Aging is a natural lifelong process ending in death. Many older people are living in poverty. Older people are generally considered dependent on others as they grow older. The purpose of this article is to explore the...Aging is a natural lifelong process ending in death. Many older people are living in poverty. Older people are generally considered dependent on others as they grow older. The purpose of this article is to explore the entrepreneurship activities of Nepalese older adults. Data for this study were collected from the project Help Age International (HAI) implemented in Nepal. Qualitative data observations and interviews were used to collect data. The findings of this study show the formation of the Older People’s Association (OPA) has supported many older people to participate outside the home in various social activities. Moreover, regular deposits through OPAs offer little help. OPAs support older people in their need of financial support to implement minor entrepreneurship. Older people who received support were pleased and were actively involved in their activities and also regularly deposited money in them. Subsequently, older people’s participation in social activities has increased and also helped to lower elderly abuse, loneliness, and depression. Local governments should promote such activities which will help with healthy aging.展开更多
Depression is a major health problem, especially for elderly people. According to the “homocysteine hypothesis of depression”, high homocysteine levels may cause depression of mood via cerebrovascular diseases. Whil...Depression is a major health problem, especially for elderly people. According to the “homocysteine hypothesis of depression”, high homocysteine levels may cause depression of mood via cerebrovascular diseases. Whilst biologically plausible, such hypothesis needs yet confirmation. We aimed at: 1) studying the relationships between homocysteinemia (HCY) and depression in a community-dwelling cohort of people aged 70 to 75 years at baseline;2) investigating plasma levels of HCY and 3) comparing these levels between males and females, in the same population. We exploited the data from four waves (2010, 2012, 2014 and 2018) of the longitudinal study “InveCeAb”, with specific regard towards mood assessment, by Geriatric Depression Scale (GDS) scoring, and diagnosis of clinically relevant or subthreshold depression. HCY plasma levels were measured in the waves 2012, 2014 and 2018. Sample attrition was due mainly to death or overall worsening. No statistically significant differences were found in plasma homocysteine levels in each wave, according to depressive symptoms. No correlations were found between plasma HCY levels in each wave with their corresponding GDS scores, even after adjustment for folate and cobalamin blood concentrations. Dichotomized levels of HCY (≤15 vs >15 μM/l) were not associated with dichotomized GDS scores (≤4 vs higher), clinically relevant and subthreshold depression diagnosis and any antidepressive use, in any wave. First (2012) HCY levels increased with participants’ increasing age, cross-sectionally. Listwise HCY concentrations decreased along the 3 waves. HCY levels were always higher in males than in females. Our results may challenge the “homocysteine hypothesis” of depression, whilst supporting the role of high homocysteinemia as a marker of overall bad health.展开更多
Epigenetic regulation of aging:Aging is defined as the gradual decline of physiological function and cellular integrity,causing o rganismal vulnerability to age-onset diseases and morbidity.Studies in different animal...Epigenetic regulation of aging:Aging is defined as the gradual decline of physiological function and cellular integrity,causing o rganismal vulnerability to age-onset diseases and morbidity.Studies in different animal models have led to the identification of twelve aging hallmarks that shared several features:its age-associated manifestation.展开更多
Modern neuroscience began from all reaching and fierce conflict between“neuronismo and reticulismo”——between neuronal and reticular theories of the organization of the nervous system;the conflict culminated in Dec...Modern neuroscience began from all reaching and fierce conflict between“neuronismo and reticulismo”——between neuronal and reticular theories of the organization of the nervous system;the conflict culminated in December of 1906 in Stockholm where Santiago Ramon y Cajal(the proponent of the neuronal doctrine)and Camillo Golgi(who advocated the syncytial reticular organization of neural networks)delivered their Noble prize lectures(Verkhratsky,2009).展开更多
As the life expectancy of the world’s population increases,age-related diseases are emerging as one of the greatest problems facing modern society.The onset of dementia and neurodegenerative diseases is strictly depe...As the life expectancy of the world’s population increases,age-related diseases are emerging as one of the greatest problems facing modern society.The onset of dementia and neurodegenerative diseases is strictly dependent on aging as a major risk factor and has a profound impact on various aspects of the lives of individuals and their families.展开更多
Maillard reaction(MR)is a non-enzymatic browning reaction commonly seen in food processing,which occurs between reducing sugars and compounds with amino groups.Despite certain advantages based on Maillard reaction pro...Maillard reaction(MR)is a non-enzymatic browning reaction commonly seen in food processing,which occurs between reducing sugars and compounds with amino groups.Despite certain advantages based on Maillard reaction products(MRPs)found in some food for health and storage application have appeared,however,the MR occurring in human physiological environment can produce advanced glycation end products(AGEs)by non-enzymatic modification of macromolecules such as proteins,lipids and nucleic acid,which could change the structure and functional activity of the molecules themselves.In this review,we take AGEs as our main object,on the one hand,discuss physiologic aging,that is,age-dependent covalent cross-linking and modification of proteins such as collagen that occur in eyes and skin containing connective tissue.On the other hand,pathological aging associated with autoimmune and inflammatory diseases,neurodegenerative diseases,diabetes and diabetic nephropathy,cardiovascular diseases and bone degenerative diseases have been mainly proposed.Based on the series of adverse effects of accelerated aging and disease pathologies caused by MRPs,the possible harm caused by some MR can be slowed down or inhibited by artificial drug intervention,dietary pattern and lifestyle control.It also stimulates people's curiosity to continue to explore the potential link between the MR and human aging and health,which should be paid more attention to for the development of life sciences.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 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
Aging is the leading risk factor for Alzheimer’s disease and other neurodegenerative diseases. We now understand that a breakdown in the neuronal cytoskeleton, mainly underpinned by protein modifications leading to t...Aging is the leading risk factor for Alzheimer’s disease and other neurodegenerative diseases. We now understand that a breakdown in the neuronal cytoskeleton, mainly underpinned by protein modifications leading to the destabilization of microtubules, is central to the pathogenesis of Alzheimer’s disease. This is accompanied by morphological defects across the somatodendritic compartment, axon, and synapse. However, knowledge of what occurs to the microtubule cytoskeleton and morphology of the neuron during physiological aging is comparatively poor. Several recent studies have suggested that there is an age-related increase in the phosphorylation of the key microtubule stabilizing protein tau, a modification, which is known to destabilize the cytoskeleton in Alzheimer’s disease. This indicates that the cytoskeleton and potentially other neuronal structures reliant on the cytoskeleton become functionally compromised during normal physiological aging. The current literature shows age-related reductions in synaptic spine density and shifts in synaptic spine conformation which might explain age-related synaptic functional deficits. However, knowledge of what occurs to the microtubular and actin cytoskeleton, with increasing age is extremely limited. When considering the somatodendritic compartment, a regression in dendrites and loss of dendritic length and volume is reported whilst a reduction in soma volume/size is often seen. However, research into cytoskeletal change is limited to a handful of studies demonstrating reductions in and mislocalizations of microtubule-associated proteins with just one study directly exploring the integrity of the microtubules. In the axon, an increase in axonal diameter and age-related appearance of swellings is reported but like the dendrites, just one study investigates the microtubules directly with others reporting loss or mislocalization of microtubule-associated proteins. Though these are the general trends reported, there are clear disparities between model organisms and brain regions that are worthy of further investigation. Additionally, longitudinal studies of neuronal/cytoskeletal aging should also investigate whether these age-related changes contribute not just to vulnerability to disease but also to the decline in nervous system function and behavioral output that all organisms experience. This will highlight the utility, if any, of cytoskeletal fortification for the promotion of healthy neuronal aging and potential protection against age-related neurodegenerative disease. This review seeks to summarize what is currently known about the physiological aging of the neuron and microtubular cytoskeleton in the hope of uncovering mechanisms underpinning age-related risk to disease.展开更多
Background The ovaries are one of the first organs that undergo degenerative changes earlier in the aging process,and ovarian aging is shown by a decrease in the number and quality of oocytes.However,little is known a...Background The ovaries are one of the first organs that undergo degenerative changes earlier in the aging process,and ovarian aging is shown by a decrease in the number and quality of oocytes.However,little is known about the molecular mechanisms of female age-related fertility decline in different types of ovarian cells during aging,especially in goats.Therefore,the aim of this study was to reveal the mechanisms driving ovarian aging in goats at single-cell resolution.Results For the first time,we surveyed the single-cell transcriptomic landscape of over 27,000 ovarian cells from newborn,young and aging goats,and identified nine ovarian cell types with distinct gene-expression signatures.Functional enrichment analysis showed that ovarian cell types were involved in their own unique biological processes,such as Wnt beta-catenin signalling was enriched in germ cells,whereas ovarian steroidogenesis was enriched in granulosa cells(GCs).Further analysis showed that ovarian aging was linked to GCs-specific changes in the antioxidant system,oxidative phosphorylation,and apoptosis.Subsequently,we identified a series of dynamic genes,such as AMH,CRABP2,THBS1 and TIMP1,which determined the fate of GCs.Additionally,FOXO1,SOX4,and HIF1A were identified as significant regulons that instructed the differentiation of GCs in a distinct manner during ovarian aging.Conclusions This study revealed a comprehensive aging-associated transcriptomic atlas characterizing the cell typespecific mechanisms during ovarian aging at the single-cell level and offers new diagnostic biomarkers and potential therapeutic targets for age-related goat ovarian diseases.展开更多
Autophagy is a prosurvival mechanism for the clearance of accumulated abnormal proteins,damaged organelles,and excessive lipids within mammalian cells.A growing body of data indicates that autophagy is reduced in agin...Autophagy is a prosurvival mechanism for the clearance of accumulated abnormal proteins,damaged organelles,and excessive lipids within mammalian cells.A growing body of data indicates that autophagy is reduced in aging cells.This reduction leads to various diseases,such as myocardial hypertrophy,infarction,and atherosclerosis.Recent studies in animal models of an aging heart showed that fasting-induced autophagy improved cardiac function and longevity.This improvement is related to autophagic clearance of damaged cellular components via either bulk or selective autophagy(such as mitophagy).In this editorial,we summarize the mechanisms of autophagy in normal and aging hearts.In addition,the protective effect of fasting-induced autophagy in cardiac aging has been highlighted.展开更多
To study the atmospheric aging of acrylic coatings,a two-year aging exposure experiment was conducted in 13 representative climatic environments in China.An atmospheric aging evaluation model of acrylic coatings was d...To study the atmospheric aging of acrylic coatings,a two-year aging exposure experiment was conducted in 13 representative climatic environments in China.An atmospheric aging evaluation model of acrylic coatings was developed based on aging data including11 environmental factors from 567 cities.A hybrid method of random forest and Spearman correlation analysis was used to reduce the redundancy and multicollinearity of the data set by dimensionality reduction.A semi-supervised collaborative trained regression model was developed with the environmental factors as input and the low-frequency impedance modulus values of the electrochemical impedance spectra of acrylic coatings in 3.5wt%NaCl solution as output.The model improves accuracy compared to supervised learning algorithms model(support vector machines model).The model provides a new method for the rapid evaluation of the aging performance of acrylic coatings,and may also serve as a reference to evaluate the aging performance of other organic coatings.展开更多
Introduction: The stability of orthodontic brackets throughout orthodontic treatment plays a critical role in the treatment’s effectiveness. The present in vitro study was designed to assess the impact of various die...Introduction: The stability of orthodontic brackets throughout orthodontic treatment plays a critical role in the treatment’s effectiveness. The present in vitro study was designed to assess the impact of various dietary components on the performance of orthodontic brackets. Methods: Metal orthodontic brackets were bonded to 66 extracted anterior teeth divided into groups based on the solution type: Milk, Gatorade, Cold Coffee, and a control group using water. Each group consisted of 20 teeth except for the control group, which included six teeth. The bracketed teeth were submerged in their respective solutions for 15 minutes three times daily at different intervals to mimic an in vivo environment and were stored in artificial saliva at room temperature (23?C). The specimens underwent artificial aging through 10,000 cycles of thermocycling (representing one clinical year) between 5?C and 55?C. Shade measurements were taken using a VITA Easy Shade device, capturing the classic shade and L*, a*, and b* values. Delta E values were calculated immediately post-bonding and after 7 days, 1 month, 1, and 2 clinical years. The shear bond strength of each bracket was measured using an ultra-tester machine. Results: After two clinical years, significant differences in ΔE color values were observed across all groups, with the most substantial change noted in teeth immersed in cold coffee. Brackets submerged in milk demonstrated lower shear bond strength than other solutions, whereas the control group exhibited the highest shear bond strength (P = 0.01). Conclusion: The study indicates that dietary components significantly influence tooth color stability and the shear bond strength of orthodontic brackets, underscoring the importance of considering these factors in orthodontic treatment planning.展开更多
Aging is characterized by progressive degeneration of tissues and organs,and it is positively associated with an increased mortality rate.The brain,as one of the most significantly affected organs,experiences age-rela...Aging is characterized by progressive degeneration of tissues and organs,and it is positively associated with an increased mortality rate.The brain,as one of the most significantly affected organs,experiences age-related changes,including abnormal neuronal activity,dysfunctional calcium homeostasis,dysregulated mitochondrial function,and increased levels of reactive oxygen species.These changes collectively contribute to cognitive deterioration.Aging is also a key risk factor for neurodegenerative diseases,such as Alzheimer's disease and Parkinson's disease.For many years,neurodegenerative disease investigations have primarily focused on neurons,with less attention given to microglial cells.However,recently,microglial homeostasis has emerged as an important mediator in neurological disease pathogenesis.Here,we provide an overview of brain aging from the perspective of the microglia.In doing so,we present the current knowledge on the correlation between brain aging and the microglia,summarize recent progress of investigations about the microglia in normal aging,Alzheimer's disease,Parkinson's disease,Huntington's disease,and amyotrophic lateral sclerosis,and then discuss the correlation between the senescent microglia and the brain,which will culminate with a presentation of the molecular complexity involved in the microglia in brain aging with suggestions for healthy aging.展开更多
The phenomenon of an aging population is advancing at a precipitous rate.Alzheimer's disease(AD)and Parkinson's disease(PD)are two of the most common age-associated neurodegenerative diseases,both of which are...The phenomenon of an aging population is advancing at a precipitous rate.Alzheimer's disease(AD)and Parkinson's disease(PD)are two of the most common age-associated neurodegenerative diseases,both of which are primarily characterized by the accumulation of toxic proteins and the progressive demise of neuronal structures.Recent discoveries about the brain lymphatic drainage system have precipitated a growing body of investigations substantiating its novel roles,including the clearance of macromolecular waste and the trafficking of immune cells.Notably,aquaporin 4-mediated glymphatic transport,crucial for maintaining neural homeostasis,becomes disrupted during the aging process and is further compromised in the pathogenesis of AD and PD.Functional meningeal lymphatic vessels,which facilitate the drainage of cerebrospinal fluid into the deep cervical lymph nodes,are integral in bridging the central nervous system with peripheral immune responses.Dysfunction in these meningeal lymphatic vessels exacerbates pathological trajectory of the age-related neurodegenerative disease.This review explores modulatory influence of the glymphatic system and meningeal lymphatic vessels on the aging brain and its associated neurodegenerative disorders.It also encapsulates the insights of potential mechanisms and prospects of the targeted non-pharmacological interventions.展开更多
Purpose: Telomere length (TL) is an indicator of age;however, hormonal influences complicate individual aging. It remains unclear whether TL shortening is a direct factor in both individual and cellular aging. Therefo...Purpose: Telomere length (TL) is an indicator of age;however, hormonal influences complicate individual aging. It remains unclear whether TL shortening is a direct factor in both individual and cellular aging. Therefore, we examined the direct relationship between TL and cellular senescence at the cellular level. Methods: Telomerase activity, TL, and gene expression were measured in cultured human lung-, fetal-, and skin-derived fibroblasts, human skin keratinocytes, and telomerase reverse transcriptase (TERT) gene-immortalized cells using detection kits, Cawthon’s method, and reverse transcription-quantitative polymerase chain reaction, respectively. Novel substances that elongate telomeres were screened to confirm cell rejuvenation effects. Results: Long-term cell culture of TIG-1-20 normal human fibroblasts resulted in TL shortening, decreased division rate, and senescence progression, whereas in OUMS-36T-2 cells, TL elongation via TERT gene transfer increased the division rate, reduced endoplasmic reticulum stress, and upregulated genes associated with young individuals, indicating that cellular rejuvenation occurs via TL elongation. In addition, a honey child powder (HCP) extract was found through screening, and the HCP extract strongly suppressed the menin gene, resulting in increased telomerase activity and extended cell lifespan. Upon addition of the HCP extract to skin fibroblasts, gene expression of moisturizing components, including collagen, hyaluronic acid, and elastin, increased, and exhibited a rejuvenating effect with an increase in elastin amount. Conclusions: TL elongation or shortening is involved in cell proliferation rate and cellular aging, and TL elongation rejuvenates cells. In addition, HCP extract has a rejuvenating effect on cells and is expected to be a rejuvenating compound.展开更多
Here we propose a new concept of"molecule aging":with some special treatment,a molecule could be"aged"by losing some unknown tiny particles or pieces from atoms in the molecule,Such"aging"...Here we propose a new concept of"molecule aging":with some special treatment,a molecule could be"aged"by losing some unknown tiny particles or pieces from atoms in the molecule,Such"aging"or loss of unknown tiny particles does not change apparently its molecular structure or chemical composition,but some physicochemical properties could be changed irreversibly.We further confirm such"molecule aging"via a long-term electron attacking to age water(H_(2)O)molecules.The IR spectra show no structural difference between the fresh water and the aged one,while the NMR spectra show that the electron attacking can decrease the size of water clusters.Such facts indicate that the electron attacking indeed can"affect"the structure of water molecule slightly but without damaging to its basic molecule frame.Further exploration reveals that the hydrogen evolution reaction(HER)activity of the aged water molecule is lower than the fresh water on the same Pt/C electrocatalyst.The density functional theory calculations indicate that the shortened O-H bond in H_(2)O indeed can present lower HER activity,so the observed size decrease of water clusters from NMR probably could be attributed to the shortening of O-H bond in water molecules.Such results indicate significantly that the molecule aging can produce materials with new functions for new possible applications.展开更多
The aging prediction of railway catenary is of profound significance for ensuring the regular operation of electrified trains.However,in real-world scenarios,accurate predictions are challenging due to various interfe...The aging prediction of railway catenary is of profound significance for ensuring the regular operation of electrified trains.However,in real-world scenarios,accurate predictions are challenging due to various interferences.This paper addresses this challenge by proposing a novel method for predicting the aging of railway catenary based on an improved Kalman filter(KF).The proposed method focuses on modifying the priori state estimate covariance and measurement error covariance of the KF to enhance accuracy in complex environments.By comparing the optimal displacement value with the theoretically calculated value based on the thermal expansion effect of metals,it becomes possible to ascertain the aging status of the catenary.To improve prediction accuracy,a railway catenary aging prediction model is constructed by integrating the Takagi-Sugeno(T-S)fuzzy neural network(FNN)and KF.In this model,an adaptive training method is introduced,allowing the FNN to use fewer fuzzy rules.The inputs of the model include time,temperature,and historical displacement,while the output is the predicted displacement.Furthermore,the KF is enhanced by modifying its prior state estimate covariance and measurement error covariance.These modifications contribute to more accurate predictions.Lastly,a low-power experimental platform based on FPGA is implemented to verify the effectiveness of the proposed method.The test results demonstrate that the proposed method outperforms the compared method,showcasing its superior performance.展开更多
Considering the components produced by high pressure die casting(HPDC)process usually with ultra-large sizes and complex morphologies,high temperature solid solution treatment is not a suitable method to further impro...Considering the components produced by high pressure die casting(HPDC)process usually with ultra-large sizes and complex morphologies,high temperature solid solution treatment is not a suitable method to further improve their mechanical properties.In this study,two-stage aging treatment with different pre-aging times was designed and employed to further improve the mechanical properties of HPDC Al8SiMgCuZn alloy.The characteristics of precipitates were evaluated by a transmission electron microscope(TEM),and the precipitation strengthening mechanism was discussed.The results reveal that the strengthening is mainly contributed by the precipitation ofβ″phase after two-stage aging,and the number density and size of the precipitates are significantly depended on the pre-aging time.The number density of precipitates is increased with the pre-aging time prolonged from 0 h to 4 h,and then decreases with the further increase of pre-aging time from 4 h to 6 h.The precipitates with the highest density and smallest size are observed after pre-aging for 4 h.After pre-aged at 100℃for 4 h and then artificial aged at 200℃for 30 min,the yield strength of 207 MPa,ultimate tensile strength of 325 MPa and elongation of 7.6%are achieved.展开更多
文摘Aging is a natural lifelong process ending in death. Many older people are living in poverty. Older people are generally considered dependent on others as they grow older. The purpose of this article is to explore the entrepreneurship activities of Nepalese older adults. Data for this study were collected from the project Help Age International (HAI) implemented in Nepal. Qualitative data observations and interviews were used to collect data. The findings of this study show the formation of the Older People’s Association (OPA) has supported many older people to participate outside the home in various social activities. Moreover, regular deposits through OPAs offer little help. OPAs support older people in their need of financial support to implement minor entrepreneurship. Older people who received support were pleased and were actively involved in their activities and also regularly deposited money in them. Subsequently, older people’s participation in social activities has increased and also helped to lower elderly abuse, loneliness, and depression. Local governments should promote such activities which will help with healthy aging.
文摘Depression is a major health problem, especially for elderly people. According to the “homocysteine hypothesis of depression”, high homocysteine levels may cause depression of mood via cerebrovascular diseases. Whilst biologically plausible, such hypothesis needs yet confirmation. We aimed at: 1) studying the relationships between homocysteinemia (HCY) and depression in a community-dwelling cohort of people aged 70 to 75 years at baseline;2) investigating plasma levels of HCY and 3) comparing these levels between males and females, in the same population. We exploited the data from four waves (2010, 2012, 2014 and 2018) of the longitudinal study “InveCeAb”, with specific regard towards mood assessment, by Geriatric Depression Scale (GDS) scoring, and diagnosis of clinically relevant or subthreshold depression. HCY plasma levels were measured in the waves 2012, 2014 and 2018. Sample attrition was due mainly to death or overall worsening. No statistically significant differences were found in plasma homocysteine levels in each wave, according to depressive symptoms. No correlations were found between plasma HCY levels in each wave with their corresponding GDS scores, even after adjustment for folate and cobalamin blood concentrations. Dichotomized levels of HCY (≤15 vs >15 μM/l) were not associated with dichotomized GDS scores (≤4 vs higher), clinically relevant and subthreshold depression diagnosis and any antidepressive use, in any wave. First (2012) HCY levels increased with participants’ increasing age, cross-sectionally. Listwise HCY concentrations decreased along the 3 waves. HCY levels were always higher in males than in females. Our results may challenge the “homocysteine hypothesis” of depression, whilst supporting the role of high homocysteinemia as a marker of overall bad health.
基金supported by core funding provided by Temasek Life Sciences Laboratory (to CTO)。
文摘Epigenetic regulation of aging:Aging is defined as the gradual decline of physiological function and cellular integrity,causing o rganismal vulnerability to age-onset diseases and morbidity.Studies in different animal models have led to the identification of twelve aging hallmarks that shared several features:its age-associated manifestation.
基金sponsored by a grant from the National Institute of Neurological Disorders and Stroke:RO1NS116059(to MZ)。
文摘Modern neuroscience began from all reaching and fierce conflict between“neuronismo and reticulismo”——between neuronal and reticular theories of the organization of the nervous system;the conflict culminated in December of 1906 in Stockholm where Santiago Ramon y Cajal(the proponent of the neuronal doctrine)and Camillo Golgi(who advocated the syncytial reticular organization of neural networks)delivered their Noble prize lectures(Verkhratsky,2009).
基金funded by U.S.Air Force Office of Scientific Research,No.FA9550-21-1-0096FONDAP program,No.15150012+1 种基金Department of Defense grant,Nos.W81XWH2110960,ANID/FONDEF ID1ID22I10120,and ANID/NAM22I0057Swiss Consolidation Grant-The Leading House for the Latin American Region(all to CH)。
文摘As the life expectancy of the world’s population increases,age-related diseases are emerging as one of the greatest problems facing modern society.The onset of dementia and neurodegenerative diseases is strictly dependent on aging as a major risk factor and has a profound impact on various aspects of the lives of individuals and their families.
基金financially supported by grants from the National Natural Science Foundation of China (82170873,81871095)the National Natural Science Foundation of China (81974503)the Tsinghua University Spring Breeze Fund (20211080005)。
文摘Maillard reaction(MR)is a non-enzymatic browning reaction commonly seen in food processing,which occurs between reducing sugars and compounds with amino groups.Despite certain advantages based on Maillard reaction products(MRPs)found in some food for health and storage application have appeared,however,the MR occurring in human physiological environment can produce advanced glycation end products(AGEs)by non-enzymatic modification of macromolecules such as proteins,lipids and nucleic acid,which could change the structure and functional activity of the molecules themselves.In this review,we take AGEs as our main object,on the one hand,discuss physiologic aging,that is,age-dependent covalent cross-linking and modification of proteins such as collagen that occur in eyes and skin containing connective tissue.On the other hand,pathological aging associated with autoimmune and inflammatory diseases,neurodegenerative diseases,diabetes and diabetic nephropathy,cardiovascular diseases and bone degenerative diseases have been mainly proposed.Based on the series of adverse effects of accelerated aging and disease pathologies caused by MRPs,the possible harm caused by some MR can be slowed down or inhibited by artificial drug intervention,dietary pattern and lifestyle control.It also stimulates people's curiosity to continue to explore the potential link between the MR and human aging and health,which should be paid more attention to for the development of life sciences.
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funded by the Gerald Kerkut Charitable Trust (GKT)(to BR)
文摘Aging is the leading risk factor for Alzheimer’s disease and other neurodegenerative diseases. We now understand that a breakdown in the neuronal cytoskeleton, mainly underpinned by protein modifications leading to the destabilization of microtubules, is central to the pathogenesis of Alzheimer’s disease. This is accompanied by morphological defects across the somatodendritic compartment, axon, and synapse. However, knowledge of what occurs to the microtubule cytoskeleton and morphology of the neuron during physiological aging is comparatively poor. Several recent studies have suggested that there is an age-related increase in the phosphorylation of the key microtubule stabilizing protein tau, a modification, which is known to destabilize the cytoskeleton in Alzheimer’s disease. This indicates that the cytoskeleton and potentially other neuronal structures reliant on the cytoskeleton become functionally compromised during normal physiological aging. The current literature shows age-related reductions in synaptic spine density and shifts in synaptic spine conformation which might explain age-related synaptic functional deficits. However, knowledge of what occurs to the microtubular and actin cytoskeleton, with increasing age is extremely limited. When considering the somatodendritic compartment, a regression in dendrites and loss of dendritic length and volume is reported whilst a reduction in soma volume/size is often seen. However, research into cytoskeletal change is limited to a handful of studies demonstrating reductions in and mislocalizations of microtubule-associated proteins with just one study directly exploring the integrity of the microtubules. In the axon, an increase in axonal diameter and age-related appearance of swellings is reported but like the dendrites, just one study investigates the microtubules directly with others reporting loss or mislocalization of microtubule-associated proteins. Though these are the general trends reported, there are clear disparities between model organisms and brain regions that are worthy of further investigation. Additionally, longitudinal studies of neuronal/cytoskeletal aging should also investigate whether these age-related changes contribute not just to vulnerability to disease but also to the decline in nervous system function and behavioral output that all organisms experience. This will highlight the utility, if any, of cytoskeletal fortification for the promotion of healthy neuronal aging and potential protection against age-related neurodegenerative disease. This review seeks to summarize what is currently known about the physiological aging of the neuron and microtubular cytoskeleton in the hope of uncovering mechanisms underpinning age-related risk to disease.
基金supported by the National Key Research and Development Program of China(2022YFD1300202)the Technology Innovation and Application Development Special Project of Chongqing(cstc2021jscx-gksb X0008)+2 种基金the National Natural Science Foundation of China(32102623)the National Natural Science Foundation of Chongqing(cstc2021jcyj-msxm X0875)the Ph D Train Scientific Research Project of Chongqing(CSTB2022BSXM-JCX0002)。
文摘Background The ovaries are one of the first organs that undergo degenerative changes earlier in the aging process,and ovarian aging is shown by a decrease in the number and quality of oocytes.However,little is known about the molecular mechanisms of female age-related fertility decline in different types of ovarian cells during aging,especially in goats.Therefore,the aim of this study was to reveal the mechanisms driving ovarian aging in goats at single-cell resolution.Results For the first time,we surveyed the single-cell transcriptomic landscape of over 27,000 ovarian cells from newborn,young and aging goats,and identified nine ovarian cell types with distinct gene-expression signatures.Functional enrichment analysis showed that ovarian cell types were involved in their own unique biological processes,such as Wnt beta-catenin signalling was enriched in germ cells,whereas ovarian steroidogenesis was enriched in granulosa cells(GCs).Further analysis showed that ovarian aging was linked to GCs-specific changes in the antioxidant system,oxidative phosphorylation,and apoptosis.Subsequently,we identified a series of dynamic genes,such as AMH,CRABP2,THBS1 and TIMP1,which determined the fate of GCs.Additionally,FOXO1,SOX4,and HIF1A were identified as significant regulons that instructed the differentiation of GCs in a distinct manner during ovarian aging.Conclusions This study revealed a comprehensive aging-associated transcriptomic atlas characterizing the cell typespecific mechanisms during ovarian aging at the single-cell level and offers new diagnostic biomarkers and potential therapeutic targets for age-related goat ovarian diseases.
文摘Autophagy is a prosurvival mechanism for the clearance of accumulated abnormal proteins,damaged organelles,and excessive lipids within mammalian cells.A growing body of data indicates that autophagy is reduced in aging cells.This reduction leads to various diseases,such as myocardial hypertrophy,infarction,and atherosclerosis.Recent studies in animal models of an aging heart showed that fasting-induced autophagy improved cardiac function and longevity.This improvement is related to autophagic clearance of damaged cellular components via either bulk or selective autophagy(such as mitophagy).In this editorial,we summarize the mechanisms of autophagy in normal and aging hearts.In addition,the protective effect of fasting-induced autophagy in cardiac aging has been highlighted.
基金the National Key R&D Program of China(2023YFB3812901)the Postdoctoral Fellowship Program of CPSF(No.GZC20230239)+1 种基金the China Postdoctoral Science Foundation(No.2023M740219)the National Natural Science Foundation of China(No.22209094)。
文摘To study the atmospheric aging of acrylic coatings,a two-year aging exposure experiment was conducted in 13 representative climatic environments in China.An atmospheric aging evaluation model of acrylic coatings was developed based on aging data including11 environmental factors from 567 cities.A hybrid method of random forest and Spearman correlation analysis was used to reduce the redundancy and multicollinearity of the data set by dimensionality reduction.A semi-supervised collaborative trained regression model was developed with the environmental factors as input and the low-frequency impedance modulus values of the electrochemical impedance spectra of acrylic coatings in 3.5wt%NaCl solution as output.The model improves accuracy compared to supervised learning algorithms model(support vector machines model).The model provides a new method for the rapid evaluation of the aging performance of acrylic coatings,and may also serve as a reference to evaluate the aging performance of other organic coatings.
文摘Introduction: The stability of orthodontic brackets throughout orthodontic treatment plays a critical role in the treatment’s effectiveness. The present in vitro study was designed to assess the impact of various dietary components on the performance of orthodontic brackets. Methods: Metal orthodontic brackets were bonded to 66 extracted anterior teeth divided into groups based on the solution type: Milk, Gatorade, Cold Coffee, and a control group using water. Each group consisted of 20 teeth except for the control group, which included six teeth. The bracketed teeth were submerged in their respective solutions for 15 minutes three times daily at different intervals to mimic an in vivo environment and were stored in artificial saliva at room temperature (23?C). The specimens underwent artificial aging through 10,000 cycles of thermocycling (representing one clinical year) between 5?C and 55?C. Shade measurements were taken using a VITA Easy Shade device, capturing the classic shade and L*, a*, and b* values. Delta E values were calculated immediately post-bonding and after 7 days, 1 month, 1, and 2 clinical years. The shear bond strength of each bracket was measured using an ultra-tester machine. Results: After two clinical years, significant differences in ΔE color values were observed across all groups, with the most substantial change noted in teeth immersed in cold coffee. Brackets submerged in milk demonstrated lower shear bond strength than other solutions, whereas the control group exhibited the highest shear bond strength (P = 0.01). Conclusion: The study indicates that dietary components significantly influence tooth color stability and the shear bond strength of orthodontic brackets, underscoring the importance of considering these factors in orthodontic treatment planning.
基金supported by the Operating Grant to Chongqing Key Laboratory of Neurodegenerative Diseases(Grant No.1000013)the Plan for High-level Talent Introduction(Grant No.2000055).
文摘Aging is characterized by progressive degeneration of tissues and organs,and it is positively associated with an increased mortality rate.The brain,as one of the most significantly affected organs,experiences age-related changes,including abnormal neuronal activity,dysfunctional calcium homeostasis,dysregulated mitochondrial function,and increased levels of reactive oxygen species.These changes collectively contribute to cognitive deterioration.Aging is also a key risk factor for neurodegenerative diseases,such as Alzheimer's disease and Parkinson's disease.For many years,neurodegenerative disease investigations have primarily focused on neurons,with less attention given to microglial cells.However,recently,microglial homeostasis has emerged as an important mediator in neurological disease pathogenesis.Here,we provide an overview of brain aging from the perspective of the microglia.In doing so,we present the current knowledge on the correlation between brain aging and the microglia,summarize recent progress of investigations about the microglia in normal aging,Alzheimer's disease,Parkinson's disease,Huntington's disease,and amyotrophic lateral sclerosis,and then discuss the correlation between the senescent microglia and the brain,which will culminate with a presentation of the molecular complexity involved in the microglia in brain aging with suggestions for healthy aging.
基金supported by the National Natural Science Foundation of China(Grant Nos.82071199 and 81871117)the Natural Science Foundation of Jiangsu Province(Grant No.BK20230057)Shandong Postdoctoral Innovative Talents Program(Grant No.SDBX2023056).
文摘The phenomenon of an aging population is advancing at a precipitous rate.Alzheimer's disease(AD)and Parkinson's disease(PD)are two of the most common age-associated neurodegenerative diseases,both of which are primarily characterized by the accumulation of toxic proteins and the progressive demise of neuronal structures.Recent discoveries about the brain lymphatic drainage system have precipitated a growing body of investigations substantiating its novel roles,including the clearance of macromolecular waste and the trafficking of immune cells.Notably,aquaporin 4-mediated glymphatic transport,crucial for maintaining neural homeostasis,becomes disrupted during the aging process and is further compromised in the pathogenesis of AD and PD.Functional meningeal lymphatic vessels,which facilitate the drainage of cerebrospinal fluid into the deep cervical lymph nodes,are integral in bridging the central nervous system with peripheral immune responses.Dysfunction in these meningeal lymphatic vessels exacerbates pathological trajectory of the age-related neurodegenerative disease.This review explores modulatory influence of the glymphatic system and meningeal lymphatic vessels on the aging brain and its associated neurodegenerative disorders.It also encapsulates the insights of potential mechanisms and prospects of the targeted non-pharmacological interventions.
文摘Purpose: Telomere length (TL) is an indicator of age;however, hormonal influences complicate individual aging. It remains unclear whether TL shortening is a direct factor in both individual and cellular aging. Therefore, we examined the direct relationship between TL and cellular senescence at the cellular level. Methods: Telomerase activity, TL, and gene expression were measured in cultured human lung-, fetal-, and skin-derived fibroblasts, human skin keratinocytes, and telomerase reverse transcriptase (TERT) gene-immortalized cells using detection kits, Cawthon’s method, and reverse transcription-quantitative polymerase chain reaction, respectively. Novel substances that elongate telomeres were screened to confirm cell rejuvenation effects. Results: Long-term cell culture of TIG-1-20 normal human fibroblasts resulted in TL shortening, decreased division rate, and senescence progression, whereas in OUMS-36T-2 cells, TL elongation via TERT gene transfer increased the division rate, reduced endoplasmic reticulum stress, and upregulated genes associated with young individuals, indicating that cellular rejuvenation occurs via TL elongation. In addition, a honey child powder (HCP) extract was found through screening, and the HCP extract strongly suppressed the menin gene, resulting in increased telomerase activity and extended cell lifespan. Upon addition of the HCP extract to skin fibroblasts, gene expression of moisturizing components, including collagen, hyaluronic acid, and elastin, increased, and exhibited a rejuvenating effect with an increase in elastin amount. Conclusions: TL elongation or shortening is involved in cell proliferation rate and cellular aging, and TL elongation rejuvenates cells. In addition, HCP extract has a rejuvenating effect on cells and is expected to be a rejuvenating compound.
基金funded by the Key Research and Development Program sponsored by the Ministry of Science and Technology(MOST)(2022YFA1203400)National Natural Science Foundation of China(21925205,22072145,21372155,22005294,and 22102172)。
文摘Here we propose a new concept of"molecule aging":with some special treatment,a molecule could be"aged"by losing some unknown tiny particles or pieces from atoms in the molecule,Such"aging"or loss of unknown tiny particles does not change apparently its molecular structure or chemical composition,but some physicochemical properties could be changed irreversibly.We further confirm such"molecule aging"via a long-term electron attacking to age water(H_(2)O)molecules.The IR spectra show no structural difference between the fresh water and the aged one,while the NMR spectra show that the electron attacking can decrease the size of water clusters.Such facts indicate that the electron attacking indeed can"affect"the structure of water molecule slightly but without damaging to its basic molecule frame.Further exploration reveals that the hydrogen evolution reaction(HER)activity of the aged water molecule is lower than the fresh water on the same Pt/C electrocatalyst.The density functional theory calculations indicate that the shortened O-H bond in H_(2)O indeed can present lower HER activity,so the observed size decrease of water clusters from NMR probably could be attributed to the shortening of O-H bond in water molecules.Such results indicate significantly that the molecule aging can produce materials with new functions for new possible applications.
基金supported by the Science and Technology Research Project of Henan Province (No.222102210087)the Science and Technology Research Project of Henan Province (No.222102220102).
文摘The aging prediction of railway catenary is of profound significance for ensuring the regular operation of electrified trains.However,in real-world scenarios,accurate predictions are challenging due to various interferences.This paper addresses this challenge by proposing a novel method for predicting the aging of railway catenary based on an improved Kalman filter(KF).The proposed method focuses on modifying the priori state estimate covariance and measurement error covariance of the KF to enhance accuracy in complex environments.By comparing the optimal displacement value with the theoretically calculated value based on the thermal expansion effect of metals,it becomes possible to ascertain the aging status of the catenary.To improve prediction accuracy,a railway catenary aging prediction model is constructed by integrating the Takagi-Sugeno(T-S)fuzzy neural network(FNN)and KF.In this model,an adaptive training method is introduced,allowing the FNN to use fewer fuzzy rules.The inputs of the model include time,temperature,and historical displacement,while the output is the predicted displacement.Furthermore,the KF is enhanced by modifying its prior state estimate covariance and measurement error covariance.These modifications contribute to more accurate predictions.Lastly,a low-power experimental platform based on FPGA is implemented to verify the effectiveness of the proposed method.The test results demonstrate that the proposed method outperforms the compared method,showcasing its superior performance.
基金financially supported by the Natural Science Foundation of Guangdong Province(Nos.2021A151510042,2021A1515011728)the China Postdoctoral Science Foundation(2022M711190)+1 种基金the National Natural Science Foundation of China(No.51875211)the Key Area Research and Development Program of Guangdong Province(No.2020B010186002)。
文摘Considering the components produced by high pressure die casting(HPDC)process usually with ultra-large sizes and complex morphologies,high temperature solid solution treatment is not a suitable method to further improve their mechanical properties.In this study,two-stage aging treatment with different pre-aging times was designed and employed to further improve the mechanical properties of HPDC Al8SiMgCuZn alloy.The characteristics of precipitates were evaluated by a transmission electron microscope(TEM),and the precipitation strengthening mechanism was discussed.The results reveal that the strengthening is mainly contributed by the precipitation ofβ″phase after two-stage aging,and the number density and size of the precipitates are significantly depended on the pre-aging time.The number density of precipitates is increased with the pre-aging time prolonged from 0 h to 4 h,and then decreases with the further increase of pre-aging time from 4 h to 6 h.The precipitates with the highest density and smallest size are observed after pre-aging for 4 h.After pre-aged at 100℃for 4 h and then artificial aged at 200℃for 30 min,the yield strength of 207 MPa,ultimate tensile strength of 325 MPa and elongation of 7.6%are achieved.