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

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.

Keywords: C-reactive protein; Frailty; Inflammaging; Interleukin 6; Older adults; Tumor necrosis factor alpha.

Fig. 1

Flow chart: selection of the literature

Fig. 2

Forest plots of CRP concentration (sensitivity analyses excluding Hwang et al. [38] and Marcos-Pérez et al. [51]): a frailty vs. non-frailty groups; b pre-frailty vs. non-frailty groups; c frailty vs. pre-frailty groups. In order to respect original data provided by Walston et al. (2002), two populations from this study were included in these meta-analyses, which differ in the inclusion (a) or exclusion (b) of participants with cardiovascular diseases history and diabetes

Fig. 3

Forest plots of IL6 concentration (sensitivity analyses excluding Marcos-Pérez et al. [51]): a frailty vs. non-frailty groups; b pre-frailty vs. non-frailty groups; c frailty vs. pre-frailty groups

Fig. 4

Forest plots of TNFα concentration (sensitivity analyses excluding Marcos-Pérez et al. [51]): a frailty vs. non-frailty groups; b pre-frailty vs. non-frailty groups; c frailty vs. pre-frailty groups