Xu Benhong, Gao Yanpan, Zhan Shaohua, Xiong Feng, Qiu Wenying, Qian Xiaojing, Wang Tao, Wang Naili, Zhang Di, Yang Qian, Wang Renzhi, Bao Xinjie, Dou Wanchen, Tian Rui, Meng Shu, Gai Wei-Ping, Huang Yue, Yan Xiao-Xin, Ge Wei, Ma Chao
National Key Laboratory of Medical Molecular Biology & Department of Immunology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, China.
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.
Neurobiol Aging. 2016 Mar;39:46-56. doi: 10.1016/j.neurobiolaging.2015.11.029. Epub 2015 Dec 8.
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.
海马体在人类中似乎普遍受到衰老和各种神经系统疾病的影响，然而，对于这个脑结构中整体蛋白质表达的年龄相关变化却知之甚少。我们使用4重串联质量标签标记法，利用中国受试者的死后大脑，对正常衰老过程中的海马体进行了定量蛋白质组学研究。从16名死于非神经/精神疾病的受试者获取的海马体样本被分为4个年龄组：22 - 49岁、50 - 69岁、70 - 89岁和90岁以上。在分析的4582种蛋白质中，随着年龄增长，有35种蛋白质显著升高，而25种蛋白质下调。包括原肌球蛋白、波形蛋白、肌球蛋白调节轻链多肽9和钙磷蛋白在内的几种上调蛋白质，通过对另外正常受试者海马体组织的定量蛋白质印迹分析得到了进一步验证。生物信息学分析表明，上调和下调的蛋白质主要参与了几个重要的蛋白质 - 蛋白质相互作用网络。电子传递链和突触小泡融合途径中的蛋白质随着衰老持续下调，而与阿尔茨海默病相关的蛋白质变化不大。我们的研究表明，衰老过程中人类海马体的蛋白质谱有显著变化，这可能与海马体功能的年龄相关丧失有关。
