Immunity & AgeingPub Date : 2024-01-02DOI: 10.1186/s12979-023-00402-3
Cristina Rodriguez-Rodriguez, Natalia González-Mancha, Ane Ochoa-Echeverría, Rosa Liébana, Isabel Merida
{"title":"Partial loss of Sorting Nexin 27 resembles age- and Down syndrome-associated T cell dysfunctions","authors":"Cristina Rodriguez-Rodriguez, Natalia González-Mancha, Ane Ochoa-Echeverría, Rosa Liébana, Isabel Merida","doi":"10.1186/s12979-023-00402-3","DOIUrl":"https://doi.org/10.1186/s12979-023-00402-3","url":null,"abstract":"Sorting Nexin 27 (SNX27)-retromer complex facilitates cargo recycling from endosomes to the plasma membrane. SNX27 downregulation in neurons, as the result of Trisomy 21 (T21), has been linked with cognitive deficits due to impairment of AMPA and NMDA receptor recycling. Studies in human T cell lines likewise demonstrated that SNX27 regulates the correct delivery of cargoes to the immune synapse limiting the activation of pro-inflammatory pathways. Nevertheless, the physiological consequences of partial SNX27 loss in T cell homeostasis are still unclear. In this study, we have explored the consequences of T cell specific partial SNX27 downregulation in mice. T cells with partial SNX27 deficiency show a marked deficit in the CD4+ T cell pool, a hallmark of aging in mice and humans, and a well-characterized comorbidity of individuals with Down syndrome (DS). When analyzed ex vivo, CD4+ T cells with partial SNX27 deletion demonstrate enhanced proliferation but diminished IL-2 production. In contrast, the CD8+ population show enhanced expression of pro-inflammatory cytokines and lytic enzymes. This mouse model supports the relevance of SNX27 in the organization of the immune synapse, previously described in cell lines, as well as in the control of T cell homeostasis. Individuals with DS experiment an acceleration of the aging process, which particularly affects the immune and central nervous systems. Thus, we hypothesize that reduced SNX27 expression in DS could contribute to the dysregulation of these systems and further research in SNX27 will shed light on the molecular factors underlying the phenotypes observed in people with DS and its contribution to aging.","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":"40 1","pages":""},"PeriodicalIF":7.9,"publicationDate":"2024-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139078394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"An aging-related immune landscape in the hematopoietic immune system","authors":"Jianjie Lv, Chun Zhang, Xiuxing Liu, Chenyang Gu, Yidan Liu, Yuehan Gao, Zhaohao Huang, Qi Jiang, Binyao Chen, Daquan He, Tianfu Wang, Zhuping Xu, Wenru Su","doi":"10.1186/s12979-023-00403-2","DOIUrl":"https://doi.org/10.1186/s12979-023-00403-2","url":null,"abstract":"Aging is a holistic change that has a major impact on the immune system, and immunosenescence contributes to the overall progression of aging. The bone marrow is the most important hematopoietic immune organ, while the spleen, as the most important extramedullary hematopoietic immune organ, maintains homeostasis of the human hematopoietic immune system (HIS) in cooperation with the bone marrow. However, the overall changes in the HIS during aging have not been described. Here, we describe a hematopoietic immune map of the spleen and bone marrow of young and old mice using single-cell sequencing and flow cytometry techniques. We observed extensive, complex changes in the HIS during aging. Compared with young mice, the immune cells of aged mice showed a marked tendency toward myeloid differentiation, with the neutrophil population accounting for a significant proportion of this response. In this change, hypoxia-inducible factor 1-alpha (Hif1α) was significantly overexpressed, and this enhanced the immune efficacy and inflammatory response of neutrophils. Our research revealed that during the aging process, hematopoietic stem cells undergo significant changes in function and composition, and their polymorphism and differentiation abilities are downregulated. Moreover, we found that the highly responsive CD62L + HSCs were obviously downregulated in aging, suggesting that they may play an important role in the aging process. Overall, aging extensively alters the cellular composition and function of the HIS. These findings could potentially give high-dimensional insights and enable more accurate functional and developmental analyses as well as immune monitoring in HIS aging.","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":"26 1","pages":""},"PeriodicalIF":7.9,"publicationDate":"2024-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139078397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Immunity & AgeingPub Date : 2023-12-18DOI: 10.1186/s12979-023-00401-4
Robertina Giacconi, Patrizia D’Aquila, Maurizio Cardelli, Francesco Piacenza, Elisa Pierpaoli, Giada Sena, Mirko Di Rosa, Anna Rita Bonfigli, Roberta Galeazzi, Antonio Cherubini, Massimiliano Fedecostante, Riccardo Sarzani, Chiara Di Pentima, Piero Giordano, Roberto Antonicelli, Fabrizia Lattanzio, Giuseppe Passarino, Mauro Provinciali, Dina Bellizzi
{"title":"Blood circulating bacterial DNA in hospitalized old COVID-19 patients","authors":"Robertina Giacconi, Patrizia D’Aquila, Maurizio Cardelli, Francesco Piacenza, Elisa Pierpaoli, Giada Sena, Mirko Di Rosa, Anna Rita Bonfigli, Roberta Galeazzi, Antonio Cherubini, Massimiliano Fedecostante, Riccardo Sarzani, Chiara Di Pentima, Piero Giordano, Roberto Antonicelli, Fabrizia Lattanzio, Giuseppe Passarino, Mauro Provinciali, Dina Bellizzi","doi":"10.1186/s12979-023-00401-4","DOIUrl":"https://doi.org/10.1186/s12979-023-00401-4","url":null,"abstract":"Coronavirus disease COVID-19 is a heterogeneous condition caused by SARS-CoV-2 infection. Generally, it is characterized by interstitial pneumonia that can lead to impaired gas-exchange, acute respiratory failure, and death, although a complex disorder of multi-organ dysfunction has also been described. The pathogenesis is complex, and a variable combination of factors has been described in critically ill patients. COVID-19 is a particular risk for older persons, particularly those with frailty and comorbidities. Blood bacterial DNA has been reported in both physiological and pathological conditions and has been associated with some haematological and laboratory parameters but, to date, no study has characterized it in hospitalized old COVID-19 patients The present study aimed to establish an association between blood bacterial DNA (BB-DNA) and clinical severity in old COVID-19 patients. BB-DNA levels were determined, by quantitative real-time PCRs targeting the 16S rRNA gene, in 149 hospitalized older patients (age range 65–99 years) with COVID-19. Clinical data, including symptoms and signs of infection, frailty status, and comorbidities, were assessed. BB-DNA was increased in deceased patients compared to discharged ones, and Cox regression analysis confirmed an association between BB-DNA and in-hospital mortality. Furthermore, BB-DNA was positively associated with the neutrophil count and negatively associated with plasma IFN-alpha. Additionally, BB-DNA was associated with diabetes. The association of BB-DNA with mortality, immune-inflammatory parameters and diabetes in hospitalized COVID-19 patients suggests its potential role as a biomarker of unfavourable outcomes of the disease, thus it could be proposed as a novel prognostic marker in the assessment of acute COVID-19 disease.","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":"93 1","pages":""},"PeriodicalIF":7.9,"publicationDate":"2023-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138716098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The inter-link of ageing, cancer and immunity: findings from real-world retrospective study","authors":"Xiaomin Fu, Peng Qin, Fanghui Li, Huifang Zhu, Hongqin You, Yong Zhang, Benling Xu, Tiepeng Li, Fang Zhang, Lu Han, Lingdi Zhao, Baozhen Ma, Zibing Wang, Quanli Gao","doi":"10.1186/s12979-023-00399-9","DOIUrl":"https://doi.org/10.1186/s12979-023-00399-9","url":null,"abstract":"Although the concept of declined immune function associated with cancer has been accepted extensively, real-world clinical studies focusing on analysis of the peripheral blood immune changes underlying ageing, immunity and cancer are scarce. In this case-control study, we retrospectively analysed 1375 cancer patients and enrolled 275 age and gender matched healthy individuals. Flow cytometry was conducted to assess the immune changes. Further analysis was examined by SPSS 17.0 and GraphPad Prism 9 software. Cancer patients showed obviously decreased CD3+ T, CD3+CD4+ Th, CD3+CD8+ CTL, CD19+ B, CD16+CD56+ NK cell counts and lower percentage of PD-1 (programmed cell death protein-1, PD-1) positive cells than healthy control (P < 0.0001). For cancer patients, the reference range of circulating percentage of PD-1+CD45+ cells, PD-1+CD3+ T cells, PD-1+CD3+CD4+ Th cells and PD-1+CD3+CD8+ CTL (Cytotoxic T Lymphocyte, CTL) were 11.2% (95% CI 10.8%-11.6%), 15.5% (95% CI 14.7%-16.0%), 15.4% (95% CI 14.9%-16.0%) and 14.5% (95% CI 14.0%-15.5%), respectively. Moreover, the reduction of CD3+ T, CD3+CD4+ Th, CD3+CD8+ CTL, CD19+ B cell counts accompanied with age and stage advancing (P < 0.05). CD16+CD56+ NK cells decreased with stage, but elevated in aged and male cancer patients (P < 0.05). Additionally, the percentage of PD-1 positive cells varied across cancer types, raised with age and stage. Head and neck, pancreatic, gynaecological and lung demonstrated a higher level of the percentage of PD-1 positive cells than melanoma, prostate, and breast cancer (P < 0.05). This study provides the reference range of the percentage of PD-1 positive cells on peripheral blood, confirms the decreased immune cells and a series of immune changes accompanying with cancer, expands our real world evidence to better understand the interactions of ageing, cancer and immunity. Moreover, the circulating percentage of PD-1 positive cells shows similar tumor type distribution with tumor mutational burden (TMB), supports that it maybe a potential predictive biomarker for immune checkpoint inhibitor therapy.","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":"24 1","pages":""},"PeriodicalIF":7.9,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138683521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Immunity & AgeingPub Date : 2023-12-14DOI: 10.1186/s12979-023-00397-x
Min Cao, Jing Liu, Xiaomin Zhang, Yaqi Wang, Yuli Hou, Qiao Song, Yuting Cui, Yue Zhao, Peichang Wang
{"title":"IL-17A promotes the progression of Alzheimer’s disease in APP/PS1 mice","authors":"Min Cao, Jing Liu, Xiaomin Zhang, Yaqi Wang, Yuli Hou, Qiao Song, Yuting Cui, Yue Zhao, Peichang Wang","doi":"10.1186/s12979-023-00397-x","DOIUrl":"https://doi.org/10.1186/s12979-023-00397-x","url":null,"abstract":"Alzheimer’s disease (AD), which is the most common cause of dementia in elderly individuals, is a progressive neurodegenerative disorder. Neuroinflammation, which is an immune response that is activated by glial cells in the central nervous system, plays an important role in neurodegenerative diseases. Many studies have shown that interleukin-17A (IL-17A) plays an important role in AD, but research on the pathological effects of IL-17A on AD is limited. We report the effect of IL-17A on AD progression in APPswe/PS1dE9 (APP/PS1) mice, which are the most widely used AD model mice. The BV2 cell line, which is a microglial cell line derived from C57/BL6 mice, was used to establish a cell model to verify the role of IL-17A in neuroinflammation at the cellular level. The HT22 hippocampal neuronal cell line was used to investigate the relationship between IL-17A and Aβ deposition. In this research, we found that IL-17A promotes the progression of AD in the APP/PS1 mouse model. The role of IL-17A in neuroinflammation is related to tumour necrosis factor (TNF)-α. Circulating IL-17A stimulates the secretion of TNF-α by microglia through the Toll-like receptor 4 (TLR4)/nuclear factor (NF)-κB signalling pathway, thus exacerbating neuroinflammation. In addition, intraperitoneal injection of IL-17A antibody (IL17Ab) significantly improved the cognitive function of APP/PS1 mice. IL-17A increased TNF-α levels in the brain and exacerbated neuroinflammation through the TLR4/NF-κB signalling pathway and microglial activation in APP/PS1 mice. Moreover, IL-17A promoted the progression of AD by enhancing neuroinflammation, inhibiting microglial phagocytosis, and promoting the deposition of β-amyloid 42 in AD model mice.","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":"6 4 1","pages":""},"PeriodicalIF":7.9,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138629061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Immunity & AgeingPub Date : 2023-12-12DOI: 10.1186/s12979-023-00394-0
Jia Yang, Hai-Cheng Liu, Jian-Qing Zhang, Jian-Yong Zou, Xin Zhang, Wo-Ming Chen, Yong Gu, Hai Hong
{"title":"The effect of metformin on senescence of T lymphocytes","authors":"Jia Yang, Hai-Cheng Liu, Jian-Qing Zhang, Jian-Yong Zou, Xin Zhang, Wo-Ming Chen, Yong Gu, Hai Hong","doi":"10.1186/s12979-023-00394-0","DOIUrl":"https://doi.org/10.1186/s12979-023-00394-0","url":null,"abstract":"Immunosenescence occurs as people age, leading to an increased incidence of age-related diseases. The number of senescent T cells also rises with age. T cell senescence and immune response dysfunction can result in a decline in immune function, especially in anti-tumor immune responses. Metformin has been shown to have various beneficial effects on health, such as lowering blood sugar levels, reducing the risk of cancer development, and slowing down the aging process. However, the immunomodulatory effects of metformin on senescent T cells still need to be investigated. PBMCs isolation from different age population (n = 88); Flow Cytometry is applied to determine the phenotypic characterization of senescent T lymphocytes; intracellular staining is applied to determine the function of senescent T cells; Enzyme-Linked Immunosorbent Assay (ELISA) is employed to test the telomerase concentration. The RNA-seq analysis of gene expression associated with T cell senescence. The middle-aged group had the highest proportion of senescent T cells. We found that metformin could decrease the number of CD8 + senescent T cells. Metformin affects the secretion of SASP, inhibiting the secretion of IFN-γ in CD8 + senescent T cells. Furthermore, metformin treatment restrained the production of the proinflammatory cytokine IL-6 in lymphocytes. Metformin had minimal effects on Granzyme B secretion in senescent T cells, but it promoted the production of TNF-α in senescent T cells. Additionally, metformin increased the concentration of telomerase and the frequency of undifferentiated T cells. The results of RNA-seq showed that metformin promoted the expression of genes related to stemness and telomerase activity, while inhibiting the expression of DNA damage-associated genes. Our findings reveal that metformin could inhibit T cell senescence in terms of cell number, effector function, telomerase content and gene expression in middle-aged individuals, which may serve as a promising approach for preventing age-related diseases in this population.","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":"69 1","pages":""},"PeriodicalIF":7.9,"publicationDate":"2023-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138576617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Senescence-associated secretory phenotypes in mesenchymal cells contribute to cytotoxic immune response in oral lichen planus.","authors":"Shogo Ijima, Yuki Saito, Sena Yamamoto, Kentaro Nagaoka, Taiki Iwamoto, Arisa Kita, Maki Miyajima, Tsukasa Sato, Akihiro Miyazaki, Takako S Chikenji","doi":"10.1186/s12979-023-00400-5","DOIUrl":"10.1186/s12979-023-00400-5","url":null,"abstract":"<p><p>Oral lichen planus is a chronic inflammatory condition that adversely affects the oral mucosa; however, its etiology remains elusive. Consequently, therapeutic interventions for oral lichen planus are limited to symptomatic management. This study provides evidence of the accumulation of senescent mesenchymal cells, CD8 + T cells, and natural killer cells in patients with oral lichen planus. We profiled the patients' tissues using the National Center for Biotechnology Information Gene Expression Omnibus database and found that senescence-related genes were upregulated in these tissues by gene set enrichment analysis. Immunohistochemical analysis showed increased senescent mesenchymal cells in the subepithelial layer of patients with oral lichen planus. Single-cell RNA-seq data retrieved from the Gene Expression Omnibus database of patients with oral lichen planus revealed that mesenchymal cells were marked by the upregulation of senescence-related genes. Cell-cell communication analysis using CellChat showed that senescent mesenchymal cells significantly influenced CD8 + T cells and natural killer cells via CXCL12-CXCR4 signaling, which is known to activate and recruit CD8 + T cells and NK cells. Finally, in vitro assays demonstrated that the secretion of senescence-associated factors from mesenchymal cells stimulated the activation of T cells and natural killer cells and promoted epithelial cell senescence and cytotoxicity. These findings suggest that the accumulation of mesenchymal cells with senescence-associated secretory phenotype may be a key driver of oral lichen planus pathogenesis.</p>","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":"20 1","pages":"72"},"PeriodicalIF":7.9,"publicationDate":"2023-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10696703/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138489019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Impact of NAD+ metabolism on ovarian aging.","authors":"Jinghui Liang, Feiling Huang, Zhaoqi Song, Ruiyi Tang, Peng Zhang, Rong Chen","doi":"10.1186/s12979-023-00398-w","DOIUrl":"10.1186/s12979-023-00398-w","url":null,"abstract":"<p><p>Nicotinamide adenine dinucleotide (NAD+), a crucial coenzyme in cellular redox reactions, is closely associated with age-related functional degeneration and metabolic diseases. NAD exerts direct and indirect influences on many crucial cellular functions, including metabolic pathways, DNA repair, chromatin remodeling, cellular senescence, and immune cell functionality. These cellular processes and functions are essential for maintaining tissue and metabolic homeostasis, as well as healthy aging. Causality has been elucidated between a decline in NAD levels and multiple age-related diseases, which has been confirmed by various strategies aimed at increasing NAD levels in the preclinical setting. Ovarian aging is recognized as a natural process characterized by a decline in follicle number and function, resulting in decreased estrogen production and menopause. In this regard, it is necessary to address the many factors involved in this complicated procedure, which could improve fertility in women of advanced maternal age. Concerning the decrease in NAD+ levels as ovarian aging progresses, promising and exciting results are presented for strategies using NAD+ precursors to promote NAD+ biosynthesis, which could substantially improve oocyte quality and alleviate ovarian aging. Hence, to acquire further insights into NAD+ metabolism and biology, this review aims to probe the factors affecting ovarian aging, the characteristics of NAD+ precursors, and the current research status of NAD+ supplementation in ovarian aging. Specifically, by gaining a comprehensive understanding of these aspects, we are optimistic about the prominent progress that will be made in both research and therapy related to ovarian aging.</p>","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":"20 1","pages":"70"},"PeriodicalIF":7.9,"publicationDate":"2023-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10693113/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138471155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Immunity & AgeingPub Date : 2023-12-02DOI: 10.1186/s12979-023-00396-y
Juan Joseph Young, Hong-Jai Park, Minhyung Kim, Jennefer Par-Young, Hugh Bartlett, Hye Sun Kim, Serhan Unlu, Lais Osmani, Min Sun Shin, Richard Bucala, Christopher H van Dyck, Heather Allore, Adam P Mecca, Sungyong You, Insoo Kang
{"title":"Aging gene signature of memory CD8<sup>+</sup> T cells is associated with neurocognitive functioning in Alzheimer's disease.","authors":"Juan Joseph Young, Hong-Jai Park, Minhyung Kim, Jennefer Par-Young, Hugh Bartlett, Hye Sun Kim, Serhan Unlu, Lais Osmani, Min Sun Shin, Richard Bucala, Christopher H van Dyck, Heather Allore, Adam P Mecca, Sungyong You, Insoo Kang","doi":"10.1186/s12979-023-00396-y","DOIUrl":"10.1186/s12979-023-00396-y","url":null,"abstract":"<p><strong>Background: </strong>Memory CD8<sup>+</sup> T cells expand with age. We previously demonstrated an age-associated expansion of effector memory (EM) CD8<sup>+</sup> T cells expressing low levels of IL-7 receptor alpha (IL-7Rα<sup>low</sup>) and the presence of its gene signature (i.e., IL-7Rα<sup>low</sup> aging genes) in peripheral blood of older adults without Alzheimer's disease (AD). Considering age as the strongest risk factor for AD and the recent finding of EM CD8<sup>+</sup> T cell expansion, mostly IL-7Rα<sup>low</sup> cells, in AD, we investigated whether subjects with AD have alterations in IL-7Rα<sup>low</sup> aging gene signature, especially in relation to genes possibly associated with AD and disease severity.</p><p><strong>Results: </strong>We identified a set of 29 candidate genes (i.e., putative AD genes) which could be differentially expressed in peripheral blood of patients with AD through the systematic search of publicly available datasets. Of the 29 putative AD genes, 9 genes (31%) were IL-7Rα<sup>low</sup> aging genes (P < 0.001), suggesting the possible implication of IL-7Rα<sup>low</sup> aging genes in AD. These findings were validated by RT-qPCR analysis of 40 genes, including 29 putative AD genes, additional 9 top IL-7R⍺<sup>low</sup> aging but not the putative AD genes, and 2 inflammatory control genes in peripheral blood of cognitively normal persons (CN, 38 subjects) and patients with AD (40 mild cognitive impairment and 43 dementia subjects). The RT-qPCR results showed 8 differentially expressed genes between AD and CN groups; five (62.5%) of which were top IL-7Rα<sup>low</sup> aging genes (FGFBP2, GZMH, NUAK1, PRSS23, TGFBR3) not previously reported to be altered in AD. Unbiased clustering analysis revealed 3 clusters of dementia patients with distinct expression levels of the 40 analyzed genes, including IL-7Rα<sup>low</sup> aging genes, which were associated with neurocognitive function as determined by MoCA, CDRsob and neuropsychological testing.</p><p><strong>Conclusions: </strong>We report differential expression of \"normal\" aging genes associated with IL-7Rα<sup>low</sup> EM CD8<sup>+</sup> T cells in peripheral blood of patients with AD, and the significance of such gene expression in clustering subjects with dementia due to AD into groups with different levels of cognitive functioning. These results provide a platform for studies investigating the possible implications of age-related immune changes, including those associated with CD8<sup>+</sup> T cells, in AD.</p>","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":"20 1","pages":"71"},"PeriodicalIF":7.9,"publicationDate":"2023-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10693128/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138479252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Immunity & AgeingPub Date : 2023-11-29DOI: 10.1186/s12979-023-00392-2
Sean X Leng, Albert C Shaw
{"title":"Fundamental and frontier research of immune responses to influenza vaccines in human aging: from cross-sectional and longitudinal studies to clinical trials and the geroscience perspective.","authors":"Sean X Leng, Albert C Shaw","doi":"10.1186/s12979-023-00392-2","DOIUrl":"10.1186/s12979-023-00392-2","url":null,"abstract":"","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":"20 1","pages":"69"},"PeriodicalIF":7.9,"publicationDate":"2023-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10685665/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138464265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}