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.