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Functional aspects of the brain lymphatic drainage system in Aging and neurodegenerative diseases

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Journal of Biomedical Research 2024年第3期38卷 206-221页

作者： Yan Chen Xiaoxin He Jiachen Cai Qian Li Jiangsu Key Laboratory of Neurodegeneration Nanjing Medical UniversityNanjingJiangsu 211166China Shandong Institute of Brain Science and Brain-inspired Research Shandong First Medical University&Shandong Academy of Medical SciencesJinanShandong 250117China Center for Global Health Nanjing Medical UniversityNanjingJiangsu 211166China

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.

关键词： glymphatic system meningeal lymphatic vessels Aging neurodegenerative diseases nonpharmacological therapies

Effect of in-situ formed Al hydrates through long-term Aging on enhanced particle destabilization by PACl coagulation

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Journal of Environmental Sciences 2020年第6期32卷 200-210页

作者： Jr Lin Lin Aldeno Rachmad Ika Chun Chen Tseng Department of Environmental Engineering Chung Yuan Christian UniversityChinese Taipei

Aging of polyaluminum chloride(PACl) coagulants could significantly influence hydrolyzed Al speciation ruling coagulation performance.The goal of this study was to investigate Al species transformation through long-term Aging and its impact on coagulation performance.Two kinds of commercial coagulants(PACl-1 and PACl-2) were stored for in-situ Aging tests in six months to evaluate Al species variation with time and the performance of coagulation with natural turbid waters.The results showed that CaSO4 precipitation easily occur in a commercial PACl coagulant with time as it contains SO4^2- and Ca^2+.It also activates the precipitation of gibbsite Al(OH)3 in PACl with Aging.Through 180 days Aging,both monomeric Al(Ala) and polymeric Al(Alb) substantially transform into colloidal Al(Alc) and precipitated for both PACl coagulants.At low turbidity(10 NTU),PACl-1 has a superior turbidity reduction rate than PACl-2,while PACl-2 performs a little better turbidity re duction at high turbidity(1000 NTU) regardless of Aging time.With Aging time,an obvious decrease in turbidity reduction for PACl-1 coagulation is observed at low turbidity of 10 NTU,while the improvement in turbidity reduction for PACl-2 coagulation by enhanced sweep flocculation can be achieved as Alb mostly transform into Alc after 150 days Aging.It is concluded that dominant in-situ formed Alc after a long time hydrolysis can improve PACl coagulation efficiency in turbidity reduction by enhanced sweep flocculation,especially for low turbidity water,but the increase in preformed Alc in PACl would worsen particle destabilization after Aging.

关键词： Coagulation PACl Aging Al hydrates

Multimodal Omics Approaches to Aging and Age‑Related Diseases

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Phenomics

Phenomics 2024年第1期4卷 56-71页

作者： Qianzhao Ji Xiaoyu Jiang Minxian Wang Zijuan Xin Weiqi Zhang Jing Qu Guang‑Hui Liu State Key Laboratory of Membrane Biology Instituteof ZoologyChinese Academy of SciencesBeijing 100101China State Key Laboratory of Stem Cell and ReproductiveBiology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Key Laboratory of Organ Regeneration and Reconstruction Institute of ZoologyChinese Academy of SciencesBeijing 100101China CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academyof Sciences and China National Center for BioinformationBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China Institute for Stem Cell and Regeneration Chinese Academyof SciencesBeijing 100101China Beijing Institute for Stem Cell and Regenerative Medicine Beijing 100101China School of Future Technology University of ChineseAcademy of SciencesBeijing 100190China Advanced Innovation Center for Human Brain Protection National Clinical Research Center for GeriatricDisordersXuanwu Hospital Capital Medical UniversityBeijing 100053China Aging Translational Medicine Center International Centerfor Aging and CancerXuanwu HospitalCapital MedicalUniversityBeijing 100053China

Aging is associated with a progressive decline in physiological capacities and an increased risk of Aging-associated disorders.An increasing body of experimental evidence shows that Aging is a complex biological process coordinately regulated by multiple factors at diferent molecular layers.Thus,it is difcult to delineate the overall systematic Aging changes based on single-layer data.Instead,multimodal omics approaches,in which data are acquired and analyzed using complementary omics technologies,such as genomics,transcriptomics,and epigenomics,are needed for gaining insights into the precise molecular regulatory mechanisms that trigger Aging.In recent years,multimodal omics sequencing technologies that can reveal complex regulatory networks and specifc phenotypic changes have been developed and widely applied to decode Aging and age-related diseases.This review summarizes the classifcation and progress of multimodal omics approaches,as well as the rapidly growing number of articles reporting on their application in the feld of Aging research,and outlines new developments in the clinical treatment of age-related diseases based on omics technologies.

关键词： Multimodal omics approaches Aging Genome Epigenome

Studies on the anti-Aging properties of bovine whey supplementation on reproductive hormonal profiles and sperm structure and function of adult and senile rats

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Food Bioscience 2022年第1期45卷 301-312页

作者： Norhan TAH.Kandil Dalia AA.Sabry Nermeen IE.Ashry Hassan IH.El-Sayyad Zoology Department Faculty of ScienceMansoura UniversityEgypt

The purpose of this study was to investigate how well whey might protect against Aging related alterations in sperm structure,seminal and antioxidant enzymes and serum hormonal profiles.Male Wistar albino rats aged 8 and 30-months were divided into two primary groups with or without whey supplementation(n=8).After the experiments of whey supplementation,the rats were euthanized,blood was collected,and serum was separated.Sperm ultrastructure and flow cytometry of annexin-V and mitochondrial membrane potential were carried out.Seminal antioxidant and malondialdehyde concentrations were determined.Serum hormonal profiles of testosterone,growth(GH),follicle stimulating hormone(FSH),luteinizing hormone(LH)and thyroid stimulating hormone(TSH)as well as pituitary gland ultrastructure were investigated.Results showed that whey supplementation improved the structure and function of sperm and seminal fluid as well as the serum hormonal levels of adult.In aged rats,whey supplementation increased the serum levels of GH,FSH,LH and TSH as well as seminal superoxide dismutase.Whey supplementation also caused reduction of seminal alkaline and acid phosphatases and lipid peroxidation in aged rat compared to that in adult ones.They also improved sperm motility and viability but reduced sperm abnormalities by increasing sperm mitochondrial membrane potential and lowering annexin v levels.In conclusion,whey contains antioxidant components that alleviated oxidative stress involved in damAging sperm macromolecules during Aging process.

关键词： Aging Sperm Seminal fluid Pituitary Hormones

Antioxidant effect of Lactobacillus fermentum HFY02-fermented soy milk on D-galactose-induced Aging mouse model

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Food Science and Human Wellness 2022年第5期11卷 1362-1372页

作者： Tiantian Hu Rui Chen Yu Qian Ke Ye Xingyao Long Kun-Young Park Xin Zhao Chongqing Collaborative Innovation Center for Functional Food Chongqing Engineering Research Center of Functional FoodChongqing Engineering Laboratory for Research and Development of Functional FoodChongqing University of EducationChongqing 400067China Department of General Practice The Third People's Hospital of ChengduChengdu 610036China Department of Food Science and Biotechnology Cha UniversitySeongnam 13488Korea

This study aimed to investigate the antioxidant effect of soybean milk fermented by a new type of Lactobacillus fermentum(LF-HFY02)by using D-galactose induced Aging mice model.Firstly,the optimal fermentation conditions was screened out by detecting the effects of different fermentation temperature and time on the active components and antioxidant activity of soybean milk in viro.And then unfermented soybean milk and the soybean milk fermented by different Lactobacillus was given by gavage to D-galactose-induced Aging mouse.The activities of GSH,GSH-Px,SOD,CAT and T-AOC in serum,brain and liver of soybean milk fermented by LF-HFY02 were significantly increased,while the content of MDA and the level of AGEs in hippocampal were significantly decreased compared with D-galactose induced group.Further more,the mRNA expression of GSH and SOD in mouse liver were obviously up-regulated by soybean milk fermented by LF-HFY02.The skin tissue structure of mice in the LF-HFY02 fermented soybean milk group was more complete,the collagen fibers were increased and arranged orderly and liver inflammation has improved compared with the model group.And Western blot analysis showed that LF-HFY02 effectively upregulated EGFR,SOD and GSH protein expression in mouse liver.These findings suggest that LF-HFY02 can effectively prevent D-galactose-induced oxidation and Aging in mice,and the effect was even better than that of the Lactobacillus delbruechii subsp.bulgaricus and vitamin C.Thus,LF-HFY02 may be potentially employed as a probiotic strain.In conclusion,soybean milk fermented by LF-HFY02 can increase the content of antioxidant factors and the activity of antioxidant enzymes by regulating gene and protein expression,and finally inhibit the process of tissue cell peroxidation,and improve the oxidative damage of mouse skin and liver.The results could provide a basis for the research and development and industrial production of probiotic-related fermented soybean milk products.

关键词： Lactobacillus fermentum HFY02 Fermented soybean milk D-galactose Antioxidant Aging

Aging amorphous/crystalline heterophase PdCu nanosheets for catalytic reactions

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National Science Review 2019年第5期6卷 955-961页

作者： Hongfei Cheng Nailiang Yang Xiaozhi Liu Qinbai Yun Min Hao Goh Bo Chen Xiaoying Qi Qipeng Lu Xiaoping Chen Wen Liu Lin Gu Hua Zhang Center for Programmable Materials School of Materials Science and EngineeringNanyang Technological University State Key Laboratory of Biochemical Engineering Institute of Process Engineering Chinese Academy of Sciences Beijing National Laboratory for Condensed Matter Physics Institute of Physics Chinese Academy of Sciences School of Physical Sciences University of Chinese Academy of Sciences Singapore Institute of Manufacturing Technology A*STAR School of Materials Science and Engineering University of Science and Technology Beijing School of Chemical and Biomedical Engineering Nanyang Technological University Songshan Lake Materials Laboratory Department of Chemistry City University of Hong Kong

Phase engineering is arising as an attractive strategy to tune the properties and functionalities of nanomaterials.In particular, amorphous/crystalline heterophase nanostructures have exhibited some intriguing properties.Herein, the one-pot wet-chemical synthesis of two types of amorphous/crystalline heterophase Pd Cu nanosheets is reported, in which one is amorphous phase-dominant and the other one is crystalline phase-dominant.Then the Aging process of the synthesized Pd Cu nanosheets is studied, during which their crystallinity increases, accompanied by changes in some physicochemical properties.As a proof-of-concept application, their Aging effect on catalytic hydrogenation of 4-nitrostyrene is investigated.As a result, the amorphous phase-dominant nanosheets initially show excellent chemoselectivity.After Aging for 14 days, their catalytic activity is higher than that of crystalline phase-dominant nanosheets.This work demonstrates the intriguing properties of heterophase nanostructures, providing a new platform for future studies on the regulation of functionalities and applications of nanomaterials by phase engineering.

关键词： amorphous/crystalline heterophase nanosheets Aging selective hydrogenation catalysis

Single-nucleus transcriptomic landscape of primate hippocampal Aging

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Protein & Cell 2021年第9期12卷 695-716页

作者： Hui Zhang Jiaming Li Jie Ren Shuhui Sun Shuai Ma Weiqi Zhang Yang Yu Yusheng Cai Kaowen Yan Wei Li Baoyang Hu Piu Chan Guo-Guang Zhao Juan Carlos Izpisua Belmonte Qi Zhou Jing Qu Si Wang Guang-Hui Liu State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Advanced Innovation Center for Human Brain Protection National Clinical Research Center for Geriatric DisordersXuanwu Hospital Capital Medical UniversityBeijing 100053China CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of SciencesBeijing 100101China Institute for Stem Cell and Regeneration Chinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China China National Center for Bioinformation Beijing 100101China Aging Translational Medicine Center Xuanwu HospitalCapital Medical UniversityBeijing 100053China Department of Neurosurgery Xuanwu HospitalCapital Medical UniversityBeijing 100053China Sino Danish CollegeUniversity of Chinese Academy of SciencesBeijing 101408China Sino Danish Center for Education and ResearchBeijing 101408China Department of Obstetrics and Gynecology Center for Reproductive MedicinePeking University Third HospitalBeijing 100191China Beijing Institute for Stem Cell and Regenerative Medicine Beijing 100101China Stem Cell Research Center Peking University Third HospitalBeijing 100191China Gene Expression Laboratory Salk Institute for Biological StudiesLa JollaCAUSA

The hippocampus plays a crucial role in learning and memory,and its progressive deterioration with age is functionally linked to a variety of human neurodegenerative diseases.Yet a systematic profiling of the Aging effects on various hippocampal cell types in primates is still missing.Here,we reported a variety of new Aging-associated phenotypic changes of the primate hippocampus.These include,in particular,increased DNA damage and heterochromatin erosion with time,alongside loss of proteostasis and elevated inflammation.To understand their cellular and molecular causes,we established the first single-nucleus transcriptomic atlas of primate hippocampal Aging.Among the 12 identified cell types,neural transiently amplifying progenitor cell(TAPC)and microglia were most affected by Aging.In-depth dissection of gene-expression dynamics revealed impaired TAPC division and compromised neuronal function along the neurogenesis trajectory;additionally elevated pro-inflammatory responses in the aged microglia and oligodendrocyte,as well as dysregulated coagulation pathways in the aged endothelial cells may contribute to a hostile microenvironment for neurogenesis.This rich resource for understanding primate hippocampal Aging may provide potential diagnostic biomarkers and therapeutic interventions against age-related neurodegenerative diseases.

关键词： Aging hippocampus primate single-cell RNA sequencing

Evolution in physiochemical and cloud condensation nuclei activation properties of crop residue burning particles during photochemical Aging

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Journal of Environmental Sciences 2019年第3期31卷 43-53页

作者： Yan Ma Chao Chen Junfeng Wang Youling Jiang Zewen Zheng Hui Chen Jun Zheng Collaborative Innovation Center of Atmospheric Environment and Equipment Technology Nanjing University of Information Science and Technology Harvard-NUIST Joint Laboratory for Air Quality and Climate (JLAQC) Nanjing University of Information Science and Technology NUIST Reading Academy Nanjing University of Information Science and Technology

As a main form of biomass burning in agricultural countries, crop residue burning is a significant source of atmospheric fine particles. In this study, the Aging of particles emitted from the burning of four major crop residues in China was investigated in a smog chamber.The particle size distribution, chemical composition and cloud condensation nuclei(CCN)activity were simultaneously measured. The properties of crop residue burning particles varied substantially among different fuel types. During Aging, the particle size and mass concentration increased substantially, suggesting condensational growth by formation of secondary aerosols. The particle composition was dominated by organics. Aging resulted in considerable enhancement of organics and inorganics, with enhancement ratios of 1.24–1.44 and 1.33–1.76 respectively, as well as a continuous increase in the oxidation level of organics. Elevated CCN activity was observed during Aging, with the hygroscopicity parameter κ varying from 0.16 to 0.34 for fresh particles and 0.19 to 0.40 for aged particles.Based on the volume mixing rule, the hygroscopicity parameter of organic components(κorg) was derived. κorgexhibited an increasing tendency with Aging, which was generally consistent with the tendency of the O:C ratio, indicating that the oxidation level was related to the hygroscopicity and CCN activity of organic aerosols from crop residue burning. Our results indicated that photochemical Aging could significantly impact the CCN activation of crop burning aerosols, not only by the production of secondary aerosols, but also by enhancing the hygroscopicity of organic components, thereby contributing to the aerosol indirect climate forcing.

关键词： Crop residue burning Aging Cloud condensation nuclei activity Hygroscopicity Organic aerosol

Aging-independent and size-dependent genotoxic response induced by titanium dioxide nanoparticles in mammalian cells

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Journal of Environmental Sciences 2019年第11期31卷 94-106页

作者： Juan Wang Jingjing Wang Yun Liu Yaguang Nie Bo Si Tong Wang Ahmed Waqas Guoping Zhao Meimei Wang An Xu Key Laboratory of High Magnetic Field and Ion Beam Physical Biology Chinese Academy of Sciences Anhui Province Key Laboratory of Environmental Toxicology and Pollution Control Technology Hefei Institutes of Physical Science Chinese Academy of Sciences Hefei Anhui 230031 P.R.China University of Science and Technology of China Hefei Anhui 230026 P.R.China Department of Pathophysiology Anhui Medical University Hefei Anhui 230032 P.R.China Institutes of Physical Science and Information Technology Anhui University Hefei Anhui 230601 P.R.China

Titanium dioxide nanoparticles (TiO2 NPs) are subjected to various transformation processes (chemical,physical and biological processes) in the environment,potentially affecting their bioavailability and toxic properties.However,the size variation of TiO2 NPs during Aging process and subsequent effects in mammalian cells are largely unknown.The aim of this study was to illustrate the adverse effects of TiO2 NPs in different sizes (5,15 and Aging process on human-hamster hybrid (AL) cells.There was an Aging-time dependent enhancement of average hydrodynamic size in TiO2 NPs stock suspensions.The cytotoxicity of fresh TiO2 NPs increased in a size-dependent manner;in contrast,their genotoxicity decreased with the increasing sizes of NPs.No significant toxicity difference was observed in cells exposed to either fresh or 60 day-aged TiO2 NPs.Both Fresh and aged TiO2 NPs efficiently induced mitochondrial dysfunction and activated Caspase-3/7 in a size-dependent manner.Using mitochondrial-DNA deficient (ρ°) AL cells,we further discovered that mitochondrial dysfunction made significant contribution to the size-dependent toxicity induced by TiO2 NPs during the Aging process.Taken together,our data indicated that TiO2 NPs could significantly induced the cytotoxicity and genotoxicity in an Aging time-independent and size-dependent manner,which were triggered by mitochondrial dysfunction.Our study suggested the necessity to include size as an additional parameter for the cautious monitoring of TiO2 NPs disposal before entering the environment.

关键词： TiO2 NPs Aging process Human-hamster hybrid (AL) cells Mitochondria Size-effects