Inflammaging could be exclusive to industrialized societies.

Aging is associated with increased chronic inflammation, a phenomenon known as inflammaging, which is linked to various diseases and was previously thought to be universal. Now, an international team has analyzed data on 19 inflammation-associated proteins in four different populations: two industrialized (from Italy and Singapore) and two non-industrialized (the Tsimane population of the Bolivian Amazon and the Orang Asli population of Malaysia). The results show that inflammation, long considered a hallmark of aging, may not be a universal human experience, according to this study by a team from the Mailman School of Public Health at Columbia University (USA). The research suggests that “aging inflammation”—a chronic, low-grade inflammation associated with aging—appears to be a byproduct of industrialized lifestyles and varies significantly among global populations. The results have been published in ' Nature Aging '.

The researchers analyzed data from four populations: two industrialized groups, the Italian InCHIANTI study and the Singapore Longitudinal Study on Ageing (SLAS), and two non-industrialized Indigenous populations, the Tsimane of the Bolivian Amazon and the Orang Asli of the Malaysian Peninsula. While the inflammaging signature was similar between the two industrialized populations, it did not hold true in the Indigenous groups , where inflammation levels were largely determined by infections rather than age.

"In industrialized settings, we see a clear relationship between inflammation and diseases like chronic kidney disease," says lead author Alan Cohen. "But in populations with high infection rates, inflammation appears to reflect the burden of infectious disease more than aging itself."

Interestingly, although Indigenous populations, particularly the Tsimane, had high constitutive levels of inflammation, these did not increase with age and, more importantly, did not lead to the chronic diseases that plague industrialized societies. Indeed, most chronic diseases—diabetes, heart disease, Alzheimer's, etc.— are rare or virtually nonexistent in Indigenous populations , meaning that even when Indigenous youth have profiles that at first glance appear similar to those of older industrialized adults, these profiles do not lead to pathological consequences.

"These findings really challenge the idea that inflammation is bad in and of itself," Cohen says. "Rather, it appears that inflammation—and perhaps other aging mechanisms as well—may be highly context-dependent. On the one hand, that's challenging, because there won't be one-size-fits-all answers to scientific questions . On the other hand, it's promising, because it means we can intervene and change things."

The study used a panel of 19 cytokines, small immune signaling proteins, to assess patterns of inflammation. While these markers aligned with aging in the Italian and Singaporean datasets, they were not replicated among the Tsimane and Orang Asli, whose immune systems were shaped by persistent infections and distinct environmental exposures.

Among the main conclusions, the study showed that inflammatory markers were strongly related to chronic diseases in industrialized populations, but not in indigenous groups.

The study challenges the hypothesis of universal biomarkers of aging and suggests, instead, that immunological aging processes are population-specific and strongly influenced by the exposome—the totality of environmental, lifestyle, and infectious exposures.

"These results point to an evolutionary mismatch between our immune systems and the environments we currently live in," Cohen explains. "It's possible that inflammatory aging isn't a direct product of aging, but rather a response to industrialized conditions."

The findings highlight the importance of considering cultural, environmental, and lifestyle factors when investigating aging processes, and challenge existing paradigms surrounding inflammatory aging.

The authors call for a re-evaluation of how aging and inflammation are measured in populations and emphasize the need for standardized, context-sensitive tools. “Factors such as the environment, lifestyle—for example, intense physical activity or a very low-fat diet—and infections can all influence the aging of the immune system,” Cohen adds. “Understanding how these elements interact could help develop more effective global health strategies.”