Abstract
Chronic low-grade inflammation has long been considered an important part of the aging process (“inflamm-aging”). However, measurement of this process is highly variable across studies, often relying on a single marker such as C-reactive protein or interleukin-6, despite evidence for greater complexity. Several studies have now tackled multivariate approaches to integrating the signals of multiple inflammation-related cytokines in order to measure the process of inflamm-aging. On the surface, the results appear discordant, even when using the same data set. Here we review and compare these studies. We show that apparent discrepancies can easily be explained by minor methodological differences across studies. There is a single, coherent interpretation of inflamm-aging as a simultaneous up-regulation of both pro- and anti-inflammatory cytokines. This interpretation is robustly detectable with different methods and data sets. Single markers do not provide a reliable signal, but small numbers of markers can be easily integrated to provide a much more reliable metric. We recommend a minimum of 3–4 markers, including one of the soluble TNF receptors, IL-6, and some choice within TNF-α, IL-1RA, IL-18, and CRP. More broadly, these findings confirm the need for multivariate and complex systems approaches to understand underlying physiological processes.