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Unraveling brain aging through the lens of oral microbiota

Neural Regeneration Research 2025年第7期20卷 1930-1943页

作者： Qinchao Hu Si Wang Weiqi Zhang Jing Qu Guang-Hui Liu State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijingChina Hospital of Stomatology Guanghua School of StomatologyGuangdong Provincial Key Laboratory of StomatologySun Yat-sen UniversityGuangzhouGuangdong ProvinceChina Advanced Innovation Center for Human brain Protection and National Clinical Research Center for Geriatric Disorders Xuanwu HospitalCapital Medical UniversityBeijingChina aging Translational Medicine Center International Center for Aging and CancerBeijing Municipal Geriatric Medical Research CenterXuanwu HospitalCapital Medical UniversityBeijingChina CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijingChina University of Chinese Academy of Sciences BeijingChina Institute for Stem Cell and Regeneration Chinese Academy of SciencesBeijingChina aging Biomarker Consortium BeijingChina State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijingChina Beijing Institute for Stem Cell and Regenerative Medicine BeijingChina

The oral cavity is a complex physiological community encompassing a wide range of *** 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 *** studies have highlighted how oral microbes might be involved in brain aging and neurodegeneration,indicating potential avenues for intervention *** 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 *** also highlight advances in therapeutic development grounded in the realm of oral microbes,with the goal of advancing brain health and promoting healthy aging.

关键词： Alzheimer's disease brain aging multiple sclerosis neurodegeneration neurodegenerative diseases oral microbiota Parkinson's disease periodontitis bacteria Porphyromonas gingivalis

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Decoding molecular mechanisms:brain aging and Alzheimer's disease

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Neural Regeneration Research 2025年第8期20卷 2279-2299页

作者： Mahnoor Hayat Rafay Ali Syed Hammad Qaiser Mohammad Uzair Khalid Al-Regaiey Roaa Khallaf Lubna Abdullah Mohammed Albassam Imdad Kaleem Xueyi Wang Ran Wang Mehwish SBhatti Shahid Bashir Atta-ur-Rahman School of Applied Biosciences(ASAB) National University of Sciences and Technology(NUST)IslamabadPakistan Department of Biotechnology Quaid-i-Azam UniversityIslamabadPakistan Department of Biological Sciences Faculty of Basic&Applied SciencesInternational Islamic University Islamabad(IIUI)IslamabadPakistan Department of Bioengineering King Fahd University of Petroleum and MineralsDhahranSaudi Arabia Department of Physiology College of MedicineKing Saud UniversityRiyadhSaudi Arabia Department of Neurology Neuroscience CenterKing Fahad Specialist HospitalDammamSaudi Arabia Department of Mental Health Neuroscience CenterKing Fahad Specialist HospitalDammamSaudi Arabia Department of Biosciences Commission on Science and Technology for Sustainable Development in the South(COMSATS University)IslamabadPakistan Department of Psychiatry The First Hospital of Hebei Medical UniversityShijiazhuangHebei ProvinceChina Mental Health Institute of Hebei Medical University ShijiazhuangHebei ProvinceChina Department of Neurobiology and Behavior University of CaliforniaIrvineCAUSA Neuroscience Center King Fahad Specialist Hospital DammamDammamSaudi Arabia

The complex morphological,anatomical,physiological,and chemical mechanisms within the aging brain have been the hot topic of research for *** 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 *** these observable,mild morphological shifts,significant functional modifications in neurotransmission and neuronal activity critically influence the aging *** these changes is important for maintaining cognitive health,especially given the increasing prevalence of age-related conditions that affect *** 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.

关键词： Alzheimer’s disease brain aging cognitive health dementia molecular mechanisms neuronal activity neuroplasticity neurotransmission

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Dietary Lipid Intervention in the Prevention of brain aging

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Engineering 2024年第6期37卷 128-137页

作者： Wei Xiong Bing Fang Xiaoyu Wang Ming Zhang Min Du Jiazeng Sun Juan Chen Yixuan Li Changhao Sun Xingen Lei Xue Zhang Fazheng Ren Key Laboratory of Precision Nutrition and Food Quality Department of Nutrition and HealthChina Agricultural UniversityBeijing 100083China Key Laboratory of Functional Dairy Co-Constructed by the Ministry of Education and Beijing MunicipalityCollege of Food Science and Nutritional EngineeringChina Agricultural UniversityBeijing 100083China School of Food Science and Chemical Engineering Beijing Technology and Business UniversityBeijing 100048China Department of Animal Science Washington State UniversityPullmanWA 99164USA Department of Nutrition and Food Hygiene School of Public HealthHarbin Medical UniversityHarbin 150028China Department of Animal Science Cornell UniversityIthacaNY 14853USA National Health Commission(NHC)and Chinese Academy of Medical Sciences(CAMS)Key Laboratory of Molecular Probe and Targeted Theranostics Harbin Medical UniversityHarbin 150028China

As people live longer,the burden of aging-related brain diseases,especially dementia,is *** 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 ***,supplemental dietary lipids have the potential to prevent brain *** review summarizes the important roles of dietary lipids in brain function from both structure and mechanism *** and animal studies have provided evidence of the functions of polyunsaturated fatty acids(PUFAs)in brain *** 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 *** is a recognized nutrient used in clinical trials due to its special vinyl ether bonds and abundance in the postsynaptic membrane of *** 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.

关键词： brain aging Nutritional intervention Phospholipids Phosphatidylcholine Phosphatidylserine Plasmalogen

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Two-dimensional horizontal visibility graph analysis of human brain aging on gray matter

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Chinese Physics B 2023年第7期32卷 558-563页

作者：倪黄晶杜若瑜梁磊花玲玲朱丽华秦姣龙 School of Geographic and Biologic Information Nanjing University of Posts and TelecommunicationsNanjing 210003China Smart Health Big Data Analysis and Location Services Engineering Laboratory of Jiangsu Province Nanjing 210003China Department of Psychiatry the Affiliated Brain Hospital of Nanjing Medical UniversityNanjing 210029China Jiangsu Health Vocational College Nanjing 211800China School of Computer Science and Engineering Nanjing University of Science and TechnologyNanjing 210094China

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 ***,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 *** this study,we propose the construction of two-dimensional horizontal visibility graphs based on the pixel intensity values of the gray matter slices *** network structure entropy(NNSE)is then introduced to quantify the overall heterogeneities of these *** results demonstrate a decrease in the NNSEs of gray matter with *** 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 *** 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 *** study can provide a new perspective for understanding and exploring the structural mechanism of brain aging.

关键词： two-dimensional horizontal visibility graph brain aging structural magnetic resonance imaging network structure entropy

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Astaxanthin alleviates pathological brain aging through the upregulation of hippocampal synaptic proteins

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Neural Regeneration Research 2021年第6期16卷 1062-1067页

作者： Ning Liu Liang Zeng Yi-Ming Zhang Wang Pan Hong Lai Department of Human Anatomy College of Basic MedicineChina Medical UniversityShenyangLiaoning ProvinceChina Department of Radiology The First Affiliated Hospital of Jinzhou Medical UniversityJinzhouLiaoning ProvinceChina Department of Human Anatomy College of Basic MedicineShenyang Medical CollegeShenyangLiaoning ProvinceChina Department of Neurobiology of Jinzhou Medical University JinzhouLiaoning ProvinceChina

Oxidative stress is currently considered to be the main cause of brain *** can improve oxidative stress under multiple pathological *** is therefore hypothesized that astaxanthin might have therapeutic effects on brain *** 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 *** 3 days of Aβ25-35 injections,the mouse models were intragastrically administered astaxanthin(0.1 mL/d,10 mg/kg)for 30 successive *** 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 *** 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 *** study was approved by the Animal Ethics Committee,China Medical University,China(approval ***2019294)on January 15,2019.

关键词： brain aging cognitive factor hippocampus learning memory oxidative stress pathways synapse

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Microglia in brain aging:An overview of recent basic science and clinical research developments

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Journal of Biomedical Research 2024年第2期38卷 122-136页

作者： Haixia Fan Minheng Zhang Jie Wen Shengyuan Wang Minghao Yuan Houchao Sun Liu Shu Xu Yang Yinshuang Pu Zhiyou Cai Chongqing Medical University Chongqing 400042China Department of Neurology Chongqing General HospitalChongqing 400013China Chongqing Key Laboratory of Neurodegenerative Diseases Chongqing 400013China Department of Neurology the First Hospital of Shanxi Medical UniversityTaiyuanShanxi 030001China Department of Gerontology the First People's Hospital of JinzhongJinzhongShanxi 030009China

aging is characterized by progressive degeneration of tissues and organs,and it is positively associated with an increased mortality *** 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 *** changes collectively contribute to cognitive *** is also a key risk factor for neurodegenerative diseases,such as Alzheimer's disease and Parkinson's *** many years,neurodegenerative disease investigations have primarily focused on neurons,with less attention given to microglial ***,recently,microglial homeostasis has emerged as an important mediator in neurological disease ***,we provide an overview of brain aging from the perspective of the *** 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.

关键词： microglia brain aging Alzheimer's disease Parkinson's disease Huntington's disease

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Targeting on calcium overload mediated brain aging and PD

Targeting on calcium overload mediated brain aging and PD

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中国神经科学学会第十二届全国学术会议

作者： Rong Cai Lei Liu Center of Stroke Beijing Institute for Brain Disorders Capital Medical University

Objective brain aging associates with increasing intracellular calcium and decreasing brain energy. These two processes are likely correlated. For instance, calcium overload may trigger mitochondrial fragmentation which decreases its energy production. As a feedback, decreased energy output results in failure to maintain calcium gradients across the membrane and promotes calcium overload. Therefore, calcium overload and energy failure together may accelerate brain aging（accelerated aging hypothesis）. Our previous study demonstrated that Miro/Vimar complex served as a mediator of calcium overload and mitochondrial fragmentation. Miro is a small GTPase, well known for its function to regulate mitochondrial morphology and transportation. Vimar is the guanine nucleotide exchange factor of Miro that we identified in Drosophila. The mammalian homolog of Vimar is RAP1 GDS1. Methods To test the accelerated aging hypothesis, we generated transgenic flies to overload calcium and performed genetic manipulation on Miro/Vimar complex. In rodent Parkinson disease（PD） models, energy failure due to mitochondrial dysfunction has been well known to play a key pathophysiological role. Therefore, we select to target energy failure in PD to test the potential application of the hypothesis. To restore cellular energy, our previous study showed that terazosin（TZ） can activate glycolysis in vitro. Here, we tested whether TZ might act as a neuroprotective agent in rodent models of PD. Results 1) Calcium overload in the transgenic flies（overexpressed a leaky cation channel） reduced their locomotion ability, but no lifespan reduction, indicating calcium overload may enhance dementia in flies. 2) TZ could promote aerobic glycolysis and energy recovery in mouse brain in vivo. TZ showed strong rescue effects against the MPTP induced PD models in mice and the 6-OHDA induced PD model in rats. Conclusion Accelerated aging hypothesis is supported by our current results, but more work is still needed

关键词： Mitochondrial dysfunction Parkinson’s disease Energy failure Calcium overload brain aging Terazosin Aerobic glycolysis Miro/Vimar Drosophila genetics

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Effect of Schisandra chinensis polysaccharide on intracerebral acetylcholinesterase and monoamine neurotransmitters in a D-galactose-induced aging brain mouse model

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Neural Regeneration Research 2009年第9期4卷 687-693页

作者： Mingsan Miao Jianlian Gao Guangwei Zhang Xiao Ma Ying Zhang Henan University of Traditional Chinese Medicine Zhengzhou 450008 Henan Province China Henan Provincial Institute of Food and Drug Control Zhengzhou 450008 Henan Province China

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 m

关键词： Schisandra chinensis polysaccharide D-galactose brain aging neurotransmitter acetylcholine esterase

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Mitochondrial protein sulfenation during aging in the rat brain

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Biophysics Reports 2018年第2期4卷 104-113页

作者： Xiaorong Yang Jinzi Wu Siqun Jing Michael J.Forster Liang-Jun Yan Department of Pharmaceutical Sciences UNT System College of Pharmacy University of North Texas Health Science Center Center for Neuroscience Discovery Institute for Healthy Aging University of North Texas Health Science Center Department of Physiology National Key Disciplines Key Laboratory for Cellular Physiology of Ministry of Education Shanxi Medical University College of Life Sciences and Technology Xinjiang University

There is accumulating evidence that cysteine sulfenation(cys-SOH) in proteins plays an important role in cellular response to oxidative stress. The purpose of the present study was to identify mitochondrial proteins that undergo changes in cys-SOH during aging. Studies were conducted in rats when they were5 or 30 months of age. Following blocking of free protein thiols with N-ethylmaleimide, protein sulfenic acids were reduced by arsenite to free thiol groups that were subsequently labeled with biotinmaleimide. Samples were then comparatively analyzed by two-dimensional Western blots, and proteins showing changes in sulfenation were selectively identified by mass spectrometry peptide *** a result, five proteins were identified. Proteins showing an age-related decrease in sulfenation include pyruvate carboxylase and pyruvate dehydrogenase; while those showing an age-related increase in sulfenation include aconitase, mitofilin, and tubulin(a-1). Results of the present study provide a general picture of mitochondrial protein sulfenation in brain oxidative stress and implicate the involvement of protein sulfenation in overall decline of mitochondrial function during brain aging.

关键词： brain aging Mitochondria Oxidative stress Sulfenation Two-dimensional polyacrylamide gel electrophoresis (2D-PAGE)

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Insilico Identification of Genes and Molecular Pathways during aging in <i>Drosophila</i>brain

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Advances in aging Research 2021年第4期10卷 78-96页

作者： Arpita Parakh Deovrat Begde Naveen Dhingra Institute of Biological Science SAGE University Indore India Department of Biochemistry and Biotechnology Dr. Ambedkar College Deeksha Bhoomi Nagpur India

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, transcriptomic studies are highly explored to understand and depict diseased versus normal as next generation sequencing enables 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, 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 i.e. cell death and apoptosis, proteolysis, oxidative 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 d

关键词： Neurodegeneration brain aging Dementia Gene Regulation Pathways

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