Quantitative protein profiling of hippocampus during human aging

Xu, Benhong; Gao, Yanpan; Zhan, Shaohua; Xiong, Feng; Qiu, Wenying; Qian, Xiaoxian; Wang, Tao; Wang, Nai‐Li; Zhang, Di; Yang, Qian; Wang, Renzhi; Bao, Xinjie; Dou, Wei; Tian, Rui; Meng, Shu; Gai, Wei-Ping; Huang, Yue; Yan, Xiao‐Xin; Ge, Wei; Ma, Chao

doi:10.1016/j.neurobiolaging.2015.11.029

Cited by 60 publications

(46 citation statements)

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“…1A and B, supplementary tables 2 and 3). Our observation of 5.5% of differentially expressed proteins (including trademark aging proteins such as GFAP, CaMKIV, MAPT, CALB1) during aging is in agreement with several MS-based aging studies (Chen et al, 2003; Manavalan et al, 2013; Pan et al, 2007; Xu et al, 2016a; Xu et al, 2016b). However, numerous key differences should be noted in comparison to earlier studies such as: a) investigation of age-related changes in larger cohort of human subjects (33 vs. 4–16; b) less starting material (30–40 mm 2 vs. whole cortex or mg of tissue); c) region and layer specific resolution (OFC layer 2/3 vs. whole cortex and hippocampus); d) male subjects compared to male and female or female subjects alone; and, finally, e) cohesive results highlighting changes in neural communication.…”

Section: Discussionsupporting

confidence: 92%

“…Our results support and provide indirect evidence regarding the age-associated loss at the synaptic level. Alterations in protein levels related to neural communication, although not always cohesive, were also observed in several targeted proteomic studies performed on human postmortem aging tissue (Chen et al, 2003; Manavalan et al, 2013; Pan et al, 2007; Xu et al, 2016a; Xu et al, 2016b). …”

Section: Discussionmentioning

confidence: 69%

“…Most MS-based proteomics studies performed until now on human aging cortical tissue have focused on a limited number of proteins (Chen et al, 2003; Manavalan et al, 2013; Pan et al, 2007; Xu et al, 2016a; Xu et al, 2016b). Here, we performed an exploratory large-scale unbiased (i.e., no a priori selection) proteomic profiling of OFC (areas BA11/47) layer 2/3 in healthy aging subjects compared to a younger cohort.…”

Section: Introductionmentioning

confidence: 99%

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Resilient protein co-expression network in male orbitofrontal cortex layer 2/3 during human aging

Pabba

Scifo

Kapadia

et al. 2017

Neurobiology of Aging

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The orbitofrontal cortex (OFC) is vulnerable to normal and pathological aging. Currently, layer resolution large-scale proteomic studies describing “normal” age-related alterations at OFC are not available. Here, we performed a large-scale exploratory high-throughput mass spectrometry-based protein analysis on OFC layer 2/3 from 15 “young” (15–43 years) and 18 “old” (62–88 years) human male subjects. We detected 4,193 proteins and identified 127 differently expressed proteins (DE) (p-value ≤0.05; effect size >20%), including 65 up- and 62 down-regulated proteins (e.g., GFAP, CALB1). Using a previously-described categorization of biological aging based on somatic tissues, i.e., peripheral “hallmarks of aging”, and considering overlap in protein function, we show highest representation of altered cell-cell communication (54%), deregulated nutrient sensing (39%) and loss of proteostasis (35%) in the set of OFC layer 2/3 DE proteins. DE proteins also showed a significant association with several neurological disorders, e.g., Alzheimer’s disease and schizophrenia. Notably, despite age-related changes in individual protein levels, protein co-expression modules were remarkably conserved across age groups, suggesting robust functional homeostasis. Collectively, these results provide biological insight into aging and associated homeostatic mechanisms that maintain normal brain function with advancing age.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 69%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Resilient protein co-expression network in male orbitofrontal cortex layer 2/3 during human aging

Pabba

Scifo

Kapadia

et al. 2017

Neurobiology of Aging

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“…Proteins were extracted from the right hippocampus of rhesus macaques using of the liquid nitrogen homogenization method [14]. Tissues were homogenized in ice-cold lysis buffer (8 M urea and 1 cocktail in PBS, pH 8.0) and then transferred to a 1.5-mL tube on ice for centrifugation at 12,000 rpm (15 min, 4°C) to remove cellular debris.…”

Section: Sample Preparationmentioning

confidence: 99%

Proteomics profiling and pathway analysis of hippocampal aging in rhesus monkeys

Meng

Xia

Pan

et al. 2019

Preprint

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Background: Aged rhesus monkeys exhibit deficits in memory mediated by the hippocampus. Although extensive research has been carried out on the characteristics of human hippocampal aging, there is still very little scientific understanding of the changes associated with hippocampal aging in rhesus monkeys. To explore the proteomics profiling and pathway-related changes in the rhesus hippocampus during the aging process, we conducted a high throughput quantitative proteomics analysis of hippocampal samples from two groups of rhesus macaques aged 6 years and 20 years, using 2-plex tandem mass tag (TMT) labeling. In addition, we used a comprehensive bioinformatics analysis approach to investigate the enriched signaling pathways of differentially expressed proteins (the ratios of 20-y vs. 6-y, ≥1.20 or ≤ 0.83). Results: In total, 3,260 proteins were identified with a high level of confidence in rhesus hippocampus. We found 367 differentially expressed proteins related to rhesus hippocampus aging. Based on biological pathway analysis, we found these aging-related proteins were predominantly enriched in the electron transport chain, NRF2 pathway, focal adhesion-PI3K-AKT-mTOR signaling pathway and cytoplasmic ribosome proteins. Data are available via ProteomeXchange with identifier PXD011398. Conclusion: This study provides a detail description of the proteomics profile related to rhesus hippocampal aging. These findings should make an important contribution to further mechanistic studies, marker selection and drug development for the prevention and treatment of aging or age-related neurodegeneration.

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“…1 Indeed, high-performance liquid chromatography separation showed that Protein S100-A9, Neuropilin-1, CRMP1, Myelin protein P2, Tubulin polymerization-promoting protein, Isoform-2 of Vitamin D-binding protein, Neuron-specific calcium binding protein, and Rab-3D (which is critical in neuritic plasticity) are decreased in aged post-mortem human hippocampus. 2 By contrast, the vast majority of proteins -more than 4000 quantified proteinsfrom aged frontal cortex/hippocampus of mouse remain unchanged. 3 Since the aged hippocampus (dys)function is consistently associated to functional connectivity, network dynamic, and electrophysiological parameters (Ca ++ /Na + /K + regulation, LTP, potentiation of synaptic activation) mediated by the release of numerous neuromediators (such as acetylcholine, dopamine, norepinephrine, serotonin, GABA, glycine and glutamic acid), it is appealing to review the implication of gene expression underlying the aged-related change within these anatomical sites.…”

Section: Introductionmentioning

confidence: 99%