Summary: A global study challenges the long-held view that chronic inflammation is a universal marker of human aging. By comparing industrialized populations with Indigenous groups, researchers found that what is often called “inflammaging” is strongly influenced by lifestyle, environment, and infectious exposures rather than being an inevitable, biology-wide feature of aging.
In industrialized settings, low-grade chronic inflammation tends to rise with age and is linked to age-related diseases. In contrast, among non-industrialized Indigenous populations inflammation levels are stable across the lifespan, driven primarily by infection, and do not translate into the same chronic disease burden. These results suggest that inflammation and other biomarkers of aging may be context-dependent and shaped by the exposome—our cumulative environmental, lifestyle, and infectious experiences.
Key facts
- Context-dependent inflammaging: Markers of chronic inflammation increased with age in two industrialized cohorts but not in two Indigenous cohorts.
- Infection versus degenerative aging: Elevated inflammation among Indigenous participants reflected infection burden rather than age-related immune decline.
- Implications for biomarkers: The findings challenge the use of universal aging biomarkers and call for context-aware tools that account for population-specific exposures.
Source: Columbia University
New evidence from Columbia University Mailman School of Public Health suggests inflammaging may not be a universal human phenomenon. The study argues that chronic, low-grade inflammation commonly associated with aging in industrialized nations appears to be a byproduct of modern environmental and lifestyle factors, and varies substantially across global populations.
Published in Nature Aging, the research analyzed immune marker data from four distinct populations: two industrialized cohorts (the Italian InCHIANTI study and the Singapore Longitudinal Aging Study) and two Indigenous, non-industrialized groups (the Tsimane of the Bolivian Amazon and the Orang Asli of Peninsular Malaysia).
Researchers measured a panel of 19 cytokines—small proteins that mediate immune communication—to identify an “inflammaging” axis previously observed in the InCHIANTI dataset. The signature that aligned with aging in the Italian and Singaporean cohorts did not replicate among the Tsimane and Orang Asli. In these Indigenous populations, immune profiles reflected persistent infectious exposures and environmental differences rather than an age-driven increase in chronic inflammation.
Lead author Alan Cohen, PhD, associate professor of Environmental Health Sciences at Columbia Mailman School and faculty with the Butler Columbia Aging Center, emphasized the contrast: “In industrialized populations we see clear links between inflammaging and diseases such as chronic kidney disease. In high-infection populations, inflammation more closely tracks infectious burden than aging itself.”
Key study observations include:
- High prevalence of infection among Indigenous participants: roughly two-thirds of Tsimane had intestinal parasites and more than 70 percent of Orang Asli showed prevalent infections.
- Inflammaging markers correlated with chronic disease outcomes in industrialized cohorts but showed little or no association with age-related diseases in Indigenous groups.
- Overall cytokine axis structures differed markedly across populations, indicating immune-aging processes are shaped by environment and exposure history.
Notably, although some Indigenous participants had relatively high baseline inflammation, those levels did not increase with age nor did they predict the chronic illnesses common in industrialized societies, such as diabetes, cardiovascular disease, or Alzheimer’s disease. This decoupling suggests that inflammation alone is not inherently pathological; its consequences depend on ecological and lifestyle context.
“These results point to an evolutionary mismatch between ancestral immune programming and modern industrial environments,” Cohen explained. “Inflammaging, as we measured it here, may largely reflect industrialized conditions rather than a universal biological aging process.”
The authors recommend rethinking how we measure aging and immune decline globally, advocating for standardized but context-aware biomarkers that incorporate environmental, lifestyle, and infectious factors. Understanding how physical activity, diet, pathogen exposure, and other elements of the exposome interact with immune aging could inform more effective, population-tailored public health strategies.
Co-authors are listed in the manuscript. Funding for the study was provided by the Impetus program, the French National Research Agency (ANR) under Investments for the Future, the Deutsche Forschungsgemeinschaft (DFG), and the Intramural Research Program of the U.S. National Institute on Aging.
About this aging and inflammation research news
Author: Stephanie Berger
Source: Columbia University
Contact: Stephanie Berger – Columbia University
Image: Image credit: Neuroscience News
Original research: Nonuniversality of inflammaging across human populations, by Alan Cohen et al., published in Nature Aging. The research evaluated cytokine-based inflammaging axes across diverse cohorts and concluded that immune-aging patterns differ substantially by population and exposure history.
Abstract
Nonuniversality of inflammaging across human populations
Inflammaging, defined as an age-associated increase in chronic inflammation, is widely considered a hallmark of aging. However, circulating cytokine profiles used to measure inflammaging vary, and no consensus biomarker set exists. This study tested whether an inflammaging axis based on 19 cytokines identified in the Italian InCHIANTI cohort generalizes to a different industrialized population (the Singapore Longitudinal Aging Study) and to two Indigenous, nonindustrialized populations (the Tsimane and the Orang Asli).
The Singapore cohort largely mirrored InCHIANTI results except for a few markers, while the Tsimane and Orang Asli exhibited different cytokine axis structures with little to no association with age and no link to age-related diseases. These results indicate that inflammaging, as measured here, is largely a product of industrialized lifestyles and varies substantially across environments and populations.