Immunity & Ageing最新文献

{"title":"Diverging effects of tumor necrosis factor inhibitors and conventional synthetic disease-modifying antirheumatic drugs on immunosenescence and inflammageing in rheumatoid arthritis: a cross-sectional analysis.","authors":"Tobias Schwarz, Giovanni Almanzar, Sebastian Völkl, Martin Feuchtenberger, Johannes Leierer, Christian Schmidt, Frank Deininger, Hans-Peter Tony, Marc Schmalzing, Martina Prelog","doi":"10.1186/s12979-025-00508-w","DOIUrl":"10.1186/s12979-025-00508-w","url":null,"abstract":"<p><strong>Background: </strong>Immunosenescence is characterized by a decline in naive T cells, a reduced T cell receptor repertoire, and the accumulation of terminally-differentiated and unspecifically-activated proinflammatory cells, a process called inflammageing. Premature immunosenescence is thought to be pathogenetically relevant in rheumatoid arthritis (RA), either by posing a risk factor for its development, or by advancing the rheumatic disease as a result of excess antigenic and inflammatory stimulation. We investigated parameters of immunosenescence in RA patients treated with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) only compared to patients treated additionally or exclusively with a tumor necrosis factor inhibitor (TNFi) and age-matched healthy controls to investigate the effect of RA treatment on age-associated T cell phenotypes and functions.</p><p><strong>Results: </strong>The csDMARD-only treated patients, compared to the TNFi-treated patients and healthy controls, displayed an enhanced age-dependent decline in CD31⁺ recent thymic emigrants (RTE) and Interleukin-7 (IL-7)-receptor α-chain (CD127)-expressing CD4⁺ T cells participating in IL-7-associated homeostatic proliferation, a diminished proliferation of RTE and CD127⁺ T cells, as well as reduced T cell receptor excision circle (TREC) counts. However, whereas the RA patients exhibited reduced proportions of unspecifically activated IFNγ- and IL-17-producing T cells, TNFi initiation induced an increase in these proinflammatory cells.</p><p><strong>Conclusions: </strong>Whereas a TNFi treatment seems to counteract the non-inflammatory aspects of immunosenescence, it induces increasing proportions of terminally-differentiated, cytokine-producing effector memory T cells, requiring awareness as possibly contributing to secondary autoimmune phenomena in RA.</p>","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":"22 1","pages":"21"},"PeriodicalIF":5.2,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12096643/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144129545","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":"Gut-vitamin D interplay: key to mitigating immunosenescence and promoting healthy ageing.","authors":"Hammad Ullah","doi":"10.1186/s12979-025-00514-y","DOIUrl":"10.1186/s12979-025-00514-y","url":null,"abstract":"<p><strong>Background: </strong>Immunosenescence is the loss and change of immunological organs, as well as innate and adaptive immune dysfunction with ageing, which can lead to increased sensitivity to infections, age-related diseases, and cancer. Emerging evidence highlights the role of gut-vitamin D axis in the regulation of immune ageing, influencing chronic inflammation and systemic health. This review aims to explore the interplay between the gut microbiota and vitamin D in mitigating immunosenescence and preventing against chronic inflammation and age-related diseases.</p><p><strong>Main text: </strong>Gut microbiota dysbiosis and vitamin D insufficiency accelerate immunosenescence and risk of chronic diseases. Literature data reveal that vitamin D modulates gut microbiota diversity and composition, enhances immune resilience, and reduce systemic inflammation. Conversely, gut microbiota influences vitamin D metabolism to promote the synthesis of active vitamin D metabolites with implications for immune health.</p><p><strong>Conclusions: </strong>These findings underscore the potential of targeting gut-vitamin D axis to modulate immune responses, delay the immune ageing, and mitigate age-related diseases. Further research is needed to integrate vitamin D supplementation and microbiome modulation into strategies aimed at promoting healthy ageing.</p>","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":"22 1","pages":"20"},"PeriodicalIF":5.2,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12087203/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144103021","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":"Zinc deficiency as possible link between immunosenescence and age-related diseases.","authors":"Michael Tobias Schulz, Lothar Rink","doi":"10.1186/s12979-025-00511-1","DOIUrl":"10.1186/s12979-025-00511-1","url":null,"abstract":"<p><p>As global life expectancy increases, research reveals a critical challenge in aging: the progressive deterioration of immune function, termed immunosenescence. This age-related immune decline is characterized by a complex dysregulation of immune responses, which leaves older adults increasingly vulnerable to infections, chronic inflammatory states, and various degenerative diseases. Without intervention, immunosenescence significantly contributes to morbidity and mortality among the elderly, intensifying healthcare burdens and diminishing quality of life on both individual and societal levels. This review explores the essential role of zinc, a trace element critical for immune health, in mitigating the impact of immunosenescence and slowing the cascade of immunological dysfunctions associated with aging. By modulating the activity of key immune cells and pathways, zinc supplementation emerges as a promising approach to strengthen immunity, reduce oxidative stress, and counteract \"inflammaging,\" a state of chronic, low-grade inflammation that accelerates tissue damage and drives disease progression. Zinc's involvement in cellular defense and repair mechanisms across the immune system highlights its ability to enhance immune cell functionality, resilience, and adaptability, strengthening the body's resistance to infection and its ability to manage stressors that contribute to diseases of aging. Indeed, zinc has demonstrated potential to improve immune responses, decrease inflammation, and mitigate the risk of age-related conditions including diabetes, depression, cardiovascular disease, and vision loss. Given the prevalent barriers to adequate zinc intake among older adults, including dietary limitations, decreased absorption, and interactions with medications, this review underscores the urgent need to address zinc deficiency in aging populations. Recent findings on zinc's cellular and molecular effects on immune health present zinc supplementation as a practical, accessible intervention for supporting healthier aging and improving quality of life. By integrating zinc into targeted strategies, public health efforts may not only sustain immunity in the elderly but also extend healthy longevity, reduce healthcare costs, and potentially mitigate the incidence and impact of chronic diseases that strain healthcare systems worldwide.</p>","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":"22 1","pages":"19"},"PeriodicalIF":5.2,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12087153/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144103025","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":"The immunological age prediction of monocytes indicates that gestational diabetes mellitus accelerates the aging of monocytes in offspring.","authors":"Yan Zhang, Rui Guo, Min Yin, Mei Shi, Ting Zhong, Shanshan Liu, Xia Li","doi":"10.1186/s12979-025-00513-z","DOIUrl":"10.1186/s12979-025-00513-z","url":null,"abstract":"<p><strong>Background: </strong>Recent studies have suggested that gestational diabetes mellitus (GDM) can accelerate cellular aging in multiple cell types in offspring, but its impact on immune senescence remains uncertain. Our prior study reveals GDM increased the secretion of inflammatory factors by monocytes in offspring. This study discovered the transcriptome characteristics of aging monocytes at the single-cell level and explore the impact of GDM on the progression of monocyte aging in offspring.</p><p><strong>Method: </strong>Single-cell sequencing data from 56 healthy individuals (aged 0-100 years), comprising self-measured samples (n = 6) and publicly available datasets from the Gene Expression Omnibus (GEO, n = 50), were analyzed to characterize monocyte senescence. Linear mixed-effects modeling was used to screen for age-related genes. A random forest model was created to predict immune age in monocytes, allowing for quantitative assessment of aging.</p><p><strong>Results: </strong>We detected an increase in the number of inflammatory monocytes expressing IL1B and CXCL8 with age. Two age-related gene expression patterns were identified in monocytes. Analysis of offspring monocytes from mothers with GDM suggested that exposure to a GDM environment in the womb may lead to increased expression of aging-related genes, a hindered cell cycle, and increased immune age. The immune age of monocytes at birth is significantly linked to maternal weight gain, high fasting blood glucose levels, and cord blood C-peptide levels during pregnancy.</p><p><strong>Conclusions: </strong>Exposure to GDM during pregnancy accelerates aging in offspring immune cells. Monitoring maternal weight and blood sugar during GDM can help prevent negative effects on the offspring immune system.</p>","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":"22 1","pages":"18"},"PeriodicalIF":5.2,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12070592/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143994058","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":"Immunological enhancement of micro-nanoparticle formulated with risedronate and zinc as vaccine adjuvant in aged mice.","authors":"Yue Liu, Man Yang, Meifeng Nie, Shuyu Wu, Rong Su, Dekui Qiu, Shouneng Lu, Hualong Xiong, Jinlei Zhang, Shengxiang Ge, Quan Yuan, Qinjian Zhao, Tianying Zhang, Yingbin Wang, Ningshao Xia","doi":"10.1186/s12979-025-00512-0","DOIUrl":"10.1186/s12979-025-00512-0","url":null,"abstract":"<p><strong>Background: </strong>Elderly individuals face heightened susceptibility to infectious diseases and diminished vaccine responses. Vaccine adjuvants offer a solution. Despite aluminum adjuvant's long history, its limitations in inducing strong cellular immunity and protecting immunocompromised individuals restrict its application. Building upon our previous development of zinc salt particle-based risedronate (Zn-RS), we systematically investigated the immunoenhancing effects of Zn-RS in aged mice and thoroughly explored the underlying mechanisms responsible for these observations in this study.</p><p><strong>Results: </strong>Compared to formulations using aluminum adjuvant, Zn-RS combined with either varicella-zoster virus glycoprotein E (gE) or SARS-CoV-2 monovalent STFK protein (STFK) elicited significantly higher IgG and neutralization titers, as well as superior long-term humoral immunity. Moreover, Zn-RS induced greater quantities of dendritic cells (DCs), antigen-presenting cells (APCs), follicular helper T (T_FH) cells, Th1/Th2/Th9/Th17 type immune cells, germinal center B cells (GCBs) and plasma cells.</p><p><strong>Conclusions: </strong>These findings support Zn-RS as a promising adjuvant candidate for elderly populations, warranting further exploration of its mechanisms and potential applications.</p>","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":"22 1","pages":"17"},"PeriodicalIF":5.2,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12070681/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144043004","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":"Pentraxin-3 and C-reactive protein plasma levels predict survival in older adults with or without metabolic syndrome - results of the PolSenior2 substudy.","authors":"Aleksander J Owczarek, Anna Ochman, Anna Chudek, Małgorzata Mossakowska, Monika Puzianowska-Kuźnicka, Hanna Kujawska-Danecka, Tomasz Zdrojewski, Andrzej Więcek, Jerzy Chudek, Magdalena Olszanecka-Glinianowicz","doi":"10.1186/s12979-025-00509-9","DOIUrl":"https://doi.org/10.1186/s12979-025-00509-9","url":null,"abstract":"<p><strong>Objective: </strong>There are no published data on the associations between plasma concentration of pentraxin-3 (PTX-3) - a marker of vascular inflammation and mortality in older subjects with or without metabolic syndrome (MS). Therefore, we aimed to compare the prognostic significance of increased PTX-3 and CRP levels on overall survival in subjects aged 60 and older with and without MS.</p><p><strong>Materials and methods: </strong>Study participants (N = 3534) were categorized according to the presence or absence of MS and then each of these groups was stratified into 3 subgroups based on concentrations of CRP (≤ 3 mg/dL and > 3 mg/dL) and PTX-3 (< and ≥ the sex-specific cut-off values, based on the ROC curve analysis with the Youden index): double-negative inflammatory markers (low CRP and PTX-3 plasma concentrations); single-positive inflammatory marker (increased CRP or PTX-3 plasma concentrations) and double-positive inflammatory markers subgroup (increased CRP and PTX-3 plasma concentrations). During the 4.19-year follow-up, 678 (19.2% of the entire cohort) individuals died including 401 men (22.9%) and 277 women (15.5% ).</p><p><strong>Results: </strong>The optimal cut-off for PTX-3 plasma concentration associated with an increased risk of death was 2.07 ng/mL for men and 2.23 ng/mL for women. The death rates were increased for single-positive and were highest in double-positive subgroups both for men and women, with or without MS. Kaplan-Meier analysis showed no effect of MS on survival in men and women in subgroups within specific inflammatory marker categories. Of note, the inflammatory markers class effect on survival was already significant in the single-positive subgroups (34% and 44% higher risk for death for men and women), and even more pronounced for the double-positive subgroup (more than two and almost three times higher risk of death for men and women, respectively). In the entire study group, a weak correlation was found between plasma concentrations of PTX-3 and hs-CRP (ρ = 0.11, p < 0.001) and slightly higher in undernourished subjects with hs-CRP > 3 mg/dL (ρ = 0.28, p < 0.001).</p><p><strong>Conclusion: </strong>Our study suggests that in the age-advanced Caucasian population, the inflammatory status with increased plasma levels of both PTX-3 and CRP is associated with a higher risk of all-cause mortality, regardless of the occurrence of MS. However, due to the retrospective study design, these results require confirmation in prospective studies with an analysis of the underlying causes of death.</p>","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":"22 1","pages":"16"},"PeriodicalIF":5.2,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12060356/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144040262","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":"Chronic IL-21 drives neuroinflammation and promotes lipid accumulation in microglia.","authors":"Hugo Oyamada, Yinzhi Ying, Sudhanshu Agrawal, Aizhu Liu, Veedamali S Subramanian, Cleonice Alves de Melo Bento, Anshu Agrawal","doi":"10.1186/s12979-025-00510-2","DOIUrl":"https://doi.org/10.1186/s12979-025-00510-2","url":null,"abstract":"<p><p>Neuroinflammation is a key contributor to the onset and progression of neurodegenerative diseases, driven by factors such as viral infections, autoimmune disorders, and peripheral inflammation. However, the mechanisms linking peripheral inflammation or viral infections to neuroinflammation remain poorly understood, limiting the development of effective therapies. Proinflammatory cytokines are implicated in these processes but their effects on brain cells, including microglia, remain insufficiently characterized. Here, we demonstrate that IL-21, a proinflammatory cytokine elevated in autoimmune disorders, chronic viral infections, and Alzheimer's disease, activates microglia and promotes lipid accumulation within these cells. Young, healthy mice injected with IL-21 to mimic chronic exposure exhibited increased proinflammatory cytokine levels and microglial activation in the brain. Notably, microglia in these mice displayed enhanced lipid accumulation, accompanied by upregulation of lipid uptake receptors such as CD36 and TREM-2. These findings were corroborated using the human microglial cell line HMC-3, where IL-21 exposure similarly induced lipid accumulation and increased expression of CD36 and ApoE. Mechanistic investigations revealed that IL-21 upregulates HIF-1α, a transcription factor critical for lipid metabolism and lipid droplet formation. Additionally, we observed elevated IL-21 levels in the circulation of elderly individuals compared to younger counterparts, with IL-21 increases associated with CMV seropositivity. Aged mouse brains mirrored the microglial lipid accumulation and activation patterns seen in IL-21-injected mice. In summary, we identify a novel IL-21-driven mechanism involving lipid accumulation in microglia that contributes to neuroinflammation.</p>","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":"22 1","pages":"15"},"PeriodicalIF":5.2,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12039274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144059297","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":"Old hematopoietic stem cells retain competence to reconstitute a youthful B cell system that is highly responsive to protein-based vaccination.","authors":"Paul Kunath, Dominik Pflumm, Bettina Moehrle, Vadim Sakk, Alina Seidel, Jan Münch, Hartmut Geiger, Reinhold Schirmbeck","doi":"10.1186/s12979-025-00507-x","DOIUrl":"10.1186/s12979-025-00507-x","url":null,"abstract":"<p><strong>Background: </strong>Ageing-associated remodeling of the murine B cell system is accompanied with a reduction of CD19⁺ B cells such as follicular B cells (FOB) and an accumulation of age-associated B cells (ABC) or activated B cell subsets. This remodeling is thought to confer an attenuated antibody response, such as to SARS-CoV-2 spike (S) vaccines in both aged mice and humans. To gain insight into the de novo development and function of an old B cell system, we reconstituted young and old immune systems by transferring hematopoietic stem cells (HSCs) from immune-competent young (2-3 months) CD45.1⁺ donors (DY-HSC) or old (20-24 months) donors (DO-HSC) into T and B cell-deficient young recipient CD45.2⁺ RAG1^-/- mice, followed by protein-based vaccination.</p><p><strong>Results: </strong>In the same environment of young RAG1^-/- mice, transplanted DO-HSCs compared to DY-HSCs reconstituted lower numbers of CD19⁺ B cells and CD45.1⁺ cells, though the engraftment of donor-derived HSCs in the young bone marrow (BM) was very similar. Furthermore, indicative for youthful and unchallenged B cell systems, and in contrast to aged mice, very low levels of antigen-experienced memory B cells or age-associated B cells (ABC) developed in both DY-HSC and DO-HSC hosts. The commercially available recombinant SARS-CoV-2 S vaccine (NVX-CoV2373) induced lower IgG⁺ S-antibody titers and pseudovirus neutralization activity in old compared to young mice. In contrast, very similar high IgG⁺ S-antibody titers were induced in DO-HSC and DY-HSC hosts, and pseudovirus neutralization activity was even enhanced in DO-HSC compared with DY-HSC hosts.</p><p><strong>Conclusions: </strong>Both DO-HSCs and DY-HSCs established in the young recipient BM to a similar extend, suggesting that the concomitant reduction in the de novo reconstitution of CD19⁺ B cells in DO-HSC vs. DY-HSC transplanted animals is specifically related to old HSCs. DO-HSCs and DY-HSCs reconstitute very similar unchallenged B cell systems that efficiently elicit antigen-specific IgG antibodies by protein-based vaccination. Old HSCs thus retain competence to reconstitute a youthful and functional B cell system, at least in the young environment of transplanted RAG1^-/- mice. This suggests that it is primarily age-related factors, and not HSCs per se, that influence the composition and functionality of the old B cell system.</p>","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":"22 1","pages":"14"},"PeriodicalIF":5.2,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11971919/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143789407","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":"Enhancing flu vaccine responses in older adults: preliminary insights from the ISOLDA study on immunosenescence and antioxidant and anti-inflammatory approaches.","authors":"Anna Aiello, Anna Calabrò, Mattia Emanuela Ligotti, Giulia Accardi, Mojtaba Shekarkar Azgomi, Nadia Caccamo, Calogero Caruso, Francesco Dieli, Marco Pio La Manna, Antonio Procopio, Giuseppina Candore","doi":"10.1186/s12979-025-00506-y","DOIUrl":"10.1186/s12979-025-00506-y","url":null,"abstract":"<p><p>Aging is frequently characterized by an inadequate primary vaccine response, likely due to immunosenescence and inflamm-aging, a low-level, chronic inflammatory state. Both aspects increase the susceptibility of older adults to viral and bacterial infections, resulting in a higher frequency and severity of infectious diseases. In this preliminary study, a cohort of 52 individuals was recruited and divided into two groups: young (age range 21-35) and older adults (> 60 years old). Peripheral blood mononuclear cells (PBMCs) were collected before (time 0, T0) and after (time 1, T1) the immunization with a tetravalent influenza vaccine. Then, T cell immunophenotyping analysis was conducted to investigate how aging and influenza vaccination influence T cell responses. Additionally, the anti-inflammatory and antioxidant effects of oleuropein (OLE), a secoiridoid extracted from extra virgin olive oil, alone or in combination with BIRB 796, a potent inhibitor of p38 MAPK, were explored to enhancing the impact of influenza virus on T cell activation, aiming to identify potential alternatives or complementary strategies to improve traditional flu-vaccine formulations. Statistically significant observations were noted for a decrement in CD8 + T naïve and an increase of effector memory between the young and older adults after flu-vaccination. Moreover, preliminary findings indicate anti-inflammatory and antioxidant properties of OLE and BIRB 796 on T cell responses, particularly regarding Reactive Oxygen Species/Reactive Nitrogen Species modulation, with a trend toward the decrease of pro-inflammatory cytokines (i.e., Interferon-γ (INF-γ), Tumor Necrosis Factor-α (TNF-α)), αalthough without statistical significance.</p>","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":"22 1","pages":"13"},"PeriodicalIF":5.2,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11938677/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143722437","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":"Delayed viral clearance and altered inflammatory responses affect severity of SARS-CoV-2 infection in aged mice.","authors":"Émile Lacasse, Isabelle Dubuc, Leslie Gudimard, Ana Claudia Dos S P Andrade, Annie Gravel, Karine Greffard, Alexandre Chamberland, Camille Oger, Jean-Marie Galano, Thierry Durand, Éric Philipe, Marie-Renée Blanchet, Jean-François Bilodeau, Louis Flamand","doi":"10.1186/s12979-025-00503-1","DOIUrl":"10.1186/s12979-025-00503-1","url":null,"abstract":"<p><p>Epidemiological investigations consistently demonstrate an overrepresentation of the elderly in COVID-19 hospitalizations and fatalities, making the advanced age as a major predictor of disease severity. Despite this, a comprehensive understanding of the cellular and molecular mechanisms explaining how old age represents a major risk factor remain elusive. To investigate this, we compared SARS-CoV-2 infection outcomes in young adults (2 months) and geriatric (15-22 months) mice. Both groups of K18-ACE2 mice were intranasally infected with 500 TCID₅₀ of SARS-CoV-2 Delta variant with analyses performed on days 3, 5, and 7 post-infection (DPI). Analyses included pulmonary cytokines, lung RNA-seq, viral loads, lipidomic profiles, and histological assessments, with a concurrent evaluation of the percentage of mice reaching humane endpoints. The findings unveiled notable differences, with aged mice exhibiting impaired viral clearance, reduced survival, and failure to recover weight loss due to infection. RNA-seq data suggested greater lung damage and reduced respiratory function in infected aged mice. Additionally, elderly-infected mice exhibited a deficient antiviral response characterized by reduced Th1-associated mediators (IFNγ, CCL2, CCL3, CXCL9) and diminished number of macrophages, NK cells, and T cells. Furthermore, mass-spectrometry analysis of the lung lipidome indicated altered expression of several lipids with immunomodulatory and pro-resolution effects in aged mice such as Resolvin, HOTrEs, and NeuroP, but also DiHOMEs-related ARDS. These findings indicate that aging affects antiviral immunity, leading to prolonged infection, greater lung damage, and poorer clinical outcomes. This underscores the potential efficacy of immunomodulatory treatments for elderly subjects experiencing symptoms of severe COVID-19.</p>","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":"22 1","pages":"11"},"PeriodicalIF":5.2,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11899864/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143617760","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}