title: Quantitative protein profiling of hippocampus during human aging.
abstract: The hippocampus appears commonly affected by aging and various neurologic disorders in humans, whereas little is known about age-related change in overall protein expression in this brain structure. Using the 4-plex tandem mass tag labeling, we carried out a quantitative proteomic study of the hippocampus during normal aging using postmortem brains from Chinese subjects. Hippocampal samples from 16 subjects died of non-neurological/psychiatric diseases were divided into 4 age groups: 22-49, 50-69, 70-89, and >90. Among 4582 proteins analyzed, 35 proteins were significantly elevated, whereas 25 proteins were downregulated, along with increasing age. Several upregulated proteins, including transgelin, vimentin, myosin regulatory light polypeptide 9, and calcyphosin, were further verified by quantitative Western blot analysis of hippocampal tissues from additional normal subjects. Bioinformatic analysis showed that the upregulated and downregulated proteins were largely involved in several important protein-protein interaction networks. Proteins in the electron transport chain and synaptic vesicle fusion pathway were consistently downregulated with aging, whereas proteins associated with Alzheimer's disease showed little change. Our study demonstrates substantial protein profile changes in the human hippocampus during aging, which could be of relevance to age-related loss of hippocampal functions.
authors.affiliation: National Key Laboratory of Medical Molecular Biology & Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Benhong
authors.initials: B
authors.lastname: Xu
authors.affiliation: National Key Laboratory of Medical Molecular Biology & Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Yanpan
authors.initials: Y
authors.lastname: Gao
authors.affiliation: National Key Laboratory of Medical Molecular Biology & Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Shaohua
authors.initials: S
authors.lastname: Zhan
authors.affiliation: National Key Laboratory of Medical Molecular Biology & Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Xiong
authors.affiliation: Department of Human Anatomy, Histology and Embryology, Institute of Basic Medical Sciences, Neuroscience Center, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China.
authors.forename: Wenying
authors.initials: W
authors.lastname: Qiu
authors.affiliation: Department of Human Anatomy, Histology and Embryology, Institute of Basic Medical Sciences, Neuroscience Center, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Qian
authors.affiliation: Department of Human Anatomy, Histology and Embryology, Institute of Basic Medical Sciences, Neuroscience Center, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Human Anatomy, Histology and Embryology, Institute of Basic Medical Sciences, Neuroscience Center, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China.
authors.forename: Naili
authors.initials: N
authors.lastname: Wang
authors.affiliation: Department of Human Anatomy, Histology and Embryology, Institute of Basic Medical Sciences, Neuroscience Center, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China.
authors.forename: Di
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Human Anatomy, Histology and Embryology, Institute of Basic Medical Sciences, Neuroscience Center, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Renzhi
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Xinjie
authors.initials: X
authors.lastname: Bao
authors.affiliation: Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Wanchen
authors.initials: W
authors.lastname: Dou
authors.affiliation: Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Tian
authors.affiliation: National Key Laboratory of Medical Molecular Biology & Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Meng
authors.affiliation: Department of Surgery and Centre for Neuroscience, Flinders University School of Medicine, Bedford Park, SA, Australia.
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Gai
authors.affiliation: School of Medical Sciences, University of New South Wales, Sydney, Australia.
authors.forename: Yue
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Anatomy and Neurobiology, Central South University School of Basic Medical Science, Changsha, Hunan, China.
authors.forename: Xiao-Xin
authors.initials: XX
authors.lastname: Yan
authors.affiliation: National Key Laboratory of Medical Molecular Biology & Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, China. Electronic address: wei.ge@chem.ox.ac.uk.
authors.forename: Wei
authors.initials: W
authors.lastname: Ge
authors.affiliation: Department of Human Anatomy, Histology and Embryology, Institute of Basic Medical Sciences, Neuroscience Center, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China. Electronic address: machao@ibms.cams.cn.
authors.forename: Chao
authors.initials: C
authors.lastname: Ma
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics* / Q000378:metabolism*; D044466:Asian People; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics; D004579:Electron Transport / Q000235:genetics; D005260:Female; D015870:Gene Expression / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics*; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics* / Q000378:metabolism*; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics* / Q000378:metabolism*; D018994:Myosin Light Chains / Q000235:genetics / Q000378:metabolism; D054730:Protein Interaction Domains and Motifs; D013572:Synaptic Vesicles / Q000235:genetics; D053719:Tandem Mass Spectrometry; D015854:Up-Regulation / Q000235:genetics; D014746:Vimentin / Q000235:genetics* / Q000378:metabolism*; D055815:Young Adult
chemical_list: C059605:CAPS protein, human; D002135:Calcium-Binding Proteins; D008840:Microfilament Proteins; D009124:Muscle Proteins; D018994:Myosin Light Chains; D014746:Vimentin; C051615:transgelin
keywords: Alzheimer's disease; Brain aging; Electron transport chain; Proteomics; Synaptic vesicle fusion