Why ageing differs: Inflammation may be more lifestyle than biology

For years, scientists have believed that inflammation inevitably increases with age, quietly fuelling diseases like heart disease, dementia and diabetes. But a new study of Indigenous populations challenges that idea and could reshape how we think about ageing itself.

For decades, scientists have identified chronic low-level inflammation – called “inflammaging” – as one of the primary drivers of age-related diseases. Think of it as your body’s immune system stuck in overdrive – constantly fighting battles that don’t exist, gradually wearing down organs and systems.

But inflammaging might not be a universal feature of ageing after all. Instead, it could be a byproduct of how we live in modern society.

The research, published in Nature Aging, compared patterns of inflammation in four very different communities around the world. Two groups were from modern, industrialised societies – older adults living in Italy and Singapore.

The other two were Indigenous communities who live more traditional lifestyles: the Tsimane people of the Bolivian Amazon and the Orang Asli in the forests of Malaysia.

The researchers analysed blood samples from more than 2,800 people, looking at a wide range of inflammatory molecules, known as cytokines. Their goal was to find out whether a pattern seen in earlier studies – where certain signs of inflammation rise with age and are linked to disease – also appears in other parts of the world. 

The answer, it turns out, is both yes and no.

Among the Italian and Singaporean participants, the researchers found a fairly consistent inflammaging pattern. As people aged, levels of inflammatory markers in the blood, such as C-reactive protein and tumour necrosis factor, rose together. Higher levels were linked to a greater risk of chronic diseases including kidney disease and heart disease.

But in the Tsimane and Orang Asli populations, the inflammaging pattern was absent. The same inflammatory molecules did not rise consistently with age, and they were not strongly linked to age-related diseases. 

In fact, among the Tsimane, who face high rates of infections from parasites and other pathogens, inflammation levels were often elevated. Yet this did not lead to the same rates of chronic diseases that are common in industrialised nations.

Despite high inflammatory markers, the Tsimane experience very low rates of conditions such as heart disease, diabetes and dementia.  Inflammaging may not be universal

These results raise important questions. One possibility is that inflammaging, at least as measured through these blood signals, is not a universal biological feature of ageing. Instead, it may arise in societies marked by high-calorie diets, low physical activity and reduced exposure to infections.

In other words, chronic inflammation linked to ageing and disease might not simply result from an inevitable biological process, but rather from a mismatch between our ancient physiology and the modern environment.

The study suggests that in communities with more traditional lifestyles – where people are more active, eat differently and are exposed to more infections – the immune system may work in a different way. In these groups, higher levels of inflammation might be a normal, healthy response to their environment, rather than a sign that the body is breaking down with age.

Another possibility is that inflammaging may still occur in all humans, but it might appear in different ways that are not captured by measuring inflammatory molecules in the blood. It could be happening at a cellular or tissue level, where it remains invisible to the blood tests used in this research. 

  Why this matters

If these findings are confirmed, they could have significant consequences.

First, they challenge how we diagnose and treat chronic inflammation in ageing. Biomarkers used to define inflammaging in European or Asian populations might not apply in other settings, or even among all groups within industrialised nations.

Second, they suggest that lifestyle interventions aimed at lowering chronic inflammation, such as exercise, changes in diet, or drugs targeting specific inflammatory molecules, might have different effects in different populations. What works for people living in cities might be unnecessary, or even ineffective, in those living traditional lifestyles.

Finally, this research serves as an important reminder that much of our knowledge about human health and ageing comes from studies conducted in wealthy, industrialised nations. Findings from these groups cannot automatically be assumed to apply worldwide. 

The researchers are clear: this study is just the beginning. They urge scientists to dig deeper, using new tools that can detect inflammation not just in the blood, but within tissues and cells where the real story of ageing may be unfolding. Just as important, they call for more inclusive research that spans the full range of human experience, not just the wealthy, urbanised corners of the world.

At the very least, this study offers an important lesson. What we thought was a universal truth about the biology of ageing might instead be a local story, shaped by our environment, lifestyle and the way we live.