scholarly journals STING SNP R293Q Is Associated with a Decreased Risk of Aging-Related Diseases

Gerontology ◽  
2018 ◽  
Vol 65 (2) ◽  
pp. 145-154 ◽  
Author(s):  
Lutz Hamann ◽  
Juan S. Ruiz-Moreno ◽  
Malgorzata Szwed ◽  
Malgorzata Mossakowska ◽  
Linn Lundvall ◽  
...  
Keyword(s):  
Cell Death ◽  
Immune System ◽  
Bacterial Infections ◽  
Healthy Aging ◽  
The Elderly ◽  
Innate Immune ◽  
Low Grade ◽  
Associated Diseases ◽  
Chronic Lung Diseases ◽  
Sting Pathway

Background: Aging is a multifactorial process driven by several conditions. Among them, inflamm-aging is characterized by chronic low-grade inflammation driving aging-related diseases. The aged immune system is characterized by the senescence-associated secretory phenotype, resulting in the release of proinflammatory cytokines contributing to inflamm-aging. Another possible mechanism resulting in inflamm-aging could be the increased release of danger- associated molecular patterns (DAMPs) by increased cell death in the elderly, leading to a chronic low-grade inflammatory response. Several pattern recognition receptors of the innate immune system are involved in recognition of DAMPs. The DNA-sensing cGAS-STING pathway plays a pivotal role in combating viral and bacterial infections and recognizes DNA released by cell death during the process of aging, which in turn may result in increased inflamm-aging. Objective: The aim of this study was to investigate whether a variation within the STING gene with known impaired function may be associated with protection from aging-related diseases by decreasing the process of inflamm-aging. Methods: STING (Tmem173) R293Q was genotyped in a cohort of 3,397 aged subjects (65–103 years). The distribution of the variant allele in healthy subjects and subjects suffering from aging-associated diseases was compared by logistic regression analysis. Results: We show here that STING 293Q allele carriers were protected from aging-associated diseases (OR = 0.823, p = 0.038). This effect was much stronger in the subgroup of subjects suffering from chronic lung diseases (OR = 0.730, p = 0.009). Conclusion: Our results indicate that decreased sensitivity of the innate immune receptors is associated with healthy aging, most likely due to a decreased process of inflamm-aging.

scholarly journals Some of the Immunogenetics Aspects of Aging

2021 ◽  
Vol 14 (1) ◽  
pp. 16-30
Author(s):  
Bushra N. Al Hadra
Keyword(s):  
Immune System ◽  
Autoimmune Diseases ◽  
Healthy Aging ◽  
Human Life ◽  
Major Gene ◽  
Positive Association ◽  
The Elderly ◽  
Low Grade ◽  
Cell Repertoire ◽  
Anti Inflammatory

Summary The human life span could be influenced by the combined effect of environment, lifestyle, and genetic factors. Twin and family studies suggest that our genes control up to 25% of the lifespan. The aging immune system undergoes age-associated changes at multiple levels, resulting in a gradual loss of its ability to protect the organism against infections, low vaccine responses, and an increased probability of developing autoimmune diseases and malignancies. The highly polymorphic HLA complex is one of the major gene candidates associated with aging due to its crucial role in developing adaptive immunity and protecting the organism. Most of the data available have so far demonstrated a positive association with healthy aging for HLA alleles/haplotypes as protective against malignancies, autoimmune diseases, and conferring better control and response to infections. One of aging’s main manifestations is the chronic, low-grade inflammatory state observed in older people, caused by an imbalance between pro- and anti-inflammatory cytokines. In general, it is has been agreed that longevity is related to anti-inflammatory genotype profiles. With advanced age, changes also occur in the B cell repertoire, which significantly affects the humoral immunity and leads to inadequate responses to infections and vaccines in the elderly. New genetic biomarkers associated with aging are being explored and discovered, contributing to a better understanding of the molecular processes underlying the immune dysfunction related to aging and developing strategies for rejuvenating the immune system based on immune-risk phenotypes.

scholarly journals NK Cells in Healthy Aging and Age-Associated Diseases

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Xavier Camous ◽  
Alejandra Pera ◽  
Rafael Solana ◽  
Anis Larbi
Keyword(s):  
Immune System ◽  
Nk Cells ◽  
Immune Cells ◽  
Healthy Aging ◽  
Elderly Population ◽  
Nk Cell ◽  
The Elderly ◽  
Deep Impact ◽  
Cell Functions ◽  
Associated Diseases

NK cells exhibit the highest cytotoxic capacity within the immune system. Alteration of their number or functionality may have a deep impact on overall immunity. This is of particular relevance in aging where the elderly population becomes more susceptible to infection, cancer, autoimmune diseases, and neurodegenerative diseases amongst others. As the fraction of elderly increases worldwide, it becomes urgent to better understand the aging of the immune system to prevent and cure the elderly population. For this, a better understanding of the function and phenotype of the different immune cells and their subsets is necessary. We review here NK cell functions and phenotype in healthy aging as well as in various age-associated diseases.

scholarly journals Immunological aging and clinical consequences

2020 ◽  
Vol 74 ◽  
pp. 260-271
Author(s):  
Anna Tylutka ◽  
Agnieszka Zembroń-Łacny
Keyword(s):  
Immune System ◽  
Bacterial Infections ◽  
The Elderly ◽  
Interferon Γ ◽  
Immune Risk Profile ◽  
Increased Risk ◽  
Tnf Α ◽  
Insufficient Response ◽  
Clinical Consequences ◽  
Exacerbation Of Symptoms

Immunosenescence is defined as the changes in the immune system associated with age. It is a progressive and irreversible process involving a decrease in the number of naïve T and B cells, NK cells cytotoxic and activity, and disruption of pro and anti-inflammatory balance by altering the production of IL-2, -4, -6, -10, -10, TNF-α, interferon γ and others. With age there is an increase in autoimmunity and generalized inflammation with simultaneous immunodeficiency, which results in greater susceptibility to infectious diseases, a decrease in reactivity to prophylactic vaccinations, the incidence of autoimmune diseases, and increased risk of infectious injury complications, exacerbation of symptoms of chronic diseases and an insufficient response to the presence of cells cancer. For years, based on the analysis of the frequency of viral and bacterial infections, immunological indicators and inflammation, attempts have been made to develop the immune risk profile (IRP) and effective methods of preventing disorders of the immune system and prolonging the functional capacity of the elderly.

scholarly journals Resistance training and immunosenescence of the innate immune system

2019 ◽  
Vol 0 (Avance Online) ◽  
Author(s):  
João Bartholomeu-Neto ◽  
David Junger F Alves ◽  
Ciro José Brito ◽  
Aparecido Pimentel Ferreira ◽  
Otávio de Toledo Nóbrega ◽  
...  
Keyword(s):  
Immune System ◽  
Resistance Training ◽  
Innate Immune System ◽  
The Elderly ◽  
Innate Immune ◽  
Phagocytic Cells ◽  
Phagocytic Capacity ◽  
Functional Aspects ◽  
Increased Risk ◽  
Effects Of Aging

Phagocytic cells constitute the first defense line against the diversity of infectious agents. The effects of aging on the immune function – immunosenescence – affect the phagocytic capacity of neutrophils and monocytes/macrophages and result in increased risk to cancer and other diseases. The aim of this review was to assess the functional aspects of the innate system cells in aging. Evidence brought about by this review suggests that resistance training is a useful therapy to mitigate the adverse effects of the innate immune system aging process. Resistance training is consistently recommended as assistent strategy for prevention of the inflamaging and associated chronic diseases, but establishing adequate program is still in demand. In addition, future studies are needed to improve our understanding of the resistance training-induced mechanisms underlying changes in phagocytic activity in the elderly. Resumen Las células fagocíticas constituyen la primera línea de defensa contra los agentes infecciosos. Los efectos del envejecimiento sobre la función inmune – inmunosenescencia – afectan la capacidad fagocítica de neutrófilos y monocitos/macrófagos y resultan en riesgo aumentado para el cáncer y otras enfermedades. El objetivo de esta revisión fue evaluar los aspectos funcionales de las células del sistema innato en el envejecimiento. Las evidencias revisadas sugieren que el entrenamiento de resistencia es una terapia útil para atenuar los efectos adversos del proceso de envejecimiento del sistema inmune innato. Se recomienda el entrenamiento de resistencia continuamente como estrategia complementaria para la prevención de la inflamación y de las enfermedades crónicas asociadas, pero hay que establecer el programa adecuado. Además, se necesitan más investigaciones para mejorar nuestra comprensión de los mecanismos modulados por el entrenamiento de resistencia que inducen a los cambios en la actividad fagocítica en las personas mayores. Resumo As células fagocitárias constituem a primeira linha de defesa contra agentes infecciosos. Os efeitos do envelhecimento sobre a função imune – imunossenescência – afetam a capacidade fagocítica de neutrófilos e monócitos/macrófagos e resultam em aumento do risco para câncer e outras doenças. O objetivo desta revisão foi avaliar os aspectos funcionais das células do sistema inato durante o envelhecimento. Os estudos revisados sugerem que o treinamento resistido é uma terapia útil para atenuar os efeitos adversos do processo de envelhecimento do sistema imune inato. Recomenda-se que o treinamento resistido seja aplicado continuamente como estratégia complementar para a prevenção da inflamação e doenças crônicas associadas, porém deve-se estabelecer o programa adequado. Ressalta-se ainda que, são necessários mais estudos para melhorar a compreensão sobre os mecanismos modulados pelo treinamento resistido que induzem a alterações na atividade fagocítica em idosos.

scholarly journals Attenuation of cGAS/STING activity during mitosis

2020 ◽  
Vol 3 (9) ◽  
pp. e201900636 ◽  
Author(s):  
Brittany L Uhlorn ◽  
Eduardo R Gamez ◽  
Shuaizhi Li ◽  
Samuel K Campos
Keyword(s):  
Immune System ◽  
Innate Immune System ◽  
Cellular Stress ◽  
Innate Immune ◽  
Regulatory Mechanisms ◽  
Mitotic Chromosomes ◽  
Interphase Cells ◽  
Microbial Infections ◽  
Foreign Dna ◽  
Sting Pathway

The innate immune system recognizes cytosolic DNA associated with microbial infections and cellular stress via the cGAS/STING pathway, leading to activation of phospho-IRF3 and downstream IFN-I and senescence responses. To prevent hyperactivation, cGAS/STING is presumed to be nonresponsive to chromosomal self-DNA during open mitosis, although specific regulatory mechanisms are lacking. Given a role for the Golgi in STING activation, we investigated the state of the cGAS/STING pathway in interphase cells with artificially vesiculated Golgi and in cells arrested in mitosis. We find that whereas cGAS activity is impaired through interaction with mitotic chromosomes, Golgi integrity has little effect on the enzyme’s production of cGAMP. In contrast, STING activation in response to either foreign DNA (cGAS-dependent) or exogenous cGAMP is impaired by a vesiculated Golgi. Overall, our data suggest a secondary means for cells to limit potentially harmful cGAS/STING responses during open mitosis via natural Golgi vesiculation.

HIV infection and aging of the innate immune system

Sexual Health ◽  
2011 ◽  
Vol 8 (4) ◽  
pp. 453 ◽  
Author(s):  
Anna C. Hearps ◽  
Thomas A. Angelovich ◽  
Anthony Jaworowski ◽  
John Mills ◽  
Alan L. Landay ◽  
...  
Keyword(s):  
Immune System ◽  
Hiv Infection ◽  
Immune Cells ◽  
Inflammatory Diseases ◽  
The Elderly ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Telomere Attrition ◽  
Age Related ◽  
The Impact

The increased life expectancy of HIV-infected individuals due to improved treatment has revealed an unexpected increase in non-AIDS comorbidities that are typically associated with older age including cardiovascular disease, dementia and frailty. The majority of these diseases arise as the result of dysregulated systemic inflammation, and both the aged and HIV-infected individuals exhibit elevated basal levels of inflammation. In the elderly, increased inflammation and age-related diseases are associated with a state of impaired immunity called immunosenescence, which is thought to result from a lifetime of immune stimulation. It is now apparent that HIV induces premature immunosenescence within T-cells; however, the impact of HIV on aging of cells of the innate arm of the immune system is unknown. Innate immune cells play a central role in inflammation and are thus critical for the pathogenesis of inflammatory diseases. Limited evidence suggests HIV infection mimics age-related changes to innate immune cells; however, the extent of this effect and the mechanism underlying these changes remain to be defined. This review focuses on the impact of HIV infection on the function and aging of innate immune cells and discusses potential drivers of premature immunosenescence including chronic endotoxaemia, residual viraemia, telomere attrition and altered cellular signalling.

scholarly journals Vitamin D and inflammation in the prevention of type 2 diabetes: public health relevance

2012 ◽  
Vol 3 (4) ◽  
pp. 243
Author(s):  
Alaa Badawi ◽  
Eman Sadoun ◽  
Mohamed H. Al Thani
Keyword(s):  
Public Health ◽  
Type 2 Diabetes ◽  
Vitamin D ◽  
Immune System ◽  
Innate Immune System ◽  
Population Level ◽  
Innate Immune ◽  
Low Grade ◽  
Low Grade Inflammation

The incidence of type 2 diabetes mellitus (T2DM) is increasing worldwide. To reduce the disease risk and burden at the population level, preventative strategies should be developed with minimal cost and effort and with no side-effects. Low-grade inflammation resulting from imbalances in the innate immune system has been associated with an array of chronic disorders that predispose to the later development of T2DM (e.g., obesity, metabolic syndrome, and insulin resistance). As a result, inflammation may contribute to the pathogenesis of T2DM. Therefore, attenuation of this inflammatory response via modulating the innate immune system could lead to improved insulin sensitivity and delayed disease onset. Dietary supplementation with vitamin D may represent a novel strategy toward the prevention and control of T2DM at the population level due to its anti-inflammatory and antioxidant properties. This review examines current knowledge linking T2DM to chronic low-grade inflammation and the role of vitamin D in modulating this relationship. The concept that vitamin D, via attenuating inflammation, could be employed as a novel preventive measure for T2DM is evaluated in the context of its relevance to health care and public health practices.

scholarly journals Role of Innate Immunity in Initiation and Progression of Osteoarthritis, with Emphasis on Horses

Animals ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 3247
Author(s):  
Juan Estrada McDermott ◽  
Lynn Pezzanite ◽  
Laurie Goodrich ◽  
Kelly Santangelo ◽  
Lyndah Chow ◽  
...  
Keyword(s):  
Immune System ◽  
Innate Immune System ◽  
Companion Animals ◽  
Disease Process ◽  
Joint Inflammation ◽  
Innate Immune ◽  
Low Grade ◽  
Acute Trauma ◽  
Low Grade Inflammation

Osteoarthritis (OA) is a common condition with diverse etiologies, affecting horses, humans, and companion animals. Importantly, OA is not a single disease, but rather a disease process initiated by different events, including acute trauma, irregular or repetitive overload of articular structures, and spontaneous development with aging. Our understanding of the pathogenesis of OA is still evolving, and OA is increasingly considered a multifactorial disease in which the innate immune system plays a key role in regulating and perpetuating low-grade inflammation, resulting in sustained cartilage injury and destruction. Macrophages within the synovium and synovial fluid are considered the key regulators of immune processes in OA and are capable of both stimulating and suppressing joint inflammation, by responding to local and systemic cues. The purpose of this review is to examine the role of the innate immune system in the overall pathogenesis of OA, drawing on insights from studies in humans, animal models of OA, and from clinical and research studies in horses. This review also discusses the various therapeutic immune modulatory options currently available for managing OA and their mechanisms of action.

The Innate Immune System Favors Emergency Monopoiesis at the Expense of DC Differentiation to Control Bacterial Infections

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2722-2722
Author(s):  
Kristin Bieber ◽  
Karina A. Pasquevich ◽  
Manina Günter ◽  
Matthias Grauer ◽  
Oliver Pötz ◽  
...  
Keyword(s):  
Immune System ◽  
Bacterial Infection ◽  
Bacterial Infections ◽  
Conflicts Of Interest ◽  
Bacterial Load ◽  
Innate Immune ◽  
General Response ◽  
The Impact ◽  
Myeloid Progenitors

Abstract Dendritic cells (DCs) are critical in host defense against infection, bridging the innate and adaptive immune system. Patients with sepsis display reduced circulating and splenic DCs and impaired DC function that may contribute to prolonged immune suppression and exacerbation of infection. However, the mechanisms of pathogen-induced DC depletion remain poorly understood. Here, a mouse model of systemic bacterial infection was employed to analyze the impact of different bacterial pathogens on DC development in vivo. We found that the numbers of bone marrow (BM) hematopoietic progenitors committed to the DC lineages were reduced following systemic infection with different Gram-positive and Gram-negative bacteria. In parallel, a TLR4-dependent increase of committed monocyte progenitors in the BM as well as mature monocytes in the spleen was observed. In line, adoptively transferred FLT3+ myeloid progenitors (MPs) developed preferentially to monocytes at the expense of DCs in infected animals. Analyses performed on mixed BM chimeras suggested that both the reduction of DC progenitors and the induction of monopoiesis following infection were dependent on extrinsic TLR4 signaling driving the secretion of IFN-g regulated chemokines. Consistently, these effects were completely abrogated by suppression of IFN-g signaling. Elevated monocyte numbers in the spleen triggered by infection were due to a CCR2-dependent egress from the BM. In CCR2-deficient mice, in which monocytosis reportedly is abrogated, we observed a significantly increased bacterial load in the spleen and a reduced survival rate, highlighting the importance of monocytes for bacterial clearance. Together, our data provide evidence for a general response of myeloid progenitors upon bacterial infection to enhance monocyte production, thereby increasing the availability of innate immune cells as a first line of defense against invading pathogens. Concomitantly the development of DCs is impaired, which may be responsible for transient immunosuppression in e.g. bacterial sepsis. Disclosures No relevant conflicts of interest to declare.

scholarly journals Proteomic Analysis of Low-Grade, Early-Stage Endometrial Carcinoma Reveals New Dysregulated Pathways Associated with Cell Death and Cell Signaling

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 794
Author(s):  
Álvaro López-Janeiro ◽  
Ignacio Ruz-Caracuel ◽  
Jorge L. Ramón-Patino ◽  
Vivian De Los Ríos ◽  
María Villalba Esparza ◽  
...  
Keyword(s):  
Immune Response ◽  
Cell Death ◽  
Cell Signaling ◽  
Endometrial Carcinoma ◽  
Proteomic Analysis ◽  
Early Stage ◽  
Innate Immune ◽  
Future Research ◽  
Low Grade

Low-grade, early-stage endometrial carcinoma (EC) is the most frequent malignant tumor of the uterine corpus. However, the molecular alterations that underlie these tumors are far from being fully understood. The purpose of this study is to describe dysregulated molecular pathways from EC patients. Sixteen samples of tumor tissue and paired healthy controls were collected and both were subjected to mass spectrometry (MS)/MS proteomic analysis. Gene ontology and pathway analysis was performed to discover dysregulated pathways and/or proteins using different databases and bioinformatic tools. Dysregulated pathways were cross-validated in an independent external cohort. Cell signaling, immune response, and cell death-associated pathways were robustly identified. The SLIT/ROBO signaling pathway demonstrated dysregulation at the proteomic and transcriptomic level. Necroptosis and ferroptosis were cell death-associated processes aberrantly regulated, in addition to apoptosis. Immune response-associated pathways showed a dominance of innate immune responses. Tumor immune infiltrates measured by immunofluorescence demonstrated diverse lymphoid and myeloid populations. Our results suggest a role of SLIT/ROBO, necroptosis, and ferroptosis, as well as a prominent role of innate immune response in low-grade, early-stage EC. These results could guide future research in this group of tumors.

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