Immune Senescence Research Articles

Identification of potential immunotherapeutic targets and prognostic biomarkers in Graves' disease using weighted gene co-expression network analysis

Graves' disease (GD) is an autoimmune disorder characterized by hyperthyroidism resulting from autoantibody-induced stimulation of the thyroid gland. Despite recent advancements in understanding GD's pathogenesis, the molecular processes driving disease progression and treatment response remain poorly understood. In this study, we aimed to identify crucial immunogenic factors associated with GD prognosis and immunotherapeutic response. To achieve this, we implemented a comprehensive screening strategy that combined computational immunogenicity-potential scoring with multi-parametric cluster analysis to assess the immunomodulatory genes in GD-related subtypes involving stromal and immune cells. Utilizing weighted gene co-expression network analysis (WGCNA), we identified co-expressed gene modules linked to cellular senescence and immune infiltration in CD4+ and CD8+ GD samples. Additionally, gene set enrichment analysis enabled the identification of hallmark pathways distinguishing high- and low-immune subtypes. Our WGCNA analysis revealed 21 gene co-expression modules comprising 1,541 genes associated with immune infiltration components in various stages of GD, including T cells, M1 and M2 macrophages, NK cells, and Tregs. These genes primarily participated in T cell proliferation through purinergic signaling pathways, particularly neuroactive ligand-receptor interactions, and DNA binding transcription factor activity. Three genes, namely PRSS1, HCRTR1, and P2RY4, exhibited robustness in GD patients across multiple stages and were involved in immune cell infiltration during the late stage of GD (p < 0.05). Importantly, HCRTR1 and P2RY4 emerged as potential prognostic signatures for predicting overall survival in high-immunocore GD patients (p < 0.05). Overall, our study provides novel insights into the molecular mechanisms driving GD progression and highlights potential key immunogens for further investigation. These findings underscore the significance of immune infiltration-related cellular senescence in GD therapy and present promising targets for the development of new immunotherapeutic strategies.

Intestinal Permeability, Gut Inflammation, and Gut Immune System Response Are Linked to Aging-Related Changes in Gut Microbiota Composition: A Study in Female Mice.

Aging entails changes at the cellular level that increase the risk of various pathologies. An association between gut microbiota and age-related diseases has also been attributed. This study aims to analyze changes in fecal microbiota composition and their association with genes related to immune response, gut inflammation, and intestinal barrier impairment. Fecal samples of female mice at different ages (2 months, 6 months, 12 months, and 18 months) and gene expression in colon tissue were analyzed. Results showed that the older mice group had a more diverse microbiota than the younger group. Additionally, the abundance of Cyanobacteria, Proteobacteria, Flavobacteriaceae, Bacteroides, Parabacteroides, Prevotellaceae_UCG-001, Akkermansia, and Parabacteroides goldsteinii increased with age. In contrast, there was a notable decline in Clostridiaceae, Lactobacillaceae, Monoglobaceae, Ligilactobacillus, Limosilactobacillus, Mucispirillum, and Bacteroides faecichinchillae. These bacteria imbalances were positively correlated with increased inflammation markers in the colon, including Tnf-α, Ccl2, and Ccl12, and negatively with the expression of tight junction genes (Jam2, Tjp1, and Tjp2), as well as immune response genes (Cd4, Cd72, Tlr7, Tlr12, and Lbp). In conclusion, high levels of diversity did not result in improved health in older mice; however, the imbalance in bacteria abundance that occurs with aging might contribute to immune senescence, inflammation, and leaky gut disease.

Immune aging: biological mechanisms, clinical symptoms, and management in lung transplant recipients.

While chronologic age can be precisely defined, clinical manifestations of advanced age occur in different ways and at different rates across individuals. The observed phenotype of advanced age likely reflects a superposition of several biological aging mechanisms which have gained increasing attention as the world contends with an aging population. Even within the immune system, there are multiple age-associated biological mechanisms at play, including telomere dysfunction, epigenetic dysregulation, immune senescence programs, and mitochondrial dysfunction. These biological mechanisms have associated clinical syndromes, such as telomere dysfunction leading to short telomere syndrome (STS), and optimal patient management may require recognition of biologically based aging syndromes. Within the clinical context of lung transplantation, select immune aging mechanisms are particularly pronounced. Indeed, STS is increasingly recognized as an indication for lung transplantation. At the same time, common aging phenotypes may be evoked by the stress of transplantation because lung allografts face a potent immune response, necessitating higher levels of immune suppression and associated toxicities, relative to other solid organs. Age-associated conditions exacerbated by lung transplant include bone marrow suppression, herpes viral infections, liver cirrhosis, hypogammaglobulinemia, frailty, and cancer risk. This review aims to dissect the molecular mechanisms of immune aging and describe their clinical manifestations in the context of lung transplantation. While these mechanisms are more likely to manifest in the context of lung transplantation, this mechanism-based approach to clinical syndromes of immune aging has broad relevance to geriatric medicine.

Anticipation and Verification of Dendrobium-Derived Nanovesicles for Skin Wound Healing Targets, Predicated Upon Immune Infiltration and Senescence.

Dendrobium, with profound botanical importance, reveals a rich composition of bioactive compounds, including polysaccharides, flavonoids, alkaloids, and diverse amino acids, holding promise for skin regeneration. However, the precise mechanism remains elusive. Seeking a potent natural remedy for wound healing, exocyst vesicles were successfully isolated from Dendrobium. This investigation aimed to employ bioinformatics and in vivo experiments to elucidate target genes of Dendrobium-derived nanovesicles in skin wound healing, focusing on immune infiltration and senescence characteristics. C57 mice experienced facilitated wound healing through Dendrobium-derived nanovesicles (DDNVs). Bioinformatics analysis and GEO database mining identified crucial genes by intersecting immune-related, senescence-related, and PANoptosis-associated genes. The identified genes underwent in vivo validation. DDNVs remarkably accelerated skin wound healing in C57 mice. Bioinformatics analysis revealed abnormal expression patterns of immune-related, senescence-related, and pan-apoptosis-related genes, highlighting an overexpressed IL-1β and downregulated IL-18 in the model group, Exploration of signaling pathways included IL-17, NF-kappa B, NOD-like receptor, and Toll-like receptor pathways. In vivo experiments confirmed DDNVs' efficacy in suppressing IL-1β expression, enhancing wound healing. Plant-derived nanovesicles (PDNV) emerged as a natural, reliable, and productive approach to wound healing. DDNVs uptake by mouse skin tissues, labeled with a fluorescent dye, led to enhanced wound healing in C57 mice. Notably, IL-1β overexpression in immune cells and genes played a key role. DDNVs intervention effectively suppressed IL-1β expression, accelerating skin wound tissue repair.

Accelerated Neuroimmune Dysfunction in Aged HIV-1-Infected Humanized Mice.

Disordered immunity, aging, human immunodeficiency virus type one (HIV-1) infection, and responses to antiretroviral therapy are linked. However, how each factor is linked with the other(s) remains incompletely understood. It has been reported that accelerated aging, advanced HIV-1 infection, inflammation, and host genetic factors are associated with host cellular, mitochondrial, and metabolic alterations. However, the underlying mechanism remains elusive. With these questions in mind, we used chronically HIV-1-infected CD34-NSG humanized mice (hu-mice) to model older people living with HIV and uncover associations between HIV-1 infection and aging. Adult humanized mice were infected with HIV-1 at the age of 20 weeks and maintained for another 40 weeks before sacrifice. Animal brains were collected and subjected to transcriptomics, qPCR, and immunofluorescence assays to uncover immune disease-based biomarkers. CD4+ T cell decline was associated with viral level and age. Upregulated C1QA, CD163, and CXCL16 and downregulated LMNA and CLU were identified as age-associated genes tied to HIV-1 infection. Ingenuity pathway analysis affirmed links to innate immune activation, pyroptosis signaling, neuroinflammation, mitochondrial dysfunction, cellular senescence, and neuronal dysfunction. In summary, CD34-NSG humanized mice are identified as a valuable model for studying HIV-1-associated aging. Biomarkers of immune senescence and neuronal signaling are both age- and virus-associated. By exploring the underlying biological mechanisms that are linked to these biomarkers, interventions for next generation HIV-1-infected patients can be realized.

When ceramides meet immune senescence, a GIMAP5 connection.

When ceramides meet immune senescence, a GIMAP5 connection.

A narrative review on inflammaging and late-onset hypogonadism.

The increasing life expectancy observed in recent years has resulted in a higher prevalence of late-onset hypogonadism (LOH) in older men. LOH is characterized by the decline in testosterone levels and can have significant impacts on physical and mental health. While the underlying causes of LOH are not fully understood, there is a growing interest in exploring the role of inflammaging in its development. Inflammaging is a concept that describes the chronic, low-grade, systemic inflammation that occurs as a result of aging. This inflammatory state has been implicated in the development of various age-related diseases. Several cellular and molecular mechanisms have been identified as contributors to inflammaging, including immune senescence, cellular senescence, autophagy defects, and mitochondrial dysfunction. Despite the extensive research on inflammaging, its relationship with LOH has not yet been thoroughly reviewed in the literature. To address this gap, we aim to review the latest findings related to inflammaging and its impact on the development of LOH. Additionally, we will explore interventions that target inflammaging as potential treatments for LOH.

Growth and longevity modulation through larval environment mediate immunosenescence and immune strategy of Tenebrio molitor

BackgroundThe Disposable Soma Theory of aging suggests a trade-off between energy allocation for growth, reproduction and somatic maintenance, including immunity. While trade-offs between reproduction and immunity are well documented, those involving growth remain under-explored. Rapid growth might deplete resources, reducing investment in maintenance, potentially leading to earlier or faster senescence and a shorter lifespan. However, rapid growth could limit exposure to parasitism before reaching adulthood, decreasing immunity needs. The insect immunity’s components (cellular, enzymatic, and antibacterial) vary in cost, effectiveness, and duration. Despite overall immunity decline (immunosenescence), its components seem to age differently. We hypothesize that investment in these immune components is adjusted based on the resource cost of growth, longevity, and the associated risk of parasitism.ResultsWe tested this hypothesis using the mealworm beetle, Tenebrio molitor as our experimental subject. By manipulating the larval environment, including three different temperatures and three relative humidity levels, we achieved a wide range of growth durations and longevities. Our main focus was on the relationship between growth duration, longevity, and specific immune components: hemocyte count, phenoloxidase activity, and antibacterial activity. We measured these immune parameters both before and after exposing the individuals to a standard bacterial immune challenge, enabling us to assess immune responses. These measurements were taken in both young and older adult beetles. Upon altering growth duration and longevity by modifying larval temperature, we observed a more pronounced investment in cellular and antibacterial defenses among individuals with slow growth and extended lifespans. Intriguingly, slower-growing and long-lived beetles exhibited reduced enzymatic activity. Similar results were found when manipulating larval growth duration and adult longevity through variations in relative humidity, with a particular focus on antibacterial activity.ConclusionThe impact of growth manipulation on immune senescence varies by the specific immune parameter under consideration. Yet, in slow-growing T. molitor, a clear decline in cellular and antibacterial immune responses with age was observed. This decline can be linked to their initially stronger immune response in early life. Furthermore, our study suggests an immune strategy favoring enhanced antibacterial activity among slow-growing and long-lived T. molitor individuals.

Immunological Changes with Age and Innovative Approaches to Bolster Immune Function in Older Adults

Aging is accompanied by a progressive decline in immune function, known as immunosenescence, which renders elderly individuals more susceptible to infections, reduced vaccine efficacy, and increased incidence of autoimmune diseases and cancer. This decline in immunity is characterized by alterations in both innate and adaptive immune responses, including reduced T-cell diversity, impaired function of antigen-presenting cells, and dysregulated cytokine production. Additionally, inflammaging, a chronic low-grade inflammatory state, further contributes to age-related immune dysfunction. Strategies aimed at enhancing immunity in aging individuals have garnered significant attention. Promising interventions include lifestyle modifications encompassing regular exercise, balanced nutrition, and adequate sleep, which can positively impact immune function. Furthermore, vaccination strategies tailored for the elderly, such as high-dose vaccines or adjuvanted formulations, aim to bolster vaccine efficacy. Immunomodulatory therapies, including supplementation with specific micronutrients and pharmacological interventions targeting immune senescence, hold promise for rejuvenating immune responses in older individuals. Understanding the mechanisms underlying immunosenescence and inflammaging is critical in developing targeted approaches to enhance immunity in aging populations. A holistic approach combining lifestyle interventions, vaccination strategies, and innovative immunomodulatory therapies holds potential for mitigating the impact of agerelated immune decline and improving overall healthspan in the elderly. Keywords: Immunosenescence, Aging, Immunity, Inflammaging, Elderly, Immunomodulation, Vaccination Strategies, Immune Rejuvenation, Geriatrics

Accelarated immune ageing is associated with COVID-19 disease severity

BackgroundThe striking increase in COVID-19 severity in older adults provides a clear example of immunesenescence, the age-related remodelling of the immune system. To better characterise the association between convalescent immunesenescence and acute disease severity, we determined the immune phenotype of COVID-19 survivors and non-infected controls.ResultsWe performed detailed immune phenotyping of peripheral blood mononuclear cells isolated from 103 COVID-19 survivors 3–5 months post recovery who were classified as having had severe (n = 56; age 53.12 ± 11.30 years), moderate (n = 32; age 52.28 ± 11.43 years) or mild (n = 15; age 49.67 ± 7.30 years) disease and compared with age and sex-matched healthy adults (n = 59; age 50.49 ± 10.68 years). We assessed a broad range of immune cell phenotypes to generate a composite score, IMM-AGE, to determine the degree of immune senescence. We found increased immunesenescence features in severe COVID-19 survivors compared to controls including: a reduced frequency and number of naïve CD4 and CD8 T cells (p < 0.0001); increased frequency of EMRA CD4 (p < 0.003) and CD8 T cells (p < 0.001); a higher frequency (p < 0.0001) and absolute numbers (p < 0.001) of CD28−ve CD57+ve senescent CD4 and CD8 T cells; higher frequency (p < 0.003) and absolute numbers (p < 0.02) of PD-1 expressing exhausted CD8 T cells; a two-fold increase in Th17 polarisation (p < 0.0001); higher frequency of memory B cells (p < 0.001) and increased frequency (p < 0.0001) and numbers (p < 0.001) of CD57+ve senescent NK cells. As a result, the IMM-AGE score was significantly higher in severe COVID-19 survivors than in controls (p < 0.001). Few differences were seen for those with moderate disease and none for mild disease. Regression analysis revealed the only pre-existing variable influencing the IMM-AGE score was South Asian ethnicity (β\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\beta$$\\end{document} = 0.174, p = 0.043), with a major influence being disease severity (β\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\beta$$\\end{document} = 0.188, p = 0.01). ConclusionsOur analyses reveal a state of enhanced immune ageing in survivors of severe COVID-19 and suggest this could be related to SARS-Cov-2 infection. Our data support the rationale for trials of anti-immune ageing interventions for improving clinical outcomes in these patients with severe disease.

Higher temperature accelerates the aging-dependent weakening of the melanization immune response in mosquitoes.

The body temperature of mosquitoes, like most insects, is dictated by the environmental temperature. Climate change is increasing the body temperature of insects and thereby altering physiological processes such as immune proficiency. Aging also alters insect physiology, resulting in the weakening of the immune system in a process called senescence. Although both temperature and aging independently affect the immune system, it is unknown whether temperature alters the rate of immune senescence. Here, we evaluated the independent and combined effects of temperature (27°C, 30°C and 32°C) and aging (1, 5, 10 and 15 days old) on the melanization immune response of the adult female mosquito, Anopheles gambiae. Using a spectrophotometric assay that measures phenoloxidase activity (a rate limiting enzyme) in hemolymph, and therefore, the melanization potential of the mosquito, we discovered that the strength of melanization decreases with higher temperature, aging, and infection. Moreover, when the temperature is higher, the aging-dependent decline in melanization begins at a younger age. Using an optical assay that measures melanin deposition on the abdominal wall and in the periostial regions of the heart, we found that melanin is deposited after infection, that this deposition decreases with aging, and that this aging-dependent decline is accelerated by higher temperature. This study demonstrates that higher temperature accelerates immune senescence in mosquitoes, with higher temperature uncoupling physiological age from chronological age. These findings highlight the importance of investigating the consequences of climate change on how disease transmission by mosquitoes is affected by aging.

Effects of immune exhaustion and senescence of innate immunity in autoimmune disorders.

Innate immune system activation is crucial in the inflammatory response, but uncontrolled activation can lead to autoimmune diseases. Cellular exhaustion and senescence are two processes that contribute to innate immune tolerance breakdown. Exhausted immune cells are unable to respond adequately to specific antigens or stimuli, while senescent cells have impaired DNA replication and metabolic changes. These processes can impair immune system function and disrupt homeostasis, leading to the emergence of autoimmunity. However, the influence of innate immune exhaustion and senescence on autoimmune disorders is not well understood. This review aims to describe the current findings on the role of innate immune exhaustion and senescence in autoimmunity, focusing on the cellular and molecular changes involved in each process. Specifically, the article explores the markers and pathways associated with immune exhaustion, such as PD-1 and TIM-3, and senescence, including Β-galactosidase (β-GAL), lamin B1, and p16ink4a, and their impact on autoimmune diseases, namely type 1 diabetes, rheumatoid arthritis, systemic lupus erythematosus, and immune-mediated myopathies. Understanding the mechanisms underlying innate immune exhaustion and senescence in autoimmunity may provide insights for the development of novel therapeutic strategies.

Incomplete recovery of the CD4+/CD8+ ratio is associated with the late introduction of antiretroviral therapy among people living with HIV infection.

Despite being subject to lower AIDS-related mortality rates and having a higher life expectancy, patients with HIV are more prone to develop non-AIDS events. A low CD4+/CD8+ ratio during antiretroviral therapy identifies people with heightened immune senescence and increased risk of mortality. In clinical practice, finding determinants of a low CD4+/CD8+ ratio may be useful for identifying patients who require close monitoring due to an increased risk of comorbidities and death. We performed a prospective study on the evolution of the CD4+/CD8+ ratio in 60 patients infected with HIV (80% males), who were subjected to two different antiretroviral regimens: early and deferred therapy. The initial CD4+/CD8+ ratio was ≤1 for 70% of the patients in both groups. Older age, CD4+ cell count at inclusion, Nadir CD8+T-cell count, and Initial CD4+/CD8+ ratio ≤ 1 were risk factors for lack of ratio recovery. In the multivariate analysis, a CD4+/CD8+ ratio > 1 at the start of the treatment was found to be a determinant factor in maintaining a CD4+/CD8+ ratio > 1. The nadir CD4+T-cell count was lower in the deferred therapy group (p=0.004), and the last CD4+/CD8+ ratio ≤1 was not associated with comorbidities. Ratio recovery was not associated with the duration of HIV infection, time without therapy, or absence of AIDS incidence. A greater improvement was observed in patients treated early (p=0.003). In contrast, the slope of increase was slower in patients who deferred treatment. In conclusion, the increase in the CD4+/CD8+ ratio occurred mostly for patients undergoing early strategy treatment and its extension did not seem to be related to previous HIV-related factors.

PD-1 expression in tumor infiltrating lymphocytes as a prognostic marker in early-stage non-small cell lung cancer.

Programmed death ligand - 1 (PD-L1) expression is a well-established predictive biomarker for immunotherapy in non-small cell lung cancer (NSCLC). Programmed death - 1 (PD-1) serves as the target protein to PD-L1 and their interaction serves as a crucial pathway for immune evasion. This study aimed to investigate the expression pattern of PD-1 on Tumor-infiltrating lymphocytes (TILs) in early-stage NSCLC, and its potential role as prognostic biomarker. PD-1 was evaluated in 474 surgical resected early-stage NSCLC specimens, using Tissue microarray and immunohistochemical staining. Expression was scored as negative (<1%) or positive. Positive PD-1 expression was further divided into low (<10%) and high (≥10%). None of the patients had received treatment with PD-1/PD-L1 inhibitors. PD-1 expression ≥1% in TILs was observed in 83.5% of cases and was associated with pT stage (p=0.02), grade 3 (p=0.004), and adenocarcinoma subtype (p=0.05). Individuals with high PD-1 expression (≥10%) experienced reduced 10-year overall survival (Log-Rank test = 0.005). In addition, high PD-1 expression emerged as an independent factor associated with reduced survival on multivariate analysis (HR: 1.328 (95% CI: 1.074-1.641). Patients with early-stage NSCLC who exhibited PD-1 expression of ≥10% on TILs had an unfavorable 10-year OS rate. These findings indicate that elevated PD-1 expression on TILs can be associated with immune evasion during the early stages of malignancy evolution in the NSCLC setting and further research is required to further delineate the role of PD-1/PD-L1 pathway on tumor immune senescence. These results underline the potential role of PD-1/PD-L1 inhibitors in the treatment of early-stage NSCLC.

Linking alcohol use to Alzheimer’s disease: Interactions with aging and APOE along immune pathways

Although it is known that APOE genotype is the strongest genetic risk factor for late-onset Alzheimer’s disease (AD), AD development is a multifactorial process. Alcohol use is a contributor to the epidemic of AD and related dementias in the US and globally, yet mechanisms are not fully understood. Carriers of the APOE ε4 allele show elevated risk of dementia in relation to several lifestyle factors, including alcohol use. In this review, we describe how alcohol interacts with APOE genotype and aging with potential implications for AD promotion. Age-related immune senescence and “inflammaging” (i.e., low-grade inflammation associated with aging) are increasingly recognized as contributors to age-related disease. We focus on three immune pathways that are likely contributors to AD development, centering on alcohol and APOE genotype interactions, specifically: 1) microbial translocation and immune activation, 2) the senescence associated secretory phenotype (SASP), and 3) neuroinflammation. First, microbial translocation, the unphysiological movement of gut products into systemic circulation, elicits a proinflammatory response and increases with aging, with proposed links to AD. Second, the SASP is a set of intercellular signaling factors, e.g., proinflammatory cytokines and chemokines, growth regulators, and proteases, that drives cellular aging when senescent cells remain metabolically active. The SASP can drive development of aging-diseases such as AD. Third, neuroinflammation occurs via numerous mechanisms such as microglial activation and is gaining recognition as an etiological factor in the development of AD. This review focuses on interactions of alcohol with APOE genotype and aging along these three pathways that may promote AD. Further research on these processes may inform development of strategies to prevent onset and progression of AD and to delay associated cognitive decline.

AGING-RELATED IMMUNE CELLS PHENOTYPES AND ALL-CAUSE MORTALITY IN THE FRAMINGHAM HEART STUDY

Abstract Almost 2 billion people will likely be above the age of 60 by 2050. Aging is a process that is intrinsically complicated. One of the measures for immune system senescence is aging related immune cells phenotypes (ARIP)s. Besides CD8/CD4 ratio, new immunosenescence phenotypes have been proposed. The associations between ARIPs and all-cause mortality during long-term follow up is understudied. We profiled immune cells using flow cytometry and prospectively investigated ten different ARIPs, namely, CD4+CD27-, CD4+CD28-CD27-, CD8+CD27-, CD8+CD28-CD27-, CD4+/CD8+ ratio, CD4+(Tnaive/(T Central Memory (Tcm)+T Effector Memory (Tem)+T Effector (Teff)), CD8+ (Tnaive/(Tcm+Tem+Teff)), Granzyme B+CD8/Granzyme B+CD4 ratio, CD8+ Tc17/Treg ratio and CD4+ Th17/Treg ratio in relation to survival outcome among 990 dementia-free Framingham Heart Study (FHS) Offspring cohort participants who attended the seventh exam (1998-2001, mean age 62 years, range 40-88, 52% female). Cox proportional hazards regression models adjusting for age and sex with robust variance to account for family correlation were used to test for association between the ARIPs and hazard of death. During up to 20 years of follow up, the survival rate was 66%. Higher CD8+ Tc17/Treg ratio was significantly associated with better survival (HR:0.82 [0.7-0.94], p&amp;lt; 0.001). Higher CD4+ Th17/Treg ratio and CD4/CD8 ratio were also nominally associated with lower risk of death (HR:0.87, [0.75-0.97], p=0.01 and HR 0.9, [0.79-0.99], p=0.04, respectively). Other ARIPs were unassociated with all-cause mortality. We conclude that further investigation of the CD8+Tc17/Treg and CD4+ Th17/Treg ratios as ARIP biomarkers for risk of all-cause mortality is justified.

Metabolic pathways in immune senescence and inflammaging: Novel therapeutic strategy for chronic inflammatory lung diseases. An EAACI position paper from the Task Force for Immunopharmacology.

The accumulation of senescent cells drives inflammaging and increases morbidity of chronic inflammatory lung diseases. Immune responses are built upon dynamic changes in cell metabolism that supply energy and substrates for cell proliferation, differentiation, and activation. Metabolic changes imposed by environmental stress and inflammation on immune cells and tissue microenvironment are thus chiefly involved in the pathophysiology of allergic and other immune-driven diseases. Altered cell metabolism is also a hallmark of cell senescence, a condition characterized by loss of proliferative activity in cells that remain metabolically active. Accelerated senescence can be triggered by acute or chronic stress and inflammatory responses. In contrast, replicative senescence occurs as part of the physiological aging process and has protective roles in cancer surveillance and wound healing. Importantly, cell senescence can also change or hamper response to diverse therapeutic treatments. Understanding the metabolic pathways of senescence in immune and structural cells is therefore critical to detect, prevent, or revert detrimental aspects of senescence-related immunopathology, by developing specific diagnostics and targeted therapies. In this paper, we review the main changes and metabolic alterations occurring in senescent immune cells (macrophages, B cells, T cells). Subsequently, we present the metabolic footprints described in translational studies in patients with chronic asthma and chronic obstructive pulmonary disease (COPD), and review the ongoing preclinical studies and clinical trials of therapeutic approaches aiming at targeting metabolic pathways to antagonize pathological senescence. Because this is a recently emerging field in allergy and clinical immunology, a better understanding of the metabolic profile of the complex landscape of cell senescence is needed. The progress achieved so far is already providing opportunities for new therapies, as well as for strategies aimed at disease prevention and supporting healthy aging.

After the COVID-19 pandemic-Which new vaccinations for adults are available or coming soon?

The accumulation of respiratory infections in the winter months repeatedly highlights the relevance of prevention through vaccination, even beyond apandemic. Current developments in this field are therefore highly relevant, particularly for older people who are more susceptible to infections due to immune senescence and comorbidities. The Standing Committee on Vaccination (STIKO) has responded accordingly by recommending the 20-valent pneumococcal conjugate vaccine PCV20 for standard and indication vaccination of adults. Furthermore, new vaccines against respiratory syncytial virus (RSV) infections are available for which the STIKO has not yet issued arecommendation. The development of other more effective and more immunogenic vac2cines is being driven in particular by new technologies, such as mRNA or vector vaccines. Various higher valent pneumococcal vaccine candidates and, for example, universal influenza vaccines are also already in development.

Investigation of inflammation in Lewy body dementia: a scoping review

AbstractBackgroundInflammatory mechanisms are increasingly recognized as part of the pathogenesis of neurodegenerative diseases, including Lewy body dementia (LBD). Advances in analytical techniques using in vivo and postmortem samples have been applied to address questions of key mechanisms and relevance to clinical manifestations. Our primary objective was to review methods used to investigate inflammation in LBD (dementia with Lewy bodies and Parkinson’s disease dementia), and how these are applied to conceptualise inflammation. Our secondary objective was to identify alterations in inflammatory signals in LBD compared to people without neurodegenerative disease, and compared to related neurodegenerative disease, in particular AD and PD.MethodA scoping review was performed by identifying relevant human studies that investigated inflammation in LBD. The major electronic databases MEDLINE, Embase, Web of Science, and PSYCHInfo were searched. Two authors performed abstract screening and full text review.ResultOf 1970 results screened, 65 studies were included. Twenty‐nine studies analysed postmortem brain tissue and 35 included living subjects. Largely cross‐sectional data were available, although 2 longitudinal clinical studies of prodromal Lewy body disease were noted. Analysis of biofluid (blood and cerebrospinal fluid) was the most common in vivo method used (n = 31) and 3 studies investigated LBD genetics. Investigations were focused on inflammatory immune cell activity (microglia, astrocytes, lymphocytes), and molecules linked to inflammation (e.g., cytokines). Results of included studies supported innate and adaptive immune system contribution to inflammation associated with Lewy body pathology and clinical features of the disease. Different signals in early and late‐stage disease, with possible late immune senescence including dystrophic microglia and altered adaptive immunity, were distinct from Alzheimer’s disease. The strength of these associations is limited by the varying methodologies, small study sizes and cross‐sectional nature of data.ConclusionCurrent investigation of inflammation in LBD utilises substrate collected from early to late‐stage disease. Strengths and limitations of the range of analytical techniques used must be considered when forming conclusions. Longitudinal data that informs associations with clinical and other biomarker outcomes is needed to improve understanding of inflammatory activity over the disease course of LBD. This could identify markers of disease activity and therapeutic targets.

Vaccination in old age: an overview

Vaccinations against infectious diseases are ahighly effective preventive measure, especially in old age due to the higher susceptibility to infections. As the effectiveness of vaccinations decreases in old age due to immune senescence but also due to comorbidities, specific, more immunogenic vaccines have been developed for this target group. In Germany, the Standing Commission on Vaccination (STIKO) publishes annually updated vaccination recommendations also specifically for the 60+ years age group. Since 2018, standard vaccinations for this group have included herpes zoster vaccination with adjuvanted inactivated vaccine. Since 2021, the use of the quadrivalent influenza high-dose vaccine is recommended for this age group. Currently, the annual COVID-19 vaccination and the single pneumococcal vaccination with the new 20-valent conjugate vaccine have been added as standard vaccinations. The free STIKO app provides an always up to date overview of standard and indicated vaccinations for all age groups.