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 complex morphological,anatomical,physiological,and chemical mechanisms within the aging brain have been the hot topic of research for centuries.The aging process alters the brain structure that affects functions a...The complex morphological,anatomical,physiological,and chemical mechanisms within the aging brain have been the hot topic of research for centuries.The aging process alters the brain structure that affects functions and cognitions,but the worsening of such processes contributes to the pathogenesis of neurodegenerative disorders,such as Alzheimer's disease.Beyond these observable,mild morphological shifts,significant functional modifications in neurotransmission and neuronal activity critically influence the aging brain.Understanding these changes is important for maintaining cognitive health,especially given the increasing prevalence of age-related conditions that affect cognition.This review aims to explore the age-induced changes in brain plasticity and molecular processes,differentiating normal aging from the pathogenesis of Alzheimer's disease,thereby providing insights into predicting the risk of dementia,particularly Alzheimer's disease.展开更多
As people live longer,the burden of aging-related brain diseases,especially dementia,is increasing.Brain aging increases the risk of cognitive impairment,which manifests as a progressive loss of neuron function caused...As people live longer,the burden of aging-related brain diseases,especially dementia,is increasing.Brain aging increases the risk of cognitive impairment,which manifests as a progressive loss of neuron function caused by the impairment of synaptic plasticity via disrupting lipid homeostasis.Therefore,supplemental dietary lipids have the potential to prevent brain aging.This review summarizes the important roles of dietary lipids in brain function from both structure and mechanism perspectives.Epidemiological and animal studies have provided evidence of the functions of polyunsaturated fatty acids(PUFAs)in brain health.The results of interventions indicate that phospholipids—including phosphatidylcholine,phosphatidylserine,and plasmalogen—are efficient in alleviating cognitive impairment during aging,with plasmalogen exhibiting higher efficacy than phosphatidylserine.Plasmalogen is a recognized nutrient used in clinical trials due to its special vinyl ether bonds and abundance in the postsynaptic membrane of neurons.Future research should determine the dose-dependent effects of plasmalogen in alleviating brain-aging diseases and should develop extraction and storage procedures for its clinical application.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
Oxidative stress is currently considered to be the main cause of brain aging.Astaxanthin can improve oxidative stress under multiple pathological conditions.It is therefore hypothesized that astaxanthin might have the...Oxidative stress is currently considered to be the main cause of brain aging.Astaxanthin can improve oxidative stress under multiple pathological conditions.It is therefore hypothesized that astaxanthin might have therapeutic effects on brain aging.To validate this hypothesis and investigate the underlying mechanisms,a mouse model of brain aging was established by injecting amyloid beta(Aβ)25-35(5μM,3μL/injection,six injections given every other day)into the right lateral ventricle.After 3 days of Aβ25-35 injections,the mouse models were intragastrically administered astaxanthin(0.1 mL/d,10 mg/kg)for 30 successive days.Astaxanthin greatly reduced the latency to find the platform in the Morris water maze,increased the number of crossings of the target platform,and increased the expression of brain-derived neurotrophic factor,synaptophysin,sirtuin 1,and peroxisome proliferator-activated receptor-γ coactivator 1α.Intraperitoneal injection of the sirtuin 1 inhibitor nicotinamide(500μM/d)for 7 successive days after astaxanthin intervention inhibited these phenomena.These findings suggest that astaxanthin can regulate the expression of synaptic proteins in mouse hippocampus through the sirtuin 1/peroxisome proliferator-activated receptor-γcoactivator 1αsignaling pathway,which leads to improvements in the learning,cognitive,and memory abilities of mice.The study was approved by the Animal Ethics Committee,China Medical University,China(approval No.CMU2019294)on January 15,2019.展开更多
Aging is well known to be the main risk factor for the neurodegenerative pathologies,in particular,Parkinson’s disease（PD）and Alzheimer’s disease（AD）.In aging and in the diseases,similar changes in various hallm...Aging is well known to be the main risk factor for the neurodegenerative pathologies,in particular,Parkinson’s disease（PD）and Alzheimer’s disease（AD）.In aging and in the diseases,similar changes in various hallmarks of neurodegeneration（lipofuscin accumulation,autophagia weakening,and disturbances in functions of mitochondriaand lysosomes） were shown （Tan et al., 2014）. Furthermore, dopami- nergic system （DAS） involvement in mechanisms of aging, PD, and AD were revealed （Martorana and Koch, 2014）.展开更多
Characterizing the trajectory of the healthy aging brain and exploring age-related structural changes in the brain can help deepen our understanding of the mechanism of brain aging.Currently,most structural magnetic r...Characterizing the trajectory of the healthy aging brain and exploring age-related structural changes in the brain can help deepen our understanding of the mechanism of brain aging.Currently,most structural magnetic resonance imaging literature explores brain aging merely from the perspective of morphological features,which cannot fully utilize the grayscale values containing important intrinsic information about brain structure.In this study,we propose the construction of two-dimensional horizontal visibility graphs based on the pixel intensity values of the gray matter slices directly.Normalized network structure entropy(NNSE)is then introduced to quantify the overall heterogeneities of these graphs.The results demonstrate a decrease in the NNSEs of gray matter with age.Compared with the middle-aged and the elderly,the larger values of the NNSE in the younger group may indicate more homogeneous network structures,smaller differences in importance between nodes and thus a more powerful ability to tolerate intrusion.In addition,the hub nodes of different adult age groups are primarily located in the precuneus,cingulate gyrus,superior temporal gyrus,inferior temporal gyrus,parahippocampal gyrus,insula,precentral gyrus and postcentral gyrus.Our study can provide a new perspective for understanding and exploring the structural mechanism of brain aging.展开更多
Brain aging is the main manifestation of nervous system senescence, and is clinically represented by reduced learning and memory capacities and slowed reactions. Several studies have shown that Chinese medicines can e...Brain aging is the main manifestation of nervous system senescence, and is clinically represented by reduced learning and memory capacities and slowed reactions. Several studies have shown that Chinese medicines can effectively slow these processes. For example, polysaccharides from Schisandra chinensis have anti-aging effects, while Buyang Huanwu decoction can effectively improve cerebral blood flow and hemorheology,展开更多
Brain aging is a recognized risk factor for neurodegenerative diseases like Alzheimer’s disease,Parkinson’s disease,and amyotrophic lateral sclerosis(ALS,Lou Gehrig’s disease),but the intricate interplay between br...Brain aging is a recognized risk factor for neurodegenerative diseases like Alzheimer’s disease,Parkinson’s disease,and amyotrophic lateral sclerosis(ALS,Lou Gehrig’s disease),but the intricate interplay between brain aging and the pathogenesis of these conditions remains inadequately understood.Cellular senescence is considered to contribute to cellular dysfunction and inflammaging.According to the threshold theory of senescent cell accumulation,the vulnerability to neurodegenerative diseases is associated with the rates of senescent cell generation and clearance within the brain.Given the role of microglia in eliminating senescent cells,the accumulation of senescent microglia may lead to the acceleration of brain aging,contributing to inflammaging and increased vulnerability to neurodegenerative diseases.In this review,we propose the idea that the senescence of microglia,which is notably vulnerable to aging,could potentially serve as a central catalyst in the progression of neurodegenerative diseases.The senescent microglia are emerging as a promising target for mitigating neurodegenerative diseases.展开更多
Age-related cognitive decline and dementia are significant manifestations of brain aging.As the elderly population grows rapidly,the health and socio-economic impacts of cognitive dysfunction have become increasingly ...Age-related cognitive decline and dementia are significant manifestations of brain aging.As the elderly population grows rapidly,the health and socio-economic impacts of cognitive dysfunction have become increasingly significant.Although clinical treatment of dementia has faced considerable challenges over the past few decades,with limited breakthroughs in slowing its progression,there has been substantial progress in understanding the molecular mechanisms and hallmarks of age-related dementia(ARD).This progress brings new hope for the intervention and treatment of this disease.In this review,we categorize the latest findings in ARD biomarkers into four stages based on disease progression:Healthy brain,preclinical,mild cognitive impairment,and dementia.We then systematically summarize the most promising therapeutic approaches to prevent or slow ARD at four levels:Genome and epigenome,organelle,cell,and organ and organism.We emphasize the importance of early prevention and detection,along with the implementation of combined treatments as multimodal intervention strategies,to address brain aging and ARD in the future.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
BACKGROUND： The most prominent characteristic of brain aging is decreased learning and memory ability. The functions of learning and memory are closely related to intracerebral acetylcholinesterase （ACHE） and monoa...BACKGROUND： The most prominent characteristic of brain aging is decreased learning and memory ability. The functions of learning and memory are closely related to intracerebral acetylcholinesterase （ACHE） and monoamine neurotransmitter activity. Previous studies have shown that Schisandra chinensis polysaccharide has an anti-aging effect. OBJECTIVE： To explore the effects of Schisandra chinensis polysaccharide on AChE activity and monoamine neurotransmitter content, as well as learning and memory ability in a D-galactose-induced aging mouse brain model compared with the positive control drug Kangnaoling. DESIGN, TIME AND SETTING： Completely randomized, controlled experiment based on neurobiochemistry was performed at the Pharmacological Laboratory, Henan University of Traditional Chinese Medicine from September to December 2003. MATERIALS： Schisandra chinensis was purchased from Henan Provincial Medicinal Company. Schisandra chinensis polysaccharide was obtained by water extraction and alcohol precipitation. Kangnaoling pellets were provided by Liaoning Tianlong Pharmaceutical （batch No. 20030804; state drug permit No. H21023095）. A total of 50 six-week-old Kunming mice were randomly divided into five groups： blank control, model, Kangnaoling, high and low dosage Schisandra chinensis polysaccharide groups, with 10 mice per group. METHODS： Mice in the blank control group were subcutaneously injected with 0.5 mL/20 g normal saline into the nape of the neck each day, while the remaining mice were subcutaneously injected with 5% D-galactose saline solution （0.5 mL/20 g） in the nape for 40 days to induce a brain aging model. On day 11, mice in the high and low dosage Schisandra chinensis polysaccharide groups were intragastrically infused with 20 mg/mL and 10 mg/mL Schisandra chinensis polysaccharide solution （0.2 mL/10 g）, respectively. Mice from the Kangnaoling group were intragastrically infused with 35 mg/mL Kangnaoling suspension （0.2 mL/10 g）, and the mice in the model group were intragastrically infused with the same volume of normal saline （0.2 mL/10 g） once per day for 30 consecutive days. MAIN OUTCOME MEASURES： Two hours after the final administration, pathohistological changes in the cerebral cortex and hippocampus were observed using hematoxylin ＆ eosin staining. AChE activity was detected using chromatometry. Monoamine neurotransmitter content was measured using fluorimetry. Learning and memory was measured using the step down test and darkness avoidance test. RESULTS： Both Schisandra chinensis polysaccharide and Kangnaoling improved pathological injury to the cerebral cortex and hippocampus in a mouse model of brain aging. Compared with the blank control group, AChE activity and content of norepinephrine （NA）, dopamine （DA）, and 5-hydroxytryptamine （5-HT） were significantly decreased in the model group （P 〈 0.01 ）. In contrast, AChE activity and NA, DA, and 5-HT levels significantly increased in the Kangnaoling and high dosage Schisandra chinensis polysaccharide groups （P 〈 0.01）, while NA levels significantly increased in the low dosage Schisandra chinensis polysaccharide group （P 〈 0.01）. Drug treatment improved learning and memory abilities （P 〈 0.01 or P 〈 0.05）. CONCLUSION： Schisandra chinensis polysaccharide significantly increased levels of central neurotransmitters and improved learning and memory in a mouse model of brain aging. The effects of Schisandra chinensis polysaccharide were equal to that of Kangnaoling pellets.展开更多
The regulation of gene expression in brain vicissitudes during aging is still not much known and explored. Differential gene expression and regulation is a key factor involved to identify the important landmarks withi...The regulation of gene expression in brain vicissitudes during aging is still not much known and explored. Differential gene expression and regulation is a key factor involved to identify the important landmarks within the brain transcriptome to study neuronal aging. Recently</span><span style="font-family:Verdana;">,</span><span style="font-family:Verdana;"> transcriptomic studies are highly explored to understand and depict diseased versus normal as next generation sequencing enable</span><span style="font-family:Verdana;">s</span><span style="font-family:Verdana;"> to capture the complete biological context to the entire genome. Study of gene expression during aging compared to young flies provides a signature and scenario of gene expression and regulation during aging. In this study</span><span style="font-family:Verdana;">,</span><span style="font-family:""><span style="font-family:Verdana;"> we took advantage of NGS raw data of young and old flies head from SRA database of NCBI and decrypted the gene expression regulation during normal aging in drosophila model. We identified 350 genes with significant differential expression between young and old flies having 0.01% FDR. Various pathways in context to identified genes which are involved in aging include autophagy </span><i><span style="font-family:Verdana;">i.e.</span></i><span style="font-family:Verdana;"> cell death and apoptosis, proteolysis</span><span style="font-family:Verdana;">, oxidative</span><span style="font-family:Verdana;"> stress, declination grey and white matter and neurotransmitter levels, mitochondrial discrepancy, electron transport chain, sugar degradation pathways, activation of transcription factors involved in epigenetic changes, regulators involved in negative and positive regulation WNT signaling pathways, G protein coupled receptor etc. as all these factors contribute to neurodegeneration and possibly dementia in normal aging. So, to find the specific genes and regulators which are differentially expressed in normal aging</span></span><span style="font-family:Verdana;">,</span><span style="font-family:Verdana;"> we investigate brain transcriptome of normal aging flies compared to young flies which offer a repertoire of genes, regulators and factors involved in network of neurodegeneration to establish direct correlation between aging and dementia. We also identified the pathways which are involved in aging and corresponding gene regulation in these pathways in aging flies brain. It is found that there are some common pathways whose genes and regulators are highly differentially regulated in both aging and dementia.展开更多
Brain development and aging are associated with alterations in multiple epigenetic systems, including DNA methylation and demethylation patterns. Here, we observed that the levels of the 5- hydroxymethylcytosine （5hm...Brain development and aging are associated with alterations in multiple epigenetic systems, including DNA methylation and demethylation patterns. Here, we observed that the levels of the 5- hydroxymethylcytosine （5hmC） ten-eleven transtocation （TET） enzyme-mediated active DNA demethylation products were dynamically changed and involved in postnatal brain development and aging in tree shrews （Tupaia belangeri chinensis）. The levels of 5hmC in multiple anatomic structures showed a gradual increase throughout postnatal development, whereas a significant decrease in 5hmC was found in several brain regions in aged tree shrews, including in the prefrontal cortex and hippocampus, but not the cerebellum. Active changes in Tet mRNA levels indicated that TET2 and TET3 predominantly contributed to the changes in 5hmC levels. Our findings provide new insight into the dynamic changes in 5hmC levels in tree shrew brains during postnatal development and aging processes.展开更多
The aging process in mammals is correlated with changes in psychomotor performance, cognitive function, and ability to adapt to stress (Montgomery et al., 1982; Lorens et al., 1990). These changes may be related to al...The aging process in mammals is correlated with changes in psychomotor performance, cognitive function, and ability to adapt to stress (Montgomery et al., 1982; Lorens et al., 1990). These changes may be related to alterations in neuronal tissue that occur during the aging process. The normal aging process may be conceived of as the neuronal cell’s increasing inability to maintain normal cellular function which ultimately results in a number of morphological and biochemical changes. Morphologically, there is a loss of neuronal cells with increasing age (Brizzee and展开更多
Rats of both sexes were fed on a basal feed containing 1% refined konjac meal (RKM) for 18 months and the effects of RKM on the cell aging were observed. A comparable group fed on the basic feed was used as the contro...Rats of both sexes were fed on a basal feed containing 1% refined konjac meal (RKM) for 18 months and the effects of RKM on the cell aging were observed. A comparable group fed on the basic feed was used as the control. Results obtained demonstrate that the long-term feeding of RKM to rats can delay the course of cell aging of the gliocyte, cadiomyocyte, and the endothelial cell of the large and medium arteriases, hence it is likely to delay the occurrence of arteriosclerosis and improve the functions of the brain, heart and vascular system.展开更多
D-galactose has been widely used in aging research because of its efficacy in inducing senescence and accelerating aging in animal models. The present study investigated the benefits of exercise for preventing neurode...D-galactose has been widely used in aging research because of its efficacy in inducing senescence and accelerating aging in animal models. The present study investigated the benefits of exercise for preventing neurodegeneration, such as synaptic plasticity, spatial learning and memory abilities, in mouse models of aging. D-galactose-induced aging mice were administered daily subcutaneous injections of D-galactose at the base of the neck for 10 consecutive weeks. Then, the mice were subjected to exercise training by running on a treadmill for 6 days a week. Shortened escape latency in a Morris water maze test indicated that exercise improved learning and memory in aging mice. The ameliorative changes were likely induced by an upregulation of Bcl-2 and brain-derived neurotrophic factor, the repression of apoptosis factors such as Fas and Bax, and an increase in the activity of glucose transporters-1 and 4. The data suggest moderate exercise may retard or inhibit neurodegeneration in D-galactose-induced aging mice.展开更多
<strong>Objective</strong>: Purpose of this study was to investigate the behavioral and brain activity impairments in patients after moderate traumatic brain injury (mTBI) in comparison with the normal ran...<strong>Objective</strong>: Purpose of this study was to investigate the behavioral and brain activity impairments in patients after moderate traumatic brain injury (mTBI) in comparison with the normal ranges while dual-tasks performing. We would like to evaluate dual-tasking as diagnostic and rehabilitation tool and to test hypothesis of brain aging after mTBI. <strong>Material and Methods</strong>: Electroencephalographic (EEG), stabilographic and clinical study was performed in 11 patients (mean age 28.8 ± 8.4 years) for up to 1 - 12 months after a mTBI in comparison with 17 healthy subjects (26.7 ± 5.1 years). All the participants performed two motor and two cognitive tasks presented separately, and simultaneously (dual-tasking). <strong>Results</strong>: Clinical examination revealed predominantly cognitive deficit in mTBI patients with intact postural control. EEG data demonstrated coherence decrease for slow (delta-theta) rhythms in frontal-temporal areas predominantly for left hemisphere during cognitive tasks performance. In contrast, EEG coherence for slow spectral bands increased in the same areas in healthy volunteers. EEG coherence increased for fast spectral bands—alpha2 and beta, predominantly in right hemisphere while both healthy adults and patients performed motor components of dual tasks. Rehabilitation course with dual tasks, led to a predominant reduction in cognitive deficits, and EEG coherence increases at the frontal-temporal areas of the left hemisphere. <strong>Conclusions</strong>: Dual-tasks may be used as diagnostic tool in patients after mTBI. This approach demonstrates predominant cognitive deficit, and left hemispheric dysfunction in patients similar to elderly persons and support the hypothesis of brain aging after TBI. Pilot studies also suggested rehabilitation effect of dual-tasking in mTBI patients.展开更多
BACKGROUND： Prophylactic dietary restriction （DR）, whether lifelong or started in adulthood,retards the aging process and attenuates cognitive decline in rodents. However, whether the anti-aging and neuroprotective...BACKGROUND： Prophylactic dietary restriction （DR）, whether lifelong or started in adulthood,retards the aging process and attenuates cognitive decline in rodents. However, whether the anti-aging and neuroprotective efficacy of DR initiate late in life or accompany the aging process remains unclear.OBJECTIVE： The present study sought to： （1） determine if DR could protect against behavioral decline in mice when implemented during the aging process induced by D-galactose and （2） examine neuronal apoptosis in these aged brains and whether DR could block apoptosis.DESIGN, TIME AND SETTING： The randomized controlled animal study. The experiment was performed at the Experimental Animal Center of Capital Medical University and the Laboratory Center of School of Public Health of Captial Medical University of China from April 2006 to October 2007.MATERIALS： D-galactose （D-gal） was purchased from Beijing Chemical-Regent Company （Beijing, China）. Terminal transferase dUTP nick end labeling （TUNEL） detection kit was obtained from Roche, Germany. Assay kits for antioxidant enzyme activities and malondialdehyde contents were purchased from Jiancheng Institute of Biotechnology （Nanjing, China）. Morris water maze （Friends Honesty Life Sciences Co. Ltd., Hong Kong, China） and Flow Cytometry （Coulter, USA） were used in this study.METHODS： A total of 40 male Institute of Cancer Research （lCR） mice, 3 months old, were equally and randomly divided into D-gal treatment, DR treatment, D-gal ＋ DR treatment and normal control groups, and were then randomly assigned to one of two feeding regimens： ad libitum access to food or DR which received a 70% amount of daily food intake as that by ad libitum fed mice. There were two replicates per feeding regimen and mice were fed for 10 weeks,with or without a daily subcutaneous injection of D-gal at 100 mg/kg.MAIN OUTCOME MEASURES： Animals＇ spatial learning and memory performance were tested in the Morris water maze. Neuronal apoptosis rates were evaluated by Annexin V/flow cytometry assay and TUNEL assay. Lipid peroxidation levels and antioxidant defense capacity of the brain were measured using testing kits.RESULTS： DR markedly reduced the prolonged escape latency of D-gal mice in the water maze test （P〈0.01）. Annexin V and TUNEL assays showed that the D-gal mice had a significant higher percentage of neuronal apoptosis compared with normal control mice （P〈0.05）, and that DR treatment markedly decreased this apoptotic cell death （P〈0.05）. DR also reversed the decline of total superoxide dismutase and glutathione peroxidase activities and the increase of malondialdehyde levels in the brain of D-gal mice （P〈0.05, respectively）.CONCLUSION： DR reduces the impact of D-gal-induced brain aging in mice and can reverse performance decline and neurobiochemical impairments. These results demonstrate that implementation of DR in conditions of chronic oxidative stress can be neuroprotective, and that senium DR can be beneficial for healthy aging.展开更多
One of the basic questions in the aging field is whether there is a fundamental difference between the aging of lower invertebrates and mammals.A major difference between the lower invertebrates and mammals is the abu...One of the basic questions in the aging field is whether there is a fundamental difference between the aging of lower invertebrates and mammals.A major difference between the lower invertebrates and mammals is the abundancy of noncoding RNAs,most of which are not conserved.We have previously identified a noncoding RNA Terc-53 that is derived from the RNA component of telomerase Terc.To study its physiological functions,we generated two transgenic mouse models overexpressing the RNA in wild-type and early-aging Terc^(−/−)backgrounds.Terc-53 mice showed age-related cognition decline and shortened life span,even though no developmental defects or physiological abnormality at an early age was observed,indicating its involvement in normal aging of mammals.Subsequent mechanistic study identified hyaluronan-mediated motility receptor(Hmmr)as the main effector of Terc-53.Terc-53 mediates the degradation of Hmmr,leading to an increase of inflammation in the affected tissues,accelerating organismal aging.adeno-associated virus delivered supplementation of Hmmr in the hippocampus reversed the cognition decline in Terc-53 transgenic mice.Neither Terc-53 nor Hmmr has homologs in C.elegans.Neither do arthropods express hyaluronan.These findings demonstrate the complexity of aging in mammals and open new paths for exploring noncoding RNA and Hmmr as means of treating age-related physical debilities and improving healthspan.展开更多
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.
文摘The complex morphological,anatomical,physiological,and chemical mechanisms within the aging brain have been the hot topic of research for centuries.The aging process alters the brain structure that affects functions and cognitions,but the worsening of such processes contributes to the pathogenesis of neurodegenerative disorders,such as Alzheimer's disease.Beyond these observable,mild morphological shifts,significant functional modifications in neurotransmission and neuronal activity critically influence the aging brain.Understanding these changes is important for maintaining cognitive health,especially given the increasing prevalence of age-related conditions that affect cognition.This review aims to explore the age-induced changes in brain plasticity and molecular processes,differentiating normal aging from the pathogenesis of Alzheimer's disease,thereby providing insights into predicting the risk of dementia,particularly Alzheimer's disease.
基金supported by the National Key Research and Development Program of China(2022YFD2101003)the 111 Project from the Ministry of Education of the People’s Republic of China(B18053).
文摘As people live longer,the burden of aging-related brain diseases,especially dementia,is increasing.Brain aging increases the risk of cognitive impairment,which manifests as a progressive loss of neuron function caused by the impairment of synaptic plasticity via disrupting lipid homeostasis.Therefore,supplemental dietary lipids have the potential to prevent brain aging.This review summarizes the important roles of dietary lipids in brain function from both structure and mechanism perspectives.Epidemiological and animal studies have provided evidence of the functions of polyunsaturated fatty acids(PUFAs)in brain health.The results of interventions indicate that phospholipids—including phosphatidylcholine,phosphatidylserine,and plasmalogen—are efficient in alleviating cognitive impairment during aging,with plasmalogen exhibiting higher efficacy than phosphatidylserine.Plasmalogen is a recognized nutrient used in clinical trials due to its special vinyl ether bonds and abundance in the postsynaptic membrane of neurons.Future research should determine the dose-dependent effects of plasmalogen in alleviating brain-aging diseases and should develop extraction and storage procedures for its clinical application.
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,No.8177051488(to HL).
文摘Oxidative stress is currently considered to be the main cause of brain aging.Astaxanthin can improve oxidative stress under multiple pathological conditions.It is therefore hypothesized that astaxanthin might have therapeutic effects on brain aging.To validate this hypothesis and investigate the underlying mechanisms,a mouse model of brain aging was established by injecting amyloid beta(Aβ)25-35(5μM,3μL/injection,six injections given every other day)into the right lateral ventricle.After 3 days of Aβ25-35 injections,the mouse models were intragastrically administered astaxanthin(0.1 mL/d,10 mg/kg)for 30 successive days.Astaxanthin greatly reduced the latency to find the platform in the Morris water maze,increased the number of crossings of the target platform,and increased the expression of brain-derived neurotrophic factor,synaptophysin,sirtuin 1,and peroxisome proliferator-activated receptor-γ coactivator 1α.Intraperitoneal injection of the sirtuin 1 inhibitor nicotinamide(500μM/d)for 7 successive days after astaxanthin intervention inhibited these phenomena.These findings suggest that astaxanthin can regulate the expression of synaptic proteins in mouse hippocampus through the sirtuin 1/peroxisome proliferator-activated receptor-γcoactivator 1αsignaling pathway,which leads to improvements in the learning,cognitive,and memory abilities of mice.The study was approved by the Animal Ethics Committee,China Medical University,China(approval No.CMU2019294)on January 15,2019.
文摘Aging is well known to be the main risk factor for the neurodegenerative pathologies,in particular,Parkinson’s disease（PD）and Alzheimer’s disease（AD）.In aging and in the diseases,similar changes in various hallmarks of neurodegeneration（lipofuscin accumulation,autophagia weakening,and disturbances in functions of mitochondriaand lysosomes） were shown （Tan et al., 2014）. Furthermore, dopami- nergic system （DAS） involvement in mechanisms of aging, PD, and AD were revealed （Martorana and Koch, 2014）.
基金Project supported by the Natural Science Foundation of Jiangsu Province,China(Grant No.BK20190736)the Young Scientists Fund of the National Natural Science Foundation of China(Grant Nos.81701346 and 61603198)Qinglan Team of Universities in Jiangsu Province(Jiangsu Teacher Letter[2020]10 and Jiangsu Teacher Letter[2021]11).
文摘Characterizing the trajectory of the healthy aging brain and exploring age-related structural changes in the brain can help deepen our understanding of the mechanism of brain aging.Currently,most structural magnetic resonance imaging literature explores brain aging merely from the perspective of morphological features,which cannot fully utilize the grayscale values containing important intrinsic information about brain structure.In this study,we propose the construction of two-dimensional horizontal visibility graphs based on the pixel intensity values of the gray matter slices directly.Normalized network structure entropy(NNSE)is then introduced to quantify the overall heterogeneities of these graphs.The results demonstrate a decrease in the NNSEs of gray matter with age.Compared with the middle-aged and the elderly,the larger values of the NNSE in the younger group may indicate more homogeneous network structures,smaller differences in importance between nodes and thus a more powerful ability to tolerate intrusion.In addition,the hub nodes of different adult age groups are primarily located in the precuneus,cingulate gyrus,superior temporal gyrus,inferior temporal gyrus,parahippocampal gyrus,insula,precentral gyrus and postcentral gyrus.Our study can provide a new perspective for understanding and exploring the structural mechanism of brain aging.
文摘Brain aging is the main manifestation of nervous system senescence, and is clinically represented by reduced learning and memory capacities and slowed reactions. Several studies have shown that Chinese medicines can effectively slow these processes. For example, polysaccharides from Schisandra chinensis have anti-aging effects, while Buyang Huanwu decoction can effectively improve cerebral blood flow and hemorheology,
基金supported by a Grant(2023R1A2C1006622 to MSK)the K-Brain Project(RS-2023-00265515 to MSK)of the National Research Foundation(NRF)funded by the Ministry of Science and ICT(MSIT),Republic of Korea.
文摘Brain aging is a recognized risk factor for neurodegenerative diseases like Alzheimer’s disease,Parkinson’s disease,and amyotrophic lateral sclerosis(ALS,Lou Gehrig’s disease),but the intricate interplay between brain aging and the pathogenesis of these conditions remains inadequately understood.Cellular senescence is considered to contribute to cellular dysfunction and inflammaging.According to the threshold theory of senescent cell accumulation,the vulnerability to neurodegenerative diseases is associated with the rates of senescent cell generation and clearance within the brain.Given the role of microglia in eliminating senescent cells,the accumulation of senescent microglia may lead to the acceleration of brain aging,contributing to inflammaging and increased vulnerability to neurodegenerative diseases.In this review,we propose the idea that the senescence of microglia,which is notably vulnerable to aging,could potentially serve as a central catalyst in the progression of neurodegenerative diseases.The senescent microglia are emerging as a promising target for mitigating neurodegenerative diseases.
基金supported by the National Key R&D Program of China(2021YFA0804900 and 2020YFA0509300)the National Natural Science Foundation of China(82125009,82330045,31871082,91849101,32121002,82071185,and 92149303)+7 种基金the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB39000000)CAS Project for Young Scientists in Basic Research(YSBR-013)Plans for Major Provincial Science&Technology Projects(202303a07020004)the Collaborative Innovation Program of Hefei Science Center,CAS(2022HSC-CIP003)Research Funds of Center for Advanced Interdisciplinary Science and Biomedicine of IHM(QYZD20220003)Anhui Provincial Natural Science Foundation(2208085Y28)National Natural Science Foundation Incubation Program of the Second Affiliated Hospital of Anhui Medical University(2021GMFY02)Translational Medicine Research Foundation of the Second Affiliated Hospital of Anhui Medical University(2022ZHYJ02)。
文摘Age-related cognitive decline and dementia are significant manifestations of brain aging.As the elderly population grows rapidly,the health and socio-economic impacts of cognitive dysfunction have become increasingly significant.Although clinical treatment of dementia has faced considerable challenges over the past few decades,with limited breakthroughs in slowing its progression,there has been substantial progress in understanding the molecular mechanisms and hallmarks of age-related dementia(ARD).This progress brings new hope for the intervention and treatment of this disease.In this review,we categorize the latest findings in ARD biomarkers into four stages based on disease progression:Healthy brain,preclinical,mild cognitive impairment,and dementia.We then systematically summarize the most promising therapeutic approaches to prevent or slow ARD at four levels:Genome and epigenome,organelle,cell,and organ and organism.We emphasize the importance of early prevention and detection,along with the implementation of combined treatments as multimodal intervention strategies,to address brain aging and ARD in the future.
基金supported by the Science and Technology Innovation Program of Hunan Province(2022RC1148)the Natural Science Foundation of Hunan Province(2022JJ31009,2022JJ50260)+4 种基金the Program for Science and Technology of Changsha,China(kh2301028)the Science and Technology Innovation Plan Project of Hunan Province(2023NK2033)the Innovation Leading Plan Project of Hunan Province(2021GK4022)the“Kemen Food”Graduate Science and Technology Innovation Project of Central South University of Forestry and Technology(2023KMCX02)the Graduate Science and Technology Innovation Fund Project of Hunan Province(QL20220182).
文摘Alzheimer’s disease(AD)is a neurodegenerative disorder associated with brain aging,and the accumulation ofβ-amyloid(Aβ)and hyperphosphorylated Tau proteins are key pathological features.Currently,drugs for the treatment of AD are mainly single-targeted,but the complex pathogenesis of AD makes it difficult to achieve the desired results.Therefore,the development of multitargeted therapies is crucial for future interventions.Rice bran oil(RBO)has been recognized as an edible oil with several health benefits,but its effects on AD caused by brain aging remain underexplored.In this study,the effects of RBO on memory dysfunction in D-galactose(D-gal)mice and its molecular mechanisms were investigated via in vivo and in silico methods from the perspective of AD pathologies.Our results suggested that compounds in RBO could modulate the activities of Aβprecursor protein cleaving enzyme 1(BACE1),mitogen-activated protein kinase 3(MAPK3),matrix metalloproteinase 3(MMP3),and intercellular adhesion molecule 1(ICAM1),leading to inhibition of Aβaccumulation and Tau protein hyperphosphorylation.Moreover,RBO reduced Aβ-induced oxidative stress by inhibiting the activity of mouse double minute 2 homolog(MDM2)and cyclic adenosine monophosphate(cAMP)response element binding protein binding protein(CREBBP),and attenuated neuroinflammation by inhibiting the activity of nitric oxide synthase 2(NOS2)and reducing Aβaccumulation and Tau protein hyperphosphorylation.Additionally,α-linolenic acid in RBO exhibited inhibitory effects on D-gal-induced apoptosis in PC12 cells through modulation of NOS2,MDM2,ICAM1,and phospho-extracellular signal-regulated kinase 1/2(p-ERK1/2).Similarly,stigmastanol inhibited apoptosis in D-gal-induced PC12 cells through the regulation of NOS2.Thus,RBO can be considered as a potential functional food to attenuate AD owing to its multicomponent and multitarget effects.
基金Support Program for New Century Excellent Talents in the National Ministry of Education,No. NCET-04-0657Henan Project for cultivation of Innovation Talents in Colleges and Universities No.2004-23
文摘BACKGROUND： The most prominent characteristic of brain aging is decreased learning and memory ability. The functions of learning and memory are closely related to intracerebral acetylcholinesterase （ACHE） and monoamine neurotransmitter activity. Previous studies have shown that Schisandra chinensis polysaccharide has an anti-aging effect. OBJECTIVE： To explore the effects of Schisandra chinensis polysaccharide on AChE activity and monoamine neurotransmitter content, as well as learning and memory ability in a D-galactose-induced aging mouse brain model compared with the positive control drug Kangnaoling. DESIGN, TIME AND SETTING： Completely randomized, controlled experiment based on neurobiochemistry was performed at the Pharmacological Laboratory, Henan University of Traditional Chinese Medicine from September to December 2003. MATERIALS： Schisandra chinensis was purchased from Henan Provincial Medicinal Company. Schisandra chinensis polysaccharide was obtained by water extraction and alcohol precipitation. Kangnaoling pellets were provided by Liaoning Tianlong Pharmaceutical （batch No. 20030804; state drug permit No. H21023095）. A total of 50 six-week-old Kunming mice were randomly divided into five groups： blank control, model, Kangnaoling, high and low dosage Schisandra chinensis polysaccharide groups, with 10 mice per group. METHODS： Mice in the blank control group were subcutaneously injected with 0.5 mL/20 g normal saline into the nape of the neck each day, while the remaining mice were subcutaneously injected with 5% D-galactose saline solution （0.5 mL/20 g） in the nape for 40 days to induce a brain aging model. On day 11, mice in the high and low dosage Schisandra chinensis polysaccharide groups were intragastrically infused with 20 mg/mL and 10 mg/mL Schisandra chinensis polysaccharide solution （0.2 mL/10 g）, respectively. Mice from the Kangnaoling group were intragastrically infused with 35 mg/mL Kangnaoling suspension （0.2 mL/10 g）, and the mice in the model group were intragastrically infused with the same volume of normal saline （0.2 mL/10 g） once per day for 30 consecutive days. MAIN OUTCOME MEASURES： Two hours after the final administration, pathohistological changes in the cerebral cortex and hippocampus were observed using hematoxylin ＆ eosin staining. AChE activity was detected using chromatometry. Monoamine neurotransmitter content was measured using fluorimetry. Learning and memory was measured using the step down test and darkness avoidance test. RESULTS： Both Schisandra chinensis polysaccharide and Kangnaoling improved pathological injury to the cerebral cortex and hippocampus in a mouse model of brain aging. Compared with the blank control group, AChE activity and content of norepinephrine （NA）, dopamine （DA）, and 5-hydroxytryptamine （5-HT） were significantly decreased in the model group （P 〈 0.01 ）. In contrast, AChE activity and NA, DA, and 5-HT levels significantly increased in the Kangnaoling and high dosage Schisandra chinensis polysaccharide groups （P 〈 0.01）, while NA levels significantly increased in the low dosage Schisandra chinensis polysaccharide group （P 〈 0.01）. Drug treatment improved learning and memory abilities （P 〈 0.01 or P 〈 0.05）. CONCLUSION： Schisandra chinensis polysaccharide significantly increased levels of central neurotransmitters and improved learning and memory in a mouse model of brain aging. The effects of Schisandra chinensis polysaccharide were equal to that of Kangnaoling pellets.
文摘The regulation of gene expression in brain vicissitudes during aging is still not much known and explored. Differential gene expression and regulation is a key factor involved to identify the important landmarks within the brain transcriptome to study neuronal aging. Recently</span><span style="font-family:Verdana;">,</span><span style="font-family:Verdana;"> transcriptomic studies are highly explored to understand and depict diseased versus normal as next generation sequencing enable</span><span style="font-family:Verdana;">s</span><span style="font-family:Verdana;"> to capture the complete biological context to the entire genome. Study of gene expression during aging compared to young flies provides a signature and scenario of gene expression and regulation during aging. In this study</span><span style="font-family:Verdana;">,</span><span style="font-family:""><span style="font-family:Verdana;"> we took advantage of NGS raw data of young and old flies head from SRA database of NCBI and decrypted the gene expression regulation during normal aging in drosophila model. We identified 350 genes with significant differential expression between young and old flies having 0.01% FDR. Various pathways in context to identified genes which are involved in aging include autophagy </span><i><span style="font-family:Verdana;">i.e.</span></i><span style="font-family:Verdana;"> cell death and apoptosis, proteolysis</span><span style="font-family:Verdana;">, oxidative</span><span style="font-family:Verdana;"> stress, declination grey and white matter and neurotransmitter levels, mitochondrial discrepancy, electron transport chain, sugar degradation pathways, activation of transcription factors involved in epigenetic changes, regulators involved in negative and positive regulation WNT signaling pathways, G protein coupled receptor etc. as all these factors contribute to neurodegeneration and possibly dementia in normal aging. So, to find the specific genes and regulators which are differentially expressed in normal aging</span></span><span style="font-family:Verdana;">,</span><span style="font-family:Verdana;"> we investigate brain transcriptome of normal aging flies compared to young flies which offer a repertoire of genes, regulators and factors involved in network of neurodegeneration to establish direct correlation between aging and dementia. We also identified the pathways which are involved in aging and corresponding gene regulation in these pathways in aging flies brain. It is found that there are some common pathways whose genes and regulators are highly differentially regulated in both aging and dementia.
基金supported by the Hundred-Talent Program of Chinese Academy of Sciences(Y4065411411100050210)to J.L.+3 种基金the National Natural Science Foundation of China(8147131391649119)to J.L.the National Natural Science Foundation of China(31260242 to)F.Lthe National Science and Technology Infrastructure Program(2014BAI01B01-04)to S.L.
文摘Brain development and aging are associated with alterations in multiple epigenetic systems, including DNA methylation and demethylation patterns. Here, we observed that the levels of the 5- hydroxymethylcytosine （5hmC） ten-eleven transtocation （TET） enzyme-mediated active DNA demethylation products were dynamically changed and involved in postnatal brain development and aging in tree shrews （Tupaia belangeri chinensis）. The levels of 5hmC in multiple anatomic structures showed a gradual increase throughout postnatal development, whereas a significant decrease in 5hmC was found in several brain regions in aged tree shrews, including in the prefrontal cortex and hippocampus, but not the cerebellum. Active changes in Tet mRNA levels indicated that TET2 and TET3 predominantly contributed to the changes in 5hmC levels. Our findings provide new insight into the dynamic changes in 5hmC levels in tree shrew brains during postnatal development and aging processes.
文摘The aging process in mammals is correlated with changes in psychomotor performance, cognitive function, and ability to adapt to stress (Montgomery et al., 1982; Lorens et al., 1990). These changes may be related to alterations in neuronal tissue that occur during the aging process. The normal aging process may be conceived of as the neuronal cell’s increasing inability to maintain normal cellular function which ultimately results in a number of morphological and biochemical changes. Morphologically, there is a loss of neuronal cells with increasing age (Brizzee and
文摘Rats of both sexes were fed on a basal feed containing 1% refined konjac meal (RKM) for 18 months and the effects of RKM on the cell aging were observed. A comparable group fed on the basic feed was used as the control. Results obtained demonstrate that the long-term feeding of RKM to rats can delay the course of cell aging of the gliocyte, cadiomyocyte, and the endothelial cell of the large and medium arteriases, hence it is likely to delay the occurrence of arteriosclerosis and improve the functions of the brain, heart and vascular system.
基金supported by the National Natural Science Foundation of China,No.81373020Beijing Natural Science Foundation of China,No.7112014+1 种基金a grant from the Science and Technology Development Project of Beijing Municipal Education Commission of China,No.KM201110025014a grant from the Beijing Municipal Science and Technology Project of China,No.Z131107002213071
文摘D-galactose has been widely used in aging research because of its efficacy in inducing senescence and accelerating aging in animal models. The present study investigated the benefits of exercise for preventing neurodegeneration, such as synaptic plasticity, spatial learning and memory abilities, in mouse models of aging. D-galactose-induced aging mice were administered daily subcutaneous injections of D-galactose at the base of the neck for 10 consecutive weeks. Then, the mice were subjected to exercise training by running on a treadmill for 6 days a week. Shortened escape latency in a Morris water maze test indicated that exercise improved learning and memory in aging mice. The ameliorative changes were likely induced by an upregulation of Bcl-2 and brain-derived neurotrophic factor, the repression of apoptosis factors such as Fas and Bax, and an increase in the activity of glucose transporters-1 and 4. The data suggest moderate exercise may retard or inhibit neurodegeneration in D-galactose-induced aging mice.
文摘<strong>Objective</strong>: Purpose of this study was to investigate the behavioral and brain activity impairments in patients after moderate traumatic brain injury (mTBI) in comparison with the normal ranges while dual-tasks performing. We would like to evaluate dual-tasking as diagnostic and rehabilitation tool and to test hypothesis of brain aging after mTBI. <strong>Material and Methods</strong>: Electroencephalographic (EEG), stabilographic and clinical study was performed in 11 patients (mean age 28.8 ± 8.4 years) for up to 1 - 12 months after a mTBI in comparison with 17 healthy subjects (26.7 ± 5.1 years). All the participants performed two motor and two cognitive tasks presented separately, and simultaneously (dual-tasking). <strong>Results</strong>: Clinical examination revealed predominantly cognitive deficit in mTBI patients with intact postural control. EEG data demonstrated coherence decrease for slow (delta-theta) rhythms in frontal-temporal areas predominantly for left hemisphere during cognitive tasks performance. In contrast, EEG coherence for slow spectral bands increased in the same areas in healthy volunteers. EEG coherence increased for fast spectral bands—alpha2 and beta, predominantly in right hemisphere while both healthy adults and patients performed motor components of dual tasks. Rehabilitation course with dual tasks, led to a predominant reduction in cognitive deficits, and EEG coherence increases at the frontal-temporal areas of the left hemisphere. <strong>Conclusions</strong>: Dual-tasks may be used as diagnostic tool in patients after mTBI. This approach demonstrates predominant cognitive deficit, and left hemispheric dysfunction in patients similar to elderly persons and support the hypothesis of brain aging after TBI. Pilot studies also suggested rehabilitation effect of dual-tasking in mTBI patients.
文摘BACKGROUND： Prophylactic dietary restriction （DR）, whether lifelong or started in adulthood,retards the aging process and attenuates cognitive decline in rodents. However, whether the anti-aging and neuroprotective efficacy of DR initiate late in life or accompany the aging process remains unclear.OBJECTIVE： The present study sought to： （1） determine if DR could protect against behavioral decline in mice when implemented during the aging process induced by D-galactose and （2） examine neuronal apoptosis in these aged brains and whether DR could block apoptosis.DESIGN, TIME AND SETTING： The randomized controlled animal study. The experiment was performed at the Experimental Animal Center of Capital Medical University and the Laboratory Center of School of Public Health of Captial Medical University of China from April 2006 to October 2007.MATERIALS： D-galactose （D-gal） was purchased from Beijing Chemical-Regent Company （Beijing, China）. Terminal transferase dUTP nick end labeling （TUNEL） detection kit was obtained from Roche, Germany. Assay kits for antioxidant enzyme activities and malondialdehyde contents were purchased from Jiancheng Institute of Biotechnology （Nanjing, China）. Morris water maze （Friends Honesty Life Sciences Co. Ltd., Hong Kong, China） and Flow Cytometry （Coulter, USA） were used in this study.METHODS： A total of 40 male Institute of Cancer Research （lCR） mice, 3 months old, were equally and randomly divided into D-gal treatment, DR treatment, D-gal ＋ DR treatment and normal control groups, and were then randomly assigned to one of two feeding regimens： ad libitum access to food or DR which received a 70% amount of daily food intake as that by ad libitum fed mice. There were two replicates per feeding regimen and mice were fed for 10 weeks,with or without a daily subcutaneous injection of D-gal at 100 mg/kg.MAIN OUTCOME MEASURES： Animals＇ spatial learning and memory performance were tested in the Morris water maze. Neuronal apoptosis rates were evaluated by Annexin V/flow cytometry assay and TUNEL assay. Lipid peroxidation levels and antioxidant defense capacity of the brain were measured using testing kits.RESULTS： DR markedly reduced the prolonged escape latency of D-gal mice in the water maze test （P〈0.01）. Annexin V and TUNEL assays showed that the D-gal mice had a significant higher percentage of neuronal apoptosis compared with normal control mice （P〈0.05）, and that DR treatment markedly decreased this apoptotic cell death （P〈0.05）. DR also reversed the decline of total superoxide dismutase and glutathione peroxidase activities and the increase of malondialdehyde levels in the brain of D-gal mice （P〈0.05, respectively）.CONCLUSION： DR reduces the impact of D-gal-induced brain aging in mice and can reverse performance decline and neurobiochemical impairments. These results demonstrate that implementation of DR in conditions of chronic oxidative stress can be neuroprotective, and that senium DR can be beneficial for healthy aging.
基金supported by the Priority Research Program of the Ministry of Science and Technology of the People’s Republic of China(Grant Nos.2017YFA0504600)the National Natural Science Foundation of the People’s Republic of China(Grants Nos.91649103,32091159).
文摘One of the basic questions in the aging field is whether there is a fundamental difference between the aging of lower invertebrates and mammals.A major difference between the lower invertebrates and mammals is the abundancy of noncoding RNAs,most of which are not conserved.We have previously identified a noncoding RNA Terc-53 that is derived from the RNA component of telomerase Terc.To study its physiological functions,we generated two transgenic mouse models overexpressing the RNA in wild-type and early-aging Terc^(−/−)backgrounds.Terc-53 mice showed age-related cognition decline and shortened life span,even though no developmental defects or physiological abnormality at an early age was observed,indicating its involvement in normal aging of mammals.Subsequent mechanistic study identified hyaluronan-mediated motility receptor(Hmmr)as the main effector of Terc-53.Terc-53 mediates the degradation of Hmmr,leading to an increase of inflammation in the affected tissues,accelerating organismal aging.adeno-associated virus delivered supplementation of Hmmr in the hippocampus reversed the cognition decline in Terc-53 transgenic mice.Neither Terc-53 nor Hmmr has homologs in C.elegans.Neither do arthropods express hyaluronan.These findings demonstrate the complexity of aging in mammals and open new paths for exploring noncoding RNA and Hmmr as means of treating age-related physical debilities and improving healthspan.
