and that astrocytes transport lactate into neurons to fulfill their energy requirements. Current evidence for this hypothesis has yet to reach a clear consensus, and new concepts beyond the shuttle hypothesis are emerging. The discrepancy is largely attributed to the lack of a critical method for real-time monitoring of metabolic dynamics at cellular resolution. Recent advances in fluorescent protein-based sensors allow the generation of a sensitive, specific, real-time readout of subcellular metabolites and fill the current technological gap. Here,we summarize the development of genetically encoded metabolite sensors and their applications in assessing cell metabolism in living cells and in vivo, and we believe that these tools will help to address the issue of elucidating neural energy metabolism.
基金supported by a grant from the Natural Science Foundation of China (91132715)
文摘Personality disorders often act as a common denominator for many psychiatric problems,and studies on personality disorders contribute to the etiopathology,diagnosis,and treatment of many mental disorders.In recent years,increasing evidence from various studies has shown distinctive features of personality disorders,and that from genetic and neuroimaging studies has been especially valuable.Genetic studies primarily target the genes encoding neurotransmitters and enzymes in the serotoninergic and dopaminergic systems,and neuroimaging studies mainly focus on the frontal and temporal lobes as well as the limbic-paralimbic system in patients with personality disorders.Although some studies have suffered due to unclear diagnoses of personality disorders and some have included few patients for a given personality disorder,great opportunities remain for investigators to launch new ideas and technologies in the field.
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 National Natural Science Foundation of China,No.82104525Open Foundation of Key Laboratory of Tropical Plant Resource Chemistry of Hainan Province,No.rdzw2024s01.
文摘This article is based on a recent bibliometric analysis of research progress on liver aging.The liver is notable for its extraordinary ability to rejuvenate,thereby safeguarding and maintaining the organism’s integrity.With advancing age,there is a noteworthy reduction in both the liver’s size and blood circulation.Furthermore,the wide range of physiological alterations driven on by aging may foster the development of illnesses.Previous studies indicate that liver aging is linked to impaired lipid metabolism and abnormal gene expression associated with chronic inflammation.Factors such as mitochondrial dysfunction and telomere shortening accumulate,which may result in increased hepatic steatosis,which impacts liver regeneration,metabolism,and other functions.Knowing the structural and functional changes could help elderly adults delay liver aging.Increasing public awareness of anti-aging interventions is essential.Besides the use of dietary supplements,alterations in lifestyle,including changes in dietary habits and physical exercise routines,are the most efficacious means to decelerate the aging process of the liver.This article highlights recent advances in the mechanism research of liver aging and summarizes the promising intervention options to delay liver aging for preventing related diseases.
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.
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.
