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Association of inflammatory mediators with frailty status in older adults: results from a systematic review and meta-analysis

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Abstract

Frailty is a geriatric syndrome defined as a status of extreme vulnerability to stressors, leading to a higher risk of negative health-related outcomes. “Inflammaging”, an age-related state of low-grade chronic inflammation, is characterized by an increased concentration of pro-inflammatory cytokines and acute phase proteins. Inflammaging has been postulated as an underlying mechanism of frailty, and several studies tested the relationship between frailty and concentration of inflammatory mediators. The aim of this systematic review and meta-analysis was to test whether inflammatory mediators are overproduced in frail older adults. Among the 758 articles identified in the literature search, 50 were included in the systematic review, and 39 in the three meta-analyses, i.e., C-reactive protein (CRP), interleukin 6 (IL6), and tumor necrosis factor α. To reduce heterogeneity, meta-analyses were restricted to studies identifying frailty by the Fried et al. [1] [J. Gerontol. A. Biol. Sci. Med. Sci. 56, M146–56] phenotypic criteria. Quantitative analyses measuring the association between frailty and biomarker concentrations showed significant differences when frail subjects were compared to non-frail and pre-frail subjects for CRP and IL6. This work established strong association between inflammatory biomarkers and frailty, confirming the role of age-related chronic inflammation in frailty development.

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Acknowledgments

We want to express our gratitude to Brenner, H. (Division of Clinical Epidemiology and Aging Research, German Cancer Research Center); Collerton, J. (Institute of Ageing and Health and Institute of Cellular Medicine, Newcastle University); Gale, C.R. (HRC Lifecourse Epidemiology Unit, University of Southampton); Sanchís, J. (Department of Cardiology, Hospital Clínico Universitario, University of Valencia); and Wang, X. (Unit of Epidemiology, Fudan University) for sending us their data.

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Funding

This research was funded by Xunta de Galicia [ED431B 2019/02]; Ministerio de Educación, Cultura y Deporte [BEAGAL18/00142 to V.V, PRX19/00353 to B.L.]; and Deputación Provincial de A Coruña [to D.M.-P. and M.S.-F.]. 

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EP, BL, JPT, and JF-T designed the study. DM-P, VV, and MS-F conducted the literature search and screening, data collection, and contacts with authors. SP, SC, and SB carried out the statistical analyses. DM-P, BL, and VV wrote the manuscript draft. All authors reviewed and approved the manuscript draft.

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Correspondence to Blanca Laffon.

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Data for the present meta-analysis were acquired through previously published articles, and the study did not involve participants or patients.

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Marcos-Pérez, D., Sánchez-Flores, M., Proietti, S. et al. Association of inflammatory mediators with frailty status in older adults: results from a systematic review and meta-analysis. GeroScience 42, 1451–1473 (2020). https://doi.org/10.1007/s11357-020-00247-4

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