Immunity & AgeingPub Date : 2024-10-15DOI: 10.1186/s12979-024-00474-9
Feng Xiong, Kai Shen, Di Long, Suqing Zhou, Pinglang Ruan, Yue Xin, Yuezheng Xiao, Weijun Peng, Ming Yang, Haijing Wu, Qianjin Lu
{"title":"Quercetin ameliorates lupus symptoms by promoting the apoptosis of senescent Tfh cells via the Bcl-2 pathway.","authors":"Feng Xiong, Kai Shen, Di Long, Suqing Zhou, Pinglang Ruan, Yue Xin, Yuezheng Xiao, Weijun Peng, Ming Yang, Haijing Wu, Qianjin Lu","doi":"10.1186/s12979-024-00474-9","DOIUrl":"https://doi.org/10.1186/s12979-024-00474-9","url":null,"abstract":"<p><p>Systemic lupus erythematosus (SLE) is an autoimmune disorder that commonly affects the skin, kidneys, joints, and various other systemic tissues, with its development intricately linked to the process of immunosenescence. Quercetin (QC), a phytochemical that occurs naturally, demonstrates many different biological capabilities, such as antibacterial, antioxidant, and anti-inflammatory activities. Our investigation found that QC effectively reduced kidney damage and relieved mesenteric lymph nodes (mLNs) swelling in MRL/lpr lupus mice. Moreover, QC has been found to decrease the number of senescent follicular helper T (Tfh) cells, a pivotal kind of T cells that contribute to the progression of SLE. In vitro, QC exhibited the capacity to modulate mRNA expression levels, with the downregulation of IL-6, IL21-AS1, IL-27, BCL6, and BCL2L12, and the upregulation of FOXP1 and BIM. This modulation resulted in the suppression of Tfh cells differentiation and the enhancement of apoptosis in senescent CD4<sup>+</sup> T cells. In addition, the HuProtTM Human Proteome Microarray revealed that QC can directly bind to BCL-2 protein and therefore promote the apoptosis of senescent CD4<sup>+</sup> T cell. As a result, our investigative elucidate the potent inhibitory action of QC on the ontogeny of Tfh cells, along with its capacity to abrogate the immunosenescent phenotype. This positions QC as a promising therapeutic strategy for treating SLE.</p>","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":"21 1","pages":"69"},"PeriodicalIF":5.2,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11476537/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142480272","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 : 2024-10-09DOI: 10.1186/s12979-024-00471-y
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":"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/s12979-024-00471-y","DOIUrl":"10.1186/s12979-024-00471-y","url":null,"abstract":"<p><p>Systemic inflammation significantly increases the risk of short- and long-term mortality in geriatric hospitalized patients. To predict mortality in older patients with various age-related diseases and infections, including COVID-19, inflammatory biomarkers such as the C-reactive protein (CRP) to albumin ratio (CAR), and related scores and indexes, i.e. Glasgow Prognostic Score (GPS), modified GPS (mGPS), and high sensitivity (hs)-mGPS, have been increasingly utilized. Despite their easy affordability and widespread availability, these biomarkers are predominantly assessed for clinical purposes rather than predictive applications, leading to their underutilization in hospitalized older patients. In this study, we investigated the association of CAR, GPS, mGPS, and hs-mGPS with short-term mortality in 3,206 geriatric hospitalized patients admitted for acute conditions, irrespective of admission diagnosis. We observed that unit increases of CAR, and the highest classes of GPS, mGPS, and hs-mGPS were significantly associated with a two- to threefold increased risk of death, even adjusting the risk for different confounding variables. Interestingly, a hs-mGPS of 2 showed the highest effect size. Furthermore, gender analysis indicated a stronger association between all CRP-albumin based parameters and mortality in men, underscoring the gender-specific relevance of inflammation-based circulating parameters in mortality prediction. In conclusion, scores based on serum CRP and albumin levels offer additional guidance for the stratification of in-hospital mortality risk in older patients by providing additional information on the degree of systemic inflammation.</p>","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":"21 1","pages":"67"},"PeriodicalIF":5.2,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11463076/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142395075","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":"Correction: Melatonin enhances NK cell function in aged mice by increasing T-bet expression via the JAK3-STAT5 signaling pathway.","authors":"Caiying Liang, Rongrong Song, Jieyu Zhang, Jie Yao, Ziyun Guan, Xiaokang Zeng","doi":"10.1186/s12979-024-00470-z","DOIUrl":"10.1186/s12979-024-00470-z","url":null,"abstract":"","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":"21 1","pages":"66"},"PeriodicalIF":5.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11443939/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142362421","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 : 2024-09-30DOI: 10.1186/s12979-024-00469-6
Candice Quin, Jessica A Breznik, Allison E Kennedy, Erica N DeJong, Catherine M Andary, Sofya Ermolina, Donald J Davidson, Jinhui Ma, Michael G Surette, Dawn M E Bowdish
{"title":"Monocyte-driven inflamm-aging reduces intestinal barrier function in females.","authors":"Candice Quin, Jessica A Breznik, Allison E Kennedy, Erica N DeJong, Catherine M Andary, Sofya Ermolina, Donald J Davidson, Jinhui Ma, Michael G Surette, Dawn M E Bowdish","doi":"10.1186/s12979-024-00469-6","DOIUrl":"10.1186/s12979-024-00469-6","url":null,"abstract":"<p><strong>Background: </strong>The intestinal barrier encompasses physical and immunological components that act to compartmentalize luminal contents, such as bacteria and endotoxins, from the host. It has been proposed that an age-related decline of intestinal barrier function may allow for the passage of luminal contents into the bloodstream, triggering a low-grade systemic inflammation termed inflamm-aging. Although there is mounting evidence to support this hypothesis in model species, it is unclear if this phenomenon occurs in humans. In addition, despite being well-established that biological sex impacts aging physiology, its influence on intestinal barrier function and inflamm-aging has not been explored.</p><p><strong>Results: </strong>In this study, we observed sex differences in markers of intestinal barrier integrity, where females had increased epithelial permeability throughout life as compared to males. With age, females had an age-associated increase in circulating bacterial products and metabolites such as LPS and kynurenine, suggesting reduced barrier function. Females also had age-associated increases in established markers of inflamm-aging, including peripheral blood monocytes as well as TNF and CRP. To determine if impaired barrier function was driving inflamm-aging, we performed a mediation analysis. The results show that the loss of intestinal barrier integrity was not the mediator of inflamm-aging in humans. Instead, persistent, low-grade inflammation with age preceded the increase in circulating bacterial products, which we confirmed using animal models. We found, as in humans, that sex modified age-associated increases in circulating monocytes in mice, and that inflammation mediates the loss of intestinal barrier function.</p><p><strong>Conclusion: </strong>Taken together, our results suggest that higher basal intestinal permeability in combination with age-associated inflammation, increases circulating LPS in females. Thus, targeting barrier permeability in females may slow the progression of inflamm-aging, but is unlikely to prevent it.</p>","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":"21 1","pages":"65"},"PeriodicalIF":5.2,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11440997/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142332026","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 : 2024-09-28DOI: 10.1186/s12979-024-00468-7
Anna Tylutka, Barbara Morawin, Natalia Torz, Joanna Osmólska, Kacper Łuszczki, Paweł Jarmużek, Agnieszka Zembron-Lacny
{"title":"Association of adipose tissue inflammation and physical fitness in older adults.","authors":"Anna Tylutka, Barbara Morawin, Natalia Torz, Joanna Osmólska, Kacper Łuszczki, Paweł Jarmużek, Agnieszka Zembron-Lacny","doi":"10.1186/s12979-024-00468-7","DOIUrl":"https://doi.org/10.1186/s12979-024-00468-7","url":null,"abstract":"<p><p>An active lifestyle is of key importance for reduction of obesity and inflammation, as well as circulating levels of adipokines. Therefore, the aim of our study was to assess the relationship of physical fitness with chronic inflammatory status, and to evaluate biomarkers useful in the analysis of adipose tissue dysfunction. Sixty-three older adults (69.6 ± 5.1 years) were allocated to a high n = 31 (women n = 23 and men n = 8 male) or low physical fitness n = 32 (women n = 29 and men n = 3) group based on gait speed values (1.4-1.8 m/s or ≤ 1.3 m/s). The gait speed correlated with hand grip strength (r<sub>s</sub> = 0.493, p = 0.0001) and with leptin level (R = -0.372, p = 0.003), which shows the benefits of physical activity on muscle strength and circulating adipokines. In low physical fitness group, 58.1% individuals had adiponectin to leptin ratio (Adpn/Lep) < 0.5 revealing dysfunction of adipose tissue and high cardiometabolic risk; 20% of the group were obese with BMI ≥ 30 kg/m<sup>2</sup>. In high physical fitness group, 25.8% of individuals had Adpn/Lep ≥ 1.0 i.e., within the reference range. Markers of systemic inflammation were significantly related to physical fitness: CRP/gait speed (r<sub>s</sub> = -0.377) and HMGB-1/gait speed (r<sub>s</sub> = -0.264). The results of the ROC analysis for Adpn (AUC = 0.526), Lep (AUC = 0.745) and HMGB-1 (AUC = 0.689) indicated their diagnostic potential for clinical prognosis in older patients. The optimal threshold values corresponded to 1.2 μg/mL for Adpn (sensitivity 74.2%, specificity 41.9%, OR = 1.4, 95%Cl 0.488-3.902), 6.7 ng/mL for Lep (sensitivity 56.2%, specificity 93.5%, OR = 14.8, 95%Cl 3.574-112.229), 2.63 mg/L for CRP (sensitivity 51.6%, specificity 84.3%, OR = 4.4, 95% Cl 1.401- 16.063) and 34.2 ng/mL for HMGB-1 (sensitivity 62.0%, specificity 86.6%, OR = 12.0, 95%Cl 3.254-61.614). The highest sensitivity and specificity were observed for Leptin and HMGB-1. The study revealed changes in inflammatory status in older adults at various levels of physical fitness and demonstrated diagnostic usefulness of adipokines in the assessment of adipose tissue inflammation.</p>","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":"21 1","pages":"64"},"PeriodicalIF":5.2,"publicationDate":"2024-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11438273/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142332025","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 : 2024-09-14DOI: 10.1186/s12979-024-00466-9
Anne T. Gelderloos, Marije K. Verheul, Irene Middelhof, Mary-Lène de Zeeuw-Brouwer, Robert S. van Binnendijk, Anne-Marie Buisman, Puck B. van Kasteren
{"title":"Repeated COVID-19 mRNA vaccination results in IgG4 class switching and decreased NK cell activation by S1-specific antibodies in older adults","authors":"Anne T. Gelderloos, Marije K. Verheul, Irene Middelhof, Mary-Lène de Zeeuw-Brouwer, Robert S. van Binnendijk, Anne-Marie Buisman, Puck B. van Kasteren","doi":"10.1186/s12979-024-00466-9","DOIUrl":"https://doi.org/10.1186/s12979-024-00466-9","url":null,"abstract":"Previous research has shown that repeated COVID-19 mRNA vaccination leads to a marked increase of SARS-CoV-2 spike-specific serum antibodies of the IgG4 subclass, indicating far-reaching immunoglobulin class switching after booster immunization. Considering that repeated vaccination has been recommended especially for older adults, the aim of this study was to investigate IgG subclass responses in the ageing population and assess their relation with Fc-mediated antibody effector functionality. Spike S1-specific IgG subclass concentrations (expressed in arbitrary units per mL), antibody-dependent NK cell activation, complement deposition and monocyte phagocytosis were quantified in serum from older adults (n = 38–50, 65–83 years) at one month post-second, -third and -fifth vaccination. Subclass distribution in serum was compared to that in younger adults (n = 64, 18–47 years) at one month post-second and -third vaccination. Compared to younger individuals, older adults showed increased levels of IgG2 and IgG4 at one month post-third vaccination (possibly related to factors other than age) and a further increase following a fifth dose. The capacity of specific serum antibodies to mediate NK cell activation and complement deposition relative to S1-specific total IgG concentrations decreased upon repeated vaccination. This decrease associated with an increased IgG4/IgG1 ratio. In conclusion, these findings show that, like younger individuals, older adults produce antibodies with reduced functional capacity upon repeated COVID-19 mRNA vaccination. Additional research is needed to better understand the mechanisms underlying these responses and their potential implications for vaccine effectiveness. Such knowledge is vital for the future design of optimal vaccination strategies in the ageing population.","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":"19 1","pages":""},"PeriodicalIF":7.9,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142259694","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 : 2024-09-12DOI: 10.1186/s12979-024-00467-8
Celia Diaz-Nicieza, Laura Sahyoun, Christina Michalaki, Cecilia Johansson, Fiona J. Culley
{"title":"Ageing results in an exacerbated inflammatory response to LPS by resident lung cells","authors":"Celia Diaz-Nicieza, Laura Sahyoun, Christina Michalaki, Cecilia Johansson, Fiona J. Culley","doi":"10.1186/s12979-024-00467-8","DOIUrl":"https://doi.org/10.1186/s12979-024-00467-8","url":null,"abstract":"Ageing is associated with an increased risk of lung infection and chronic inflammatory lung disease. Innate immune responses are the first line of defence in the respiratory tract, however, age-related changes to innate immunity in the lung are not fully described. Both resident haematopoietic cells, such as alveolar macrophages, and non-haematopoeitic cells, such as epithelial and endothelial cells can contribute to inflammatory and immune responses in the lung. In this study we aimed to determine the impact of ageing on early innate responses of resident cells in the lung. Aged and young mice were inoculated intranasally with lipopolysaccharide (LPS). After 4 h, aged mice recruited higher numbers of neutrophils to the airways and lung. This exacerbated inflammatory response was associated with higher concentrations of chemokines CXCL1, CXCL2 and CCL2 in the airways. Next, precision cut lung slices (PCLS) were stimulated ex vivo with LPS for 16 h. Gene expression of Cxcl2, Tnf and Il1b were all higher in PCLS from aged than young mice and higher levels of secretion of CXCL2 and TNF were detected. To determine which lung cells were altered by age, LPS was intranasally administered to aged and young mice and individual populations of cells isolated by FACS. RT-PCR on sorted cell populations demonstrated higher expression of inflammatory cytokines Cxcl2, Ccl2 and Tnf in epithelial cells and alveolar macrophages and higher expression of Cxcl2 by endothelial cells of aged mice compared to young. These differences in expression of pro-inflammatory cytokines did not correspond to higher levels of Tlr4 expression. Ageing leads to a heightened neutrophilic inflammatory response in the lung after LPS exposure, and higher expression and production of pro-inflammatory cytokines by resident lung cells, including alveolar macrophages, epithelial cells and endothelial cells. The responses of multiple resident lung cell populations are altered by aging and contribute to the exacerbated inflammation in the lung following LPS challenge. This has implications for our understanding of respiratory infections and inflammation in older people.","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":"8 1","pages":""},"PeriodicalIF":7.9,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142176292","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 : 2024-09-11DOI: 10.1186/s12979-024-00465-w
Jordyn S. Barr, Lindsay E. Martin, Ann T. Tate, Julián F. Hillyer
{"title":"Warmer environmental temperature accelerates aging in mosquitoes, decreasing longevity and worsening infection outcomes","authors":"Jordyn S. Barr, Lindsay E. Martin, Ann T. Tate, Julián F. Hillyer","doi":"10.1186/s12979-024-00465-w","DOIUrl":"https://doi.org/10.1186/s12979-024-00465-w","url":null,"abstract":"Most insects are poikilotherms and ectotherms, so their body temperature is predicated by environmental temperature. With climate change, insect body temperature is rising, which affects how insects develop, survive, and respond to infection. Aging also affects insect physiology by deteriorating body condition and weakening immune proficiency via senescence. Aging is usually considered in terms of time, or chronological age, but it can also be conceptualized in terms of body function, or physiological age. We hypothesized that warmer temperature decouples chronological and physiological age in insects by accelerating senescence. To investigate this, we reared the African malaria mosquito, Anopheles gambiae, at 27 °C, 30 °C and 32 °C, and measured survival starting at 1-, 5-, 10- and 15-days of adulthood after no manipulation, injury, or a hemocoelic infection with Escherichia coli or Micrococcus luteus. Then, we measured the intensity of an E. coli infection to determine how the interaction between environmental temperature and aging shapes a mosquito’s response to infection. We demonstrate that longevity declines when a mosquito is infected with bacteria, mosquitoes have shorter lifespans when the temperature is warmer, older mosquitoes are more likely to die, and warmer temperature marginally accelerates the aging-dependent decline in survival. Furthermore, we discovered that E. coli infection intensity increases when the temperature is warmer and with aging, and that warmer temperature accelerates the aging-dependent increase in infection intensity. Finally, we uncovered that warmer temperature affects both bacterial and mosquito physiology. Warmer environmental temperature accelerates aging in mosquitoes, negatively affecting both longevity and infection outcomes. These findings have implications for how insects will serve as pollinators, agricultural pests, and disease vectors in our warming world.","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":"87 1","pages":""},"PeriodicalIF":7.9,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142176293","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 : 2024-09-10DOI: 10.1186/s12979-024-00462-z
Sarah Talley, Tyler Nguyen, Lily Van Ye, Rasa Valiauga, Jake DeCarlo, Jabra Mustafa, Benjamin Cook, Fletcher A. White, Edward M. Campbell
{"title":"Characterization of age-associated inflammasome activation reveals tissue specific differences in transcriptional and post-translational inflammatory responses","authors":"Sarah Talley, Tyler Nguyen, Lily Van Ye, Rasa Valiauga, Jake DeCarlo, Jabra Mustafa, Benjamin Cook, Fletcher A. White, Edward M. Campbell","doi":"10.1186/s12979-024-00462-z","DOIUrl":"https://doi.org/10.1186/s12979-024-00462-z","url":null,"abstract":"Aging is associated with systemic chronic, low-grade inflammation, termed ‘inflammaging’. This pattern of inflammation is multifactorial and is driven by numerous inflammatory pathways, including the inflammasome. However, most studies to date have examined changes in the transcriptomes that are associated with aging and inflammaging, despite the fact that inflammasome activation is driven by a series of post-translational activation steps, culminating in the cleavage and activation of caspase-1. Here, we utilized transgenic mice expressing a caspase-1 biosensor to examine age-associated inflammasome activation in various organs and tissues to define these post-translational manifestations of inflammaging. Consistent with other studies, we observe increased inflammation, including inflammasome activation, in aged mice and specific tissues. However, we note that the degree of inflammasome activation is not uniformly associated with transcriptional changes commonly used as a surrogate for inflammasome activation in tissues. Furthermore, we used a skull thinning technique to monitor central nervous system inflammasome activation in vivo in aged mice and found that neuroinflammation is significantly amplified in aged mice in response to endotoxin challenge. Together, these data reveal that inflammaging is associated with both transcriptional and post-translational inflammatory pathways that are not uniform between tissues and establish new methodologies for measuring age-associated inflammasome activation in vivo and ex vivo.","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":"76 1","pages":""},"PeriodicalIF":7.9,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142176344","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":"Melatonin enhances NK cell function in aged mice by increasing T-bet expression via the JAK3-STAT5 signaling pathway.","authors":"Caiying Liang, Rongrong Song, Jieyu Zhang, Jie Yao, Ziyun Guan, Xiaokang Zeng","doi":"10.1186/s12979-024-00459-8","DOIUrl":"10.1186/s12979-024-00459-8","url":null,"abstract":"<p><p>Natural killer (NK) cells are crucial innate immune cells that provide defense against viruses and tumors. However, aging is associated with alterations in NK cell composition and compromised cell functions. Melatonin, known for its anti-tumor effects, has been reported to improve NK cell function. However, the molecular mechanism underlying melatonin's effect on senescent NK cells remains unclear. In this study, we aimed to elucidate the mechanism by which melatonin enhances the function of senescent NK cells. Our findings revealed that melatonin significantly increased the number and function of NK cells in aging mice. The results suggest that melatonin enhances NK cell proliferation, degranulation, and IFN-γ secretion. Further investigations demonstrated that melatonin promotes NK cell maturation and activation, mainly via the JAK3/STAT5 signaling pathway, leading to increased expression of T-bet. These discoveries provide a theoretical basis for potential immunotherapy strategies based on melatonin-mediated modulation of NK cell function in aging individuals.</p>","PeriodicalId":51289,"journal":{"name":"Immunity & Ageing","volume":"21 1","pages":"59"},"PeriodicalIF":5.2,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11375890/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142141708","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}