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      Frailty in Older Adults Is Associated With Plasma Concentrations of Inflammatory Mediators but Not With Lymphocyte Subpopulations

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          Abstract

          Frailty denotes a multidimensional syndrome that gives rise to vulnerability to stressors and leads to an increase of the age-related decline of different physiological systems and cognitive abilities. Aging-related alterations of the immune system may compromise its competence culminating in a chronic low-grade inflammation state. Thus, it has been proposed that frailty is associated with alterations in the concentration of pro-inflammatory molecules and in different lymphocyte subpopulations. To provide further support to the validity of that hypothesis, we conducted a cross-sectional study in a population of Spanish older adults ( N = 259, aged 65 and over) classified according to their frailty status. Biomarkers analyzed included percentages of several lymphocyte subsets and several inflammation mediators, namely concentrations of interleukin 6 (IL6), C-reactive protein (CRP), tumor necrosis factor α (TNFα), and 75 kDa soluble TNFα receptor II (sTNF-RII). Reference ranges for the inflammation mediators were established for the first time in robust older adults. A significant increase in the CD4 +/CD8 + ratio and a significant decrease in the % CD19 + cells were observed in the frail group. Progressive increases with frailty severity were obtained in all inflammatory mediator concentrations, especially notable for IL6 and sTNF-RII. Area under the receiver-operating characteristic curve obtained for sTNF-RII (0.90, 95% CI 0.85–0.94, P < 0.001) indicates a high accuracy in the predictive value of this biomarker for frailty. Although results from the current study revealed limited strength associations between frailty and the lymphocyte subsets assessed, data obtained for the inflammatory mediators provide further support to involvement of inflammaging in frailty status in older adults.

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          Inflammatory markers in population studies of aging.

          To review findings from major epidemiologic studies regarding risk factors for and consequences of elevated markers of inflammation in older adults. Most large, current epidemiologic studies of older adults have measured serum interleukin-6 (IL-6), C-reactive protein (CRP) and tumor necrosis factor alpha (TNF-alpha) and some studies also include more extensive batteries of measures including soluble receptors. There are few defined risk factors for the modest elevations in inflammatory markers seen with aging. These include visceral adiposity, lower sex steroid hormones, smoking, depression and periodontal disease. Of the markers assessed, IL-6 is most robustly associated with incident disease, disability and mortality. Though correlated with age, the etiology of elevated inflammatory markers remains incompletely defined. Inflammation, especially IL-6 may be a common cause of multiple age-related diseases or a final common pathway by which disease leads to disability and adverse outcomes in older adults. Future research targeting inflammation should examine these pathways. Copyright © 2011. Published by Elsevier B.V.
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            Frailty: An Emerging Public Health Priority.

            The absolute and relative increases in the number of older persons are evident worldwide, from the most developed countries to the lowest-income regions. Multimorbidity and need for social support increase with age. Age-related conditions and, in particular, disabilities are a significant burden for the person, his or her family, and public health care systems. To guarantee the sustainability of public health systems and improve the quality of care provided, it is becoming urgent to act to prevent and delay the disabling cascade. Current evidence shows that too large a proportion of community-dwelling older people present risk factors for major health-related events and unmet clinical needs. In this scenario, the "frailty syndrome" is a condition of special interest. Frailty is a status of extreme vulnerability to endogenous and exogenous stressors exposing the individual to a higher risk of negative health-related outcomes. Frailty may represent a transition phase between successful aging and disability, and a condition to target for restoring robustness in the individual at risk. Given its syndromic nature, targeting frailty requires a comprehensive approach. The identification of frailty as a target for implementing preventive interventions against age-related conditions is pivotal. Every effort should be made by health care authorities to maximize efforts in this field, balancing priorities, needs, and resources. Raising awareness about frailty and age-related conditions in the population is important for effective prevention, and should lead to the promotion of lifelong healthy behaviors and lifestyle.
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              Aging, frailty and age-related diseases.

              The concept of frailty as a medically distinct syndrome has evolved based on the clinical experience of geriatricians and is clinically well recognizable. Frailty is a nonspecific state of vulnerability, which reflects multisystem physiological change. These changes underlying frailty do not always achieve disease status, so some people, usually very elderly, are frail without a specific life threatening illness. Current thinking is that not only physical but also psychological, cognitive and social factors contribute to this syndrome and need to be taken into account in its definition and treatment. Together, these signs and symptoms seem to reflect a reduced functional reserve and consequent decrease in adaptation (resilience) to any sort of stressor and perhaps even in the absence of extrinsic stressors. The overall consequence is that frail elderly are at higher risk for accelerated physical and cognitive decline, disability and death. All these characteristics associated with frailty can easily be applied to the definition and characterization of the aging process per se and there is little consensus in the literature concerning the physiological/biological pathways associated with or determining frailty. It is probably true to say that a consensus view would implicate heightened chronic systemic inflammation as a major contributor to frailty. This review will focus on the relationship between aging, frailty and age-related diseases, and will highlight possible interventions to reduce the occurrence and effects of frailty in elderly people.
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                Author and article information

                Contributors
                URI : https://frontiersin.org/people/u/558487
                URI : https://frontiersin.org/people/u/558510
                URI : https://frontiersin.org/people/u/277746
                URI : https://frontiersin.org/people/u/264081
                URI : https://frontiersin.org/people/u/305520
                URI : https://frontiersin.org/people/u/192762
                URI : https://frontiersin.org/people/u/4654
                URI : https://frontiersin.org/people/u/390473
                URI : https://frontiersin.org/people/u/92594
                URI : https://frontiersin.org/people/u/91027
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                16 May 2018
                2018
                : 9
                : 1056
                Affiliations
                [1] 1Universidade da Coruña, DICOMOSA Group, Department of Psychology, Area of Psychobiology, Faculty of Education Sciences , A Coruña, Spain
                [2] 2Department of Cell and Molecular Biology, Faculty of Sciences, Universidade da Coruña , A Coruña, Spain
                [3] 3Gerontology Research Group, Instituto de Investigación Biomédica de A Coruña (INIBIC), Universidade da Coruña , A Coruña, Spain
                [4] 4Division of Biological Chemistry, Biocenter, Innsbruck Medical University , Innsbruck, Austria
                [5] 5ISPUP-EPIUnit, Universidade do Porto , Porto, Portugal
                Author notes

                Edited by: Diana Boraschi, Istituto di biochimica delle proteine (IBP), Italy

                Reviewed by: Gunnar Lachmann, Charité Universitätsmedizin Berlin, Germany; Paola Bossù, Fondazione Santa Lucia (IRCCS), Italy

                *Correspondence: Blanca Laffon, blaffon@ 123456udc.es

                These authors have contributed equally to this work.

                These authors have contributed equally to the senior authorship of this manuscript.

                Specialty section: This article was submitted to Cytokines and Soluble Mediators in Immunity, a section of the journal Frontiers in Immunology

                Article
                10.3389/fimmu.2018.01056
                5964167
                29868017
                8e848687-6191-4608-95de-516ad6bf183c
                Copyright © 2018 Marcos-Pérez, Sánchez-Flores, Maseda, Lorenzo-López, Millán-Calenti, Gostner, Fuchs, Pásaro, Laffon and Valdiglesias.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 28 March 2018
                : 27 April 2018
                Page count
                Figures: 2, Tables: 3, Equations: 0, References: 51, Pages: 9, Words: 6697
                Categories
                Immunology
                Original Research

                Immunology
                c-reactive protein,interleukin 6,frailty,inflammaging,lymphocyte subpopulations,tumor necrosis factor α,soluble tnfα receptor ii

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