Inflammaging

Published in : Nature Aging, Maximilian Franck et al, Nonuniversality of Inflammaging across Human Populations, June  2025

Context

Inflammaging—the chronic, low-grade inflammation that rises with age—is widely considered a hallmark of aging and a key driver of chronic age-related diseases such as cardiovascular disease, diabetes, and neurodegeneration. Most of this evidence, however, comes from industrialized societies.

This new study asks a critical question: Is inflammaging a truly universal feature of human aging, or is it specific to certain environments?

The Study

Researchers compared inflammatory cytokine patterns in four diverse populations:

Two from industrialized settings

·        Italy’s InCHIANTI cohort

·        Singapore Longitudinal Aging Study

Two from nonindustrialized, high-infection environments:

·        Tsimane of the Bolivian Amazon

·        Indigenous Orang Asli of Peninsular Malaysia

In the industrialized cohorts, inflammaging scores—derived from a panel of 19 cytokines—increased clearly with age and were strongly associated with chronic diseases, especially chronic kidney disease.

In contrast, among the Tsimane and the Orang Asli, the cytokine patterns differed markedly. Despite high baseline inflammation due to infections, these populations showed no consistent inflammaging axis, no association with age, and no link between inflammatory markers and chronic disease outcomes.

This suggests that elevated inflammation in these Indigenous groups is driven by their infectious environments rather than by aging per se—and that this inflammation does not result in the chronic diseases typically seen in industrialized societies.

Why Do We Care?

This study directly challenges the assumption that inflammaging is a universal biological process. Instead, it supports the idea that inflammaging, as we currently define and measure it, may be largely a consequence of industrialized lifestyles: poor diet, low physical activity, chronic stress, and environmental exposures.

Importantly, it also opens the door to a more nuanced view of inflammation. In some environments, chronic immune activation may be adaptive—or at least not harmful. The same levels of cytokines that predict disease in one population may be benign or even protective in another.

Key points

Inflammaging is not inevitable. It depends on context: how and where we live is important. Lifestyle, environment, and systemic exposures can modify the extent of inflammaging.