Alterations of monocyte NF-κB p65/RelA signaling in a cohort of older medical patients, age-matched controls, and healthy young adults

Tavenier, Juliette; Rasmussen, Line Jee Hartmann; Houlind, Morten Baltzer; Andersen, Aino Leegaard; Panum, Inge; Andersen, Ove; Petersen, Janne; Langkilde, Anne; Nehlin, Jan O.

doi:10.1186/s12979-020-00197-7

Cited by 23 publications

(15 citation statements)

References 65 publications

(101 reference statements)

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“…Given that high suPAR is associated with a lower effectiveness of the immune system, as illustrated by the elevated risk of disease progression and adverse events, as well as its associations with inflammation and multiple indicators of accelerated aging and functional decline, suPAR may be a useful biomarker of SCI that can be used to quantify the level of inflammaging and immunosenescence. In support of this, we recently reported elevated suPAR levels in a patient population characterized by accelerated aging and multiple signs of immunosenescence, including reduced capacity to respond to immune stimulation, defects in NF-κB signaling, and higher levels of inflammatory biomarkers (CRP, IL-6, IL-18, TNFα, growth differentiation factor 15 [GDF15]) and NLRP3 inflammasome expression compared to age-matched and young healthy controls ( 183 ).…”

Section: Discussionmentioning

confidence: 74%

Soluble Urokinase Plasminogen Activator Receptor (suPAR) as a Biomarker of Systemic Chronic Inflammation

2021

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Systemic chronic inflammation (SCI) is persistent, health-damaging, low-grade inflammation that plays a major role in immunosenescence and in development and progression of many diseases. But currently, there are no recognized standard biomarkers to assess SCI levels alone, and SCI is typically measured by combining biomarkers of acute inflammation and infection, e.g., CRP, IL-6, and TNFα. In this review, we highlight 10 properties and characteristics that are shared by the blood protein soluble urokinase plasminogen activator receptor (suPAR) and SCI, supporting the argument that suPAR is a biomarker of SCI: (1) Expression and release of suPAR is upregulated by immune activation; (2) uPAR and suPAR exert pro-inflammatory functions; (3) suPAR is associated with the amount of circulating immune cells; (4) Blood suPAR levels correlate with the levels of established inflammatory biomarkers; (5) suPAR is minimally affected by acute changes and short-term influences, in contrast to many currently used markers of systemic inflammation; (6) Like SCI, suPAR is non-specifically associated with multiple diseases; (7) suPAR and SCI both predict morbidity and mortality; (8) suPAR and SCI share the same risk factors; (9) suPAR is associated with risk factors and outcomes of inflammation above and beyond other inflammatory biomarkers; (10) The suPAR level can be reduced by anti-inflammatory interventions and treatment of disease. Assessing SCI has the potential to inform risk for morbidity and mortality. Blood suPAR is a newer biomarker which may, in fact, be a biomarker of SCI since it is stably associated with inflammation and immune activation; shares the same risk factors as many age-related diseases; is both elevated by and predicts age-related diseases. There is strong evidence that suPAR is a prognostic marker of adverse events, morbidity, and mortality. It is associated with immune activity and prognosis across diverse conditions, including kidney disease, cardiovascular disease, cancer, diabetes, and inflammatory disorders. Thus, we think it likely represents a common underlying disease-process shared by many diseases; that is, SCI. We review the supporting literature and propose a research agenda that can help test the hypothesis that suPAR indexes SCI, with the potential of becoming the new gold standard for measuring SCI.

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Section: Discussionmentioning

confidence: 74%

Soluble Urokinase Plasminogen Activator Receptor (suPAR) as a Biomarker of Systemic Chronic Inflammation

2021

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“…Activation of the NF-kB pathway in macrophages leads to the production of proinflammatory cytokines IL-6 and TNF-alpha. An analysis of monocytes from hospitalized individuals (elderly vs. young) showed higher NF-kB activation but reduced responses to TLR stimulation in elderly populations versus younger controls [81]. Importantly, these studies found that with age, continued stimulation of the NK-kB pathway may lead to immune tolerance and reduced response to subsequent stimuli.…”

Section: Monocyte and Macrophage Traffic To Tissues With Hiv Siv And ...mentioning

confidence: 80%

“…With age, there are increased plasma concentrations of inflammatory mediators (IL-6, IL-10, sICAM-1, sVCAM-1, and MCP-1) that promote monocyte extravasation and subsequent tissue inflammation [79]. Additionally, studies have focused on monocyte and macrophage cytokine dysregulation and NF-kB pathway activation (discussed below) as drivers of inflammation [34,80,81] in the context of HIV and SIV; and HIV, SIV, and aging.…”

Section: Monocyte and Macrophage Traffic To Tissues With Hiv Siv And ...mentioning

confidence: 99%

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Monocytes in HIV and SIV Infection and Aging: Implications for Inflamm-Aging and Accelerated Aging

Wallis

Williams

2022

Viruses

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Before the antiretroviral therapy (ART) era, people living with HIV (PLWH) experienced complications due to AIDS more so than aging. With ART and the extended lifespan of PLWH, HIV comorbidities also include aging—most likely due to accelerated aging—as well as a cardiovascular, neurocognitive disorders, lung and kidney disease, and malignancies. The broad evidence suggests that HIV with ART is associated with accentuated aging, and that the age-related comorbidities occur earlier, due in part to chronic immune activation, co-infections, and possibly the effects of ART alone. Normally the immune system undergoes alterations of lymphocyte and monocyte populations with aging, that include diminished naïve T- and B-lymphocyte numbers, a reliance on memory lymphocytes, and a skewed production of myeloid cells leading to age-related inflammation, termed “inflamm-aging”. Specifically, absolute numbers and relative proportions of monocytes and monocyte subpopulations are skewed with age along with myeloid mitochondrial dysfunction, resulting in increased accumulation of reactive oxygen species (ROS). Additionally, an increase in biomarkers of myeloid activation (IL-6, sCD14, and sCD163) occurs with chronic HIV infection and with age, and may contribute to immunosenescence. Chronic HIV infection accelerates aging; meanwhile, ART treatment may slow age-related acceleration, but is not sufficient to stop aging or age-related comorbidities. Overall, a better understanding of the mechanisms behind accentuated aging with HIV and the effects of myeloid activation and turnover is needed for future therapies.

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“…Minor injuries or traumas are handled in a separate Emergency Room. Other results of the study regarding medication, inflammation and biological aging have been published elsewhere [ 19 , 20 , 21 ]. Reporting of the study follows the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines for cohort studies [ 22 ].…”

Section: Methodsmentioning

confidence: 99%

Risk of Malnutrition upon Admission and after Discharge in Acutely Admitted Older Medical Patients: A Prospective Observational Study

et al. 2021

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There is a lack of knowledge about malnutrition and risk of malnutrition upon admission and after discharge in older medical patients. This study aimed to describe prevalence, risk factors, and screening tools for malnutrition in older medical patients. In a prospective observational study, malnutrition was evaluated in 128 older medical patients (≥65 years) using the Nutritional Risk Screening 2002 (NRS-2002), the Mini Nutritional Assessment-Short Form (MNA-SF) and the Eating Validation Scheme (EVS). The European Society of Clinical Nutrition (ESPEN) diagnostic criteria from 2015 were applied for diagnosis. Agreement between the screening tools was evaluated by kappa statistics. Risk factors for malnutrition included polypharmacy, dysphagia, depression, low functional capacity, eating-related problems and lowered cognitive function. Malnutrition or risk of malnutrition were prevalent at baseline (59–98%) and follow-up (30–88%). The baseline, follow-up and transitional agreements ranged from slight to moderate. NRS-2002 and MNA-SF yielded the highest agreement (kappa: 0.31 (95% Confidence Interval (CI) 0.18–0.44) to 0.57 (95%CI 0.42–0.72)). Prevalence of risk factors ranged from 17–68%. Applying ESPEN 2015 diagnostic criteria, 15% had malnutrition at baseline and 13% at follow-up. In conclusion, malnutrition, risk of malnutrition and risk factors hereof are prevalent in older medical patients. MNA-SF and NRS-2002 showed the highest agreement at baseline, follow-up, and transitionally.

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Alterations of monocyte NF-κB p65/RelA signaling in a cohort of older medical patients, age-matched controls, and healthy young adults

Cited by 23 publications

References 65 publications

Soluble Urokinase Plasminogen Activator Receptor (suPAR) as a Biomarker of Systemic Chronic Inflammation

Soluble Urokinase Plasminogen Activator Receptor (suPAR) as a Biomarker of Systemic Chronic Inflammation

Monocytes in HIV and SIV Infection and Aging: Implications for Inflamm-Aging and Accelerated Aging

Risk of Malnutrition upon Admission and after Discharge in Acutely Admitted Older Medical Patients: A Prospective Observational Study

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