Franck, Maximilien, Tanner, Kamaryn T., Tennyson, Robert L., Daunizeau, Camille, Ferrucci, Luigi, Bandinelli, Stefania, Trumble, Benjamin C., Kaplan, Hillard, Aronoff, Jacob E., Stieglitz, Jonathan, Kraft, Thomas S., Lea, Amanda J., Venkataraman, Vivek, Wallace, Ian J., Lim, Yvonne A.L., Ng, Kee Seong, Sheng Yeong, Joe Poh, Ho, Roger C., Lim, Xinru, Mehrjerd, Ameneh, Charalambous, Eleftheria G., Aiello, Allison E., Pawelec, Graham, Franceschi, Claudio, Hertel, Johannes, Fülöp, Tamàs, Lemoine, Maël, Gurven, Michael and Cohen, Alan A. (2025) Nonuniversality of inflammaging across human populations. Nature aging.

Abstract

Inflammaging, an age-associated increase in chronic inflammation, is considered a hallmark of aging. However, there is no consensus approach to measuring inflammaging based on circulating cytokines. Here we assessed whether an inflammaging axis detected in the Italian InCHIANTI dataset comprising 19 cytokines could be generalized to a different industrialized population (Singapore Longitudinal Aging Study) or to two indigenous, nonindustrialized populations: the Tsimane from the Bolivian Amazon and the Orang Asli from Peninsular Malaysia. We assessed cytokine axis structure similarity and whether the inflammaging axis replicating the InCHIANTI result increased with age or was associated with health outcomes. The Singapore Longitudinal Aging Study was similar to InCHIANTI except for IL-6 and IL-1RA. The Tsimane and Orang Asli showed markedly different axis structures with little to no association with age and no association with age-related diseases. Inflammaging, as measured in this manner in these cohorts, thus appears to be largely a byproduct of industrialized lifestyles, with major variation across environments and populations.