Immunity & Ageing最新文献

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Micro nutrients as immunomodulators in the ageing population: a focus on inflammation and autoimmunity. 微量营养素作为老龄化人口的免疫调节剂:关注炎症和自身免疫。
IF 5.2 2区 医学
Immunity & Ageing Pub Date : 2024-12-27 DOI: 10.1186/s12979-024-00492-7
Bhavani Sowndharya Balamurugan, Mathan Muthu Chinnakannu Marimuthu, Vickram Agaram Sundaram, Bharath Saravanan, Prasanth Chandrababu, Hitesh Chopra, Tabarak Malik
{"title":"Micro nutrients as immunomodulators in the ageing population: a focus on inflammation and autoimmunity.","authors":"Bhavani Sowndharya Balamurugan, Mathan Muthu Chinnakannu Marimuthu, Vickram Agaram Sundaram, Bharath Saravanan, Prasanth Chandrababu, Hitesh Chopra, Tabarak Malik","doi":"10.1186/s12979-024-00492-7","DOIUrl":"10.1186/s12979-024-00492-7","url":null,"abstract":"<p><p>Immunosenescence, the slow degradation of immune function over time that is a hallmark and driver of aging, makes older people much more likely to be killed by common infections (such as flu) than young adults, but it also contributes greatly to rates of chronic inflammation in later life. Such micro nutrients are crucial for modulating effective immune responses and their deficiencies have been associated with dysfunctional immunity in the elderly. In this review, we specifically focused on the contribution of major micro nutrients (Vitamins A, D and E, Vitamin C; Zinc and Selenium) as immunomodulators in ageing population especially related to inflame-ageing process including autoimmunity. This review will cover these hologenomic interactions, including how micro nutrients can modulate immune cell function and/or cytokine production to benefit their hosts with healthy mucous-associated immunity along with a sustainable immunologic homeostasis. For example, it points out the modulatory effects of vitamin D on both innate and adaptive immunity, with a specific focus on its ability to suppress pro-inflammatory cytokines synthesis while enhancing regulatory T-cell function. In the same context, also zinc is described as important nutrient for thymic function and T-cell differentiation but exhibits immunomodulatory functions by decreasing inflammation. In addition, the review will go over how micro nutrient deficiencies increase systemic chronic low-grade inflammation and, inflammaging as well as actually enhance autoimmune pathologies in old age. It assesses the potential role of additional targeted nutritional supplementation with micro nutrients to counteract these effects, promoting wider immune resilience in older adults. This review collates the current evidence and highlights the role of adequate micro nutrient intake on inflammation and autoimmunity during ageing, providing plausible origins for nutritional interventions to promote healthy immune aging.</p>","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":"21 1","pages":"88"},"PeriodicalIF":5.2,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11674512/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900327","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}
引用次数: 0
Differential associations of anti-cytomegalovirus antibodies and soluble CD14 levels with immunosenescence in people living with HIV on long term antiretroviral therapy. 抗巨细胞病毒抗体和可溶性CD14水平与长期抗逆转录病毒治疗的HIV感染者免疫衰老的差异关联
IF 5.2 2区 医学
Immunity & Ageing Pub Date : 2024-12-21 DOI: 10.1186/s12979-024-00491-8
Ashwini Vinod Shete, Pallavi Shidhaye, Amrita Rao, Nikita Bhawari, Supriya Deshpande, Jyoti Sawant, Rajani Bagul, Ujjwala Ghule, Sunita Kumbhar, Manisha Ghate
{"title":"Differential associations of anti-cytomegalovirus antibodies and soluble CD14 levels with immunosenescence in people living with HIV on long term antiretroviral therapy.","authors":"Ashwini Vinod Shete, Pallavi Shidhaye, Amrita Rao, Nikita Bhawari, Supriya Deshpande, Jyoti Sawant, Rajani Bagul, Ujjwala Ghule, Sunita Kumbhar, Manisha Ghate","doi":"10.1186/s12979-024-00491-8","DOIUrl":"10.1186/s12979-024-00491-8","url":null,"abstract":"<p><strong>Background: </strong>People living with HIV (PLHIV) demonstrate accelerated aging and immunosenescence in spite of immune-restoration following long-term antiretroviral treatment (ART). Low level inflammation leading to inflammaging plays an important role in mediating premature immunosenescence. Ongoing viral replication, antiretrovirals and subclinical infections with the common viruses like Cytomegalovirus (CMV) are known to induce inflammaging. However such data is scarce in India where persistent low level inflammation is common in general population due to various subclinical infections. Hence we conducted a study to determine the extent of immunosenescence in asymptomatic PLHIV on long term ART in comparison with their age-matched controls.</p><p><strong>Results: </strong>The study was conducted in asymptomatic virally suppressed PLHIV on ART for more than 5 years [n = 70, M: F = 36:34] and HIV uninfected controls [n = 68, M: F = 31:37] belonging to the age-group of 40-55 years. Blood samples were collected for assessing levels of immunosenescence markers on CD4 T cells by flow cytometry and anti-CMV antibodies as well as soluble CD14 (sCD14) levels by ELISA. The levels were compared between cases and controls and correlated with the levels of anti-CMV antibody and sCD14. PLHIV had significantly lower levels of naïve T cells and higher levels of activated and immunosenescent T cells than controls as indicated by CD38, CD57, CD28 expressing CD4 and CD8 T cells. PLHIV had higher levels of anti-CMV antibodies, but lower levels of sCD14 levels and HLADR + CD8 T cells than those in controls. Immunosenescent T cells correlated positively with anti-CMV antibody levels and negatively with sCD14 levels. Duration of dolutegravir based therapy correlated negatively with sCD14 levels.</p><p><strong>Conclusions: </strong>Thus, higher levels of immune activation and immunosenescence in the cases possibly indicate their compromised immune status predisposing PLHIV to infections and cancers. The study indicated a need for CMV treatment regimens even in asymptomatic individuals for preventing immunosenescence. The study also indicated a role of dolutegravir induced loss of sCD14 levels in predisposing PLHIV to immunosenescence.</p>","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":"21 1","pages":"87"},"PeriodicalIF":5.2,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11662588/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142873518","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}
引用次数: 0
Characterisation of specific responses to three models of viral antigens in immunocompetent older adults. 免疫功能正常的老年人对三种病毒抗原模型的特异性反应的特征。
IF 5.2 2区 医学
Immunity & Ageing Pub Date : 2024-12-05 DOI: 10.1186/s12979-024-00488-3
Beatriz Rioseras, Eva Bueno-García, Alejandra García-Torre, Rocío López-Martínez, Marco Antonio Moro-García, Sara Alonso-Álvarez, Victoria Menéndez-García, Alba Lluna-González, Alejandra Sousa-Fernández, Marta Fernández-Gudin, Laura Campos-Riopedre, Corina Castro-Del Cueto, Ana Belén Pérez-Fernández, Ana Alonso-Rodríguez, Carla Menéndez-Peña, Lara Menéndez-Peña, Noelia García-Arnaldo, Estefanía Feito-Díaz, Adriana Fernández-Lorences, Agustín Fraile-Manzano, Carolina Fernández-Iglesias, Jose Arturo Rivera, Carmen Pérez-Fonseca, Estíbaliz Urdiales-Ruano, María Debán-Fernández, Hugo Mendes-Moreira, Pablo Herrero-Puente, Rebeca Alonso-Arias
{"title":"Characterisation of specific responses to three models of viral antigens in immunocompetent older adults.","authors":"Beatriz Rioseras, Eva Bueno-García, Alejandra García-Torre, Rocío López-Martínez, Marco Antonio Moro-García, Sara Alonso-Álvarez, Victoria Menéndez-García, Alba Lluna-González, Alejandra Sousa-Fernández, Marta Fernández-Gudin, Laura Campos-Riopedre, Corina Castro-Del Cueto, Ana Belén Pérez-Fernández, Ana Alonso-Rodríguez, Carla Menéndez-Peña, Lara Menéndez-Peña, Noelia García-Arnaldo, Estefanía Feito-Díaz, Adriana Fernández-Lorences, Agustín Fraile-Manzano, Carolina Fernández-Iglesias, Jose Arturo Rivera, Carmen Pérez-Fonseca, Estíbaliz Urdiales-Ruano, María Debán-Fernández, Hugo Mendes-Moreira, Pablo Herrero-Puente, Rebeca Alonso-Arias","doi":"10.1186/s12979-024-00488-3","DOIUrl":"10.1186/s12979-024-00488-3","url":null,"abstract":"<p><strong>Background: </strong>Memory responses to the antigens that an individual encounters throughout life may vary with the intensity and duration of antigen contacts or even with changes in immune status over time. This work aims to characterise specific responses to latent CMV, seasonal influenza and novel SARS-CoV-2 infections in immunocompetent individuals over 60 years of age. Specific cellular and humoral responses were identified by IFN-γ and granzyme B release by ELISpot and antibody level measurement. T lymphocyte subpopulation phenotypes were characterised by flow cytometry.</p><p><strong>Results: </strong>Cellular and humoral responses to these viruses were detected in almost all patients. Influenza and SARS-CoV-2 cellular responses were positively correlated. There was no significant correlation between CMV and influenza or SARS-CoV-2 responses although both were consistently lower in CMV-seropositive patients. CMV responses were negatively correlated with the levels of the least differentiated subsets of T lymphocytes, and positively correlated with the most differentiated ones, contrary to what happened with the influenza responses. Nevertheless, SARS-CoV-2 cellular responses were negatively correlated with the most differentiated CD8<sup>+</sup> T lymphocytes, while humoral responses were negatively correlated with the least differentiated T lymphocytes. Responses to the three viruses were correlated with a Th1/Th2/Th17 balance in favour of Th1.</p><p><strong>Conclusions: </strong>The results indicate that memory responses differ depending on the durability of the antigen stimulus. Cellular responses to novel pathogens resemble those generated by seasonal but not CMV infection. Subpopulation distribution and the level of specific T lymphocytes against previous pathogens could be used as immunocompetent status biomarkers in older adults reflecting their ability to generate memory responses to new pathogens.</p>","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":"21 1","pages":"86"},"PeriodicalIF":5.2,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11619616/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142787531","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}
引用次数: 0
The role of autoantibodies in bridging obesity, aging, and immunosenescence. 自身抗体在桥接肥胖、衰老和免疫衰老中的作用。
IF 5.2 2区 医学
Immunity & Ageing Pub Date : 2024-11-30 DOI: 10.1186/s12979-024-00489-2
Taylor R Valentino, Nan Chen, Priya Makhijani, Saad Khan, Shawn Winer, Xavier S Revelo, Daniel A Winer
{"title":"The role of autoantibodies in bridging obesity, aging, and immunosenescence.","authors":"Taylor R Valentino, Nan Chen, Priya Makhijani, Saad Khan, Shawn Winer, Xavier S Revelo, Daniel A Winer","doi":"10.1186/s12979-024-00489-2","DOIUrl":"https://doi.org/10.1186/s12979-024-00489-2","url":null,"abstract":"<p><p>Antibodies are essential to immune homeostasis due to their roles in neutralizing pathogenic agents. However, failures in central and peripheral checkpoints that eliminate autoreactive B cells can undermine self-tolerance and generate autoantibodies that mistakenly target self-antigens, leading to inflammation and autoimmune diseases. While autoantibodies are well-studied in autoimmune and in some communicable diseases, their roles in chronic conditions, such as obesity and aging, are less understood. Obesity and aging share similar aspects of immune dysfunction, such as diminished humoral responses and heightened chronic inflammation, which can disrupt immune tolerance and foster autoantigen production, thus giving rise to autoreactive B cells and autoantibodies. In return, these events may also contribute to the pathophysiology of obesity and aging, to the associated autoimmune disorders linked to these conditions, and to the development of immunosenescence, an age-related decline in immune function that heightens vulnerability to infections, chronic diseases, and loss of self-tolerance. Furthermore, the cumulative exposure to antigens and cellular debris during obesity and aging perpetuates pro-inflammatory pathways, linking immunosenescence with other aging hallmarks, such as proteostasis loss and mitochondrial dysfunction. This review examines the mechanisms driving autoantibody generation during obesity and aging and discusses key putative antigenic targets across these conditions. We also explore the therapeutic potential of emerging approaches, such as CAR-T/CAAR-T therapies, vaccines, and BiTEs, to tackle autoimmune-related conditions in aging and obesity.</p>","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":"21 1","pages":"85"},"PeriodicalIF":5.2,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11607830/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142774310","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}
引用次数: 0
Detection of HHV-5 HHV-6a HHV-6b and HHV-7 in the urine: potential use as a non-invasive diagnostic tool for immune profiling. 尿液中HHV-5、HHV-6a、HHV-6b和HHV-7的检测:作为免疫谱分析的非侵入性诊断工具的潜在用途
IF 5.2 2区 医学
Immunity & Ageing Pub Date : 2024-11-29 DOI: 10.1186/s12979-024-00490-9
Shelia Govind, Pierre Olivier Lang, Alexander Bürkle, María Moreno-Villanueva, Claudio Franceschi, Miriam Capri, Jurgen Bernard, Birgit Weinberger, Beatrix Grubeck-Loebenstein, Simone Fiegl, Efstathios S Gonos, Ewa Sikora, Eugène Jansen, Martijn E T Dollé, Tilman Grune, Nicolle Breusing, Richard Aspinall
{"title":"Detection of HHV-5 HHV-6a HHV-6b and HHV-7 in the urine: potential use as a non-invasive diagnostic tool for immune profiling.","authors":"Shelia Govind, Pierre Olivier Lang, Alexander Bürkle, María Moreno-Villanueva, Claudio Franceschi, Miriam Capri, Jurgen Bernard, Birgit Weinberger, Beatrix Grubeck-Loebenstein, Simone Fiegl, Efstathios S Gonos, Ewa Sikora, Eugène Jansen, Martijn E T Dollé, Tilman Grune, Nicolle Breusing, Richard Aspinall","doi":"10.1186/s12979-024-00490-9","DOIUrl":"10.1186/s12979-024-00490-9","url":null,"abstract":"<p><p>Decline in immune function with age has been studied extensively, but approaches to immune restoration have been hampered by the lack of simple methods of identifying individuals whose immune system is in decline. Our approach has been to identify individuals whose immune decline has led to a loss of control of common latent viral infections and their consequent reactivation. Viruses excreted in urine were detected and quantified and we believe this approach could provide a 'surrogate marker' for identifying immune compromised individuals. Here we report the detection of human herpes virus (HHV) 5, 6a, 6b and 7 in the urine of healthy individuals over a wide age range and their correlation with T cell receptor excision circle (TREC) data. The results did not show a clear correlation between TREC values and the detection of individual specific viruses or viral load values when measured singly. However, a correlation was found between low TREC values and the detection of several different human herpes viruses in the urine in males. We present evidence suggesting that for males, the detection of three or more different human herpes viruses in the urine could identify individuals with declining immune function as evidenced by their significantly lower TREC levels.</p>","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":"21 1","pages":"84"},"PeriodicalIF":5.2,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11606101/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142752025","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}
引用次数: 0
Blood based immune biomarkers associated with clinical frailty scale in older patients with melanoma receiving checkpoint inhibitor immunotherapy. 基于血液的免疫生物标志物与接受检查点抑制剂免疫疗法的老年黑色素瘤患者的临床虚弱程度相关。
IF 5.2 2区 医学
Immunity & Ageing Pub Date : 2024-11-27 DOI: 10.1186/s12979-024-00463-y
Estelle Tran Van Hoi, Saskia J Santegoets, Simon P Mooijaart, Diana Van Heemst, Asli Özkan, Elizabeth M E Verdegaal, Marije Slingerland, Ellen Kapiteijn, Sjoerd H van der Burg, Johanneke E A Portielje, Marij J P Welters, Nienke A de Glas
{"title":"Blood based immune biomarkers associated with clinical frailty scale in older patients with melanoma receiving checkpoint inhibitor immunotherapy.","authors":"Estelle Tran Van Hoi, Saskia J Santegoets, Simon P Mooijaart, Diana Van Heemst, Asli Özkan, Elizabeth M E Verdegaal, Marije Slingerland, Ellen Kapiteijn, Sjoerd H van der Burg, Johanneke E A Portielje, Marij J P Welters, Nienke A de Glas","doi":"10.1186/s12979-024-00463-y","DOIUrl":"10.1186/s12979-024-00463-y","url":null,"abstract":"<p><strong>Introduction: </strong>Immunotherapy with checkpoint inhibition (ICI) is increasingly prescribed to older patients with cancer. High age, especially in combination with frailty, has been associated to immune senescence, which is the age-related decline in immune function, thereby possibly hindering ICI effectiveness. This cross-sectional study aimed to assess whether blood cell immune senescence markers are associated with age, frailty and response to anti-PD-1 treatment in older patients with metastatic melanoma.</p><p><strong>Methods: </strong>In a prospective observational study, sixty patients with stage IIIC or IV melanoma undergoing anti-PD1 treatment were categorized into young (< 65 years; n = 22), old (> 65 years) without frailty (n = 19), and old with frailty (n = 19). In-depth immune cell phenotyping was performed in baseline blood samples (prior to treatment) using multispectral flow cytometry and compared between groups and with immunotherapy treatment response. Antigen-presenting cell capacity was evaluated using mixed lymphocyte reaction and T cell proliferative potential was assessed using PHA proliferation assay.</p><p><strong>Results: </strong>No significant differences in treatment response rates were observed across age groups. Older patients, irrespective of frailty, showed lower levels of naïve CD8 + T cells, with the old and frail group also exhibiting reduced tissue-resident effector memory CD8 + T cells and CD8 + mucosal associated invariant T (MAIT) cells. These differences were not associated with treatment outcomes. T cell proliferation and antigen-presenting cell capacities did not differ across groups.</p><p><strong>Conclusion: </strong>Several ageing and frailty associated changes were detected among circulating immune cells in blood but were not associated with response to immunotherapy in our study. While these findings suggest that the level of frailty and ageing may not necessarily preclude the efficacy of ICI therapy, further investigation is needed to fully understand the impact of frailty and ageing on immunotherapy.</p>","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":"21 1","pages":"83"},"PeriodicalIF":5.2,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11600645/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142734126","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}
引用次数: 0
Elocalcitol mitigates high-fat diet-induced microglial senescence via miR-146a modulation. 艾洛骨化醇通过调节 miR-146a 减轻高脂饮食诱导的小胶质细胞衰老
IF 5.2 2区 医学
Immunity & Ageing Pub Date : 2024-11-22 DOI: 10.1186/s12979-024-00485-6
Keerthana Chithanathan, Monika Jürgenson, Katrina Ducena, Anu Remm, Kalev Kask, Ana Rebane, Li Tian, Alexander Zharkovsky
{"title":"Elocalcitol mitigates high-fat diet-induced microglial senescence via miR-146a modulation.","authors":"Keerthana Chithanathan, Monika Jürgenson, Katrina Ducena, Anu Remm, Kalev Kask, Ana Rebane, Li Tian, Alexander Zharkovsky","doi":"10.1186/s12979-024-00485-6","DOIUrl":"10.1186/s12979-024-00485-6","url":null,"abstract":"<p><strong>Background: </strong>MicroRNAs (miRNAs) play crucial roles in regulating inflammation and cellular senescence. Among them, miR-146a has emerged as a key modulator of inflammation, but its role in obesity-induced senescence remains unexplored. This study investigates the involvement of miR-146a in high-fat diet (HFD)-induced hypothalamic senescence and in protective effects of elocalcitol (Elo), a non-hypercalcemic, fluorinated vitamin D analog on HFD-induced senescence.</p><p><strong>Results: </strong>Wild-type (WT) HFD-fed mice exhibited increased body weight, impaired locomotor activity, and cognitive decline compared to low-fat diet (LFD) controls. In the brain, HFD induced senescence markers (p16, p21), β-galactosidase activity (β-gal) of microglia, and increased expression of senescence associated secretory phenotype (SASP) cytokines (Il1b, Il18, Tnf, Il6) in activated hypothalamic microglia. In the liver, increased p21 and SASP cytokines were detected, although p16 and β-gal levels remained unchanged. Importantly, miR-146a expression was significantly downregulated in the hypothalamus following HFD exposure in WT mice, while miR-146a knockout (Mir146a-/-) mice subjected to HFD showed augmented hypothalamic senescence characterized by higher levels of p16, p21, and β-gal + microglial cells as compared to WT mice. The SASP profile remained similar between Mir146a-/- HFD and WT HFD mice. Among miR-146a target genes, smad4 was upregulated the hypothalamus of HFD-fed mice, with a more pronounced increase in the hypothalamus of HFD-fed Mir146a-/- mice. Further, treatment with Elo upregulated miR-146a expression in both the hypothalamus and the liver, lowered body weight and improved cognitive function, while reducing senescence markers and SASP cytokines in WT HFD mice. These effects were absent in Mir146a-/- HFD mice when treated with Elo, indicating the dependence of Elo's therapeutic efficacy on miR-146a.</p><p><strong>Conclusion: </strong>Elocalcitol prevents development of senescence in microglia via modulation of miR-146a expression, while miR-146a provides protection against HFD-induced cellular senescence in the hypothalamus most probably via inhibition of TGF/Smad4 pathway. These findings highlight Elo and miR-146a as promising therapeutic candidates for ameliorating obesity-related neuroinflammation and senescence.</p>","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":"21 1","pages":"82"},"PeriodicalIF":5.2,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11583547/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142692726","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}
引用次数: 0
Age-related STING suppression in macrophages contributes to increased viral load during influenza a virus infection. 巨噬细胞中与年龄相关的 STING 抑制导致甲型流感病毒感染期间病毒载量增加。
IF 5.2 2区 医学
Immunity & Ageing Pub Date : 2024-11-14 DOI: 10.1186/s12979-024-00482-9
Thurid Lauf, Antje Häder, Franziska Hornung, Yasmina Reisser, Sandor Nietzsche, Fabian Schanz, Verena Trümper, Aldona Jeznach, Sascha Brunke, Torsten Doenst, Tomasz Skirecki, Bettina Löffler, Stefanie Deinhardt-Emmer
{"title":"Age-related STING suppression in macrophages contributes to increased viral load during influenza a virus infection.","authors":"Thurid Lauf, Antje Häder, Franziska Hornung, Yasmina Reisser, Sandor Nietzsche, Fabian Schanz, Verena Trümper, Aldona Jeznach, Sascha Brunke, Torsten Doenst, Tomasz Skirecki, Bettina Löffler, Stefanie Deinhardt-Emmer","doi":"10.1186/s12979-024-00482-9","DOIUrl":"10.1186/s12979-024-00482-9","url":null,"abstract":"<p><p>Ageing is a major risk factor that contributes to increased mortality and morbidity rates during influenza A virus (IAV) infections. Macrophages are crucial players in the defense against viral infections and display impaired function during ageing. However, the impact of ageing on macrophage function in response to an IAV infection remains unclear and offers potential insight for underlying mechanisms. In this study, we investigated the immune response of young and aged human monocyte-derived macrophages to two different H1N1 IAV strains. Interestingly, macrophages of aged individuals showed a lower interferon response to IAV infection, resulting in increased viral load. Transcriptomic data revealed a reduced expression of stimulator of interferon genes (STING) in aged macrophages albeit the cGAS-STING pathway was upregulated. Our data clearly indicate the importance of STING signaling for interferon production by applying a THP-1 STING knockout model. Evaluation of mitochondrial function during IAV infection revealed the release of mitochondrial DNA to be the activator of cGAS-STING pathway. The subsequent induction of apoptosis was attenuated in aged macrophages due to decreased STING signaling. Our study provides new insights into molecular mechanisms underlying age-related immune impairment. To our best knowledge, we are the first to discover an age-dependent difference in gene expression of STING on a transcriptional level in human monocyte-derived macrophages possibly leading to a diminished interferon production.</p>","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":"21 1","pages":"80"},"PeriodicalIF":5.2,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11562583/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142632386","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}
引用次数: 0
Peripheral CD4+ T cell phenotype and brain microglial activation associated with cognitive heterogeneity in aged rats. 与老年大鼠认知异质性相关的外周 CD4+ T 细胞表型和大脑小胶质细胞活化
IF 5.2 2区 医学
Immunity & Ageing Pub Date : 2024-11-14 DOI: 10.1186/s12979-024-00486-5
Lian Yu, Miao-Miao Liu, Mei-Qi Guan, Rui Wang, Xiao-Rong Yang, Xiu-Min Zhang, Jing-Jing Wei, Shu-Fen Wu, Hong Gu, Qiang Fu, Jun-Hong Guo, Yan-Li Li
{"title":"Peripheral CD4<sup>+</sup> T cell phenotype and brain microglial activation associated with cognitive heterogeneity in aged rats.","authors":"Lian Yu, Miao-Miao Liu, Mei-Qi Guan, Rui Wang, Xiao-Rong Yang, Xiu-Min Zhang, Jing-Jing Wei, Shu-Fen Wu, Hong Gu, Qiang Fu, Jun-Hong Guo, Yan-Li Li","doi":"10.1186/s12979-024-00486-5","DOIUrl":"10.1186/s12979-024-00486-5","url":null,"abstract":"<p><p>Cognitive decline is a critical hallmark of brain aging. Although aging is a natural process, there is significant heterogeneity in cognition levels among individuals; however, the underlying mechanisms remain uncertain. In our study, we classified aged male Sprague‒Dawley rats into aged cognition-unimpaired (AU) group and aged cognition-impaired (AI) group by using an attentional set-shifting task. The transcriptome sequencing results of medial prefrontal cortex (mPFC) demonstrated significant differences in microglial activation and inflammatory response pathways between the two groups. Specifically, compared to AU rats, AI rats exhibited a greater presence of CD86-positive microglia and major histocompatibility complex class II (MHC-II)-positive microglia, along with elevated inflammatory molecules, in mPFC. Conversely, AI rats exhibited a reduction in the percentage of microglia expressing CD200R and the anti-inflammatory molecules Arg-1 and TGF-β. Additionally, peripheral blood analysis of AI rats demonstrated elevated levels of Th17 and Th1 cells, along with proinflammatory molecules; however, decreased levels of Treg cells, along with anti-inflammatory molecules, were observed in AI rats. Our research suggested that peripheral Th17/Treg cells and central microglial activation were associated with cognitive heterogeneity in aged rats. These findings may provide a new target for healthy aging.</p>","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":"21 1","pages":"81"},"PeriodicalIF":5.2,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11562703/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142632389","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}
引用次数: 0
Correction: Inflammation scores based on C‑reactive protein and albumin predict mortality in hospitalized older patients independent of the admission diagnosis. 更正:基于 C 反应蛋白和白蛋白的炎症评分可预测住院老年患者的死亡率,与入院诊断无关。
IF 5.2 2区 医学
Immunity & Ageing Pub Date : 2024-11-13 DOI: 10.1186/s12979-024-00483-8
Mirko Di Rosa, Jacopo Sabbatinelli, Angelica Giuliani, Miriam Carella, Daniele Magro, Leonardo Biscetti, Luca Soraci, Francesco Spannella, Massimiliano Fedecostante, Federica Lenci, Elena Tortato, Lorenzo Pimpini, Maurizio Burattini, Sara Cecchini, Antonio Cherubini, Anna Rita Bonfigli, Maria Capalbo, Antonio Domenico Procopio, Carmela Rita Balistreri, Fabiola Olivieri
{"title":"Correction: Inflammation scores based on C‑reactive protein and albumin predict mortality in hospitalized older patients independent of the admission diagnosis.","authors":"Mirko Di Rosa, Jacopo Sabbatinelli, Angelica Giuliani, Miriam Carella, Daniele Magro, Leonardo Biscetti, Luca Soraci, Francesco Spannella, Massimiliano Fedecostante, Federica Lenci, Elena Tortato, Lorenzo Pimpini, Maurizio Burattini, Sara Cecchini, Antonio Cherubini, Anna Rita Bonfigli, Maria Capalbo, Antonio Domenico Procopio, Carmela Rita Balistreri, Fabiola Olivieri","doi":"10.1186/s12979-024-00483-8","DOIUrl":"10.1186/s12979-024-00483-8","url":null,"abstract":"","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":"21 1","pages":"79"},"PeriodicalIF":5.2,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11558870/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142632387","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}
引用次数: 0
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