Chronic inflammation explains up to a quarter of aging risk

Low-grade chronic inflammation, sometimes called ‘inflammaging’, has long been considered a central driver of biological aging. But what percentage of the mortality risk associated with accelerated biological aging is actually caused by inflammatory processes? That question has remained unanswered until now. The study analyzed data from 2,532 participants drawn from a nationally representative U.S. cohort, with a mean follow-up of over eighteen years.

The researchers used the DunedinPoAm clock, a measure of biological aging pace derived from DNA methylation patterns. People in the highest quartile of this clock had 2.5 times the mortality risk of those in the lowest quartile. The team then calculated how much of this elevated risk was mediated by inflammatory biomarkers, including CRP, CD4+ T cells, and B cells. That share ranged from 2.3 to 23.5 percent, depending on the method and the specific biomarker examined.

A wide range, a clear signal

That broad margin is telling. It shows that inflammation makes a real contribution to aging-related mortality, but does not tell the whole story. Other mechanisms, such as telomere shortening, mitochondrial dysfunction, or disrupted protein balance, likely play independent roles as well. The researchers also found that people with diabetes are especially vulnerable to the combination of accelerated biological aging and chronic inflammation.

From a longevity perspective, this is significant: reducing inflammation is worthwhile, but will not stop biological aging on its own. The study also suggests that the DunedinPoAm clock performs well across diverse ethnic populations, an improvement over earlier aging clocks validated mainly in homogeneous Western cohorts.

What this means for prevention

Chronic inflammation is partly modifiable through lifestyle: diet, exercise, sleep, and stress management all have documented effects on inflammatory markers. But the study implicitly cautions against overestimation. Targeting inflammation alone addresses only part of the problem. A broader approach targeting multiple aging mechanisms simultaneously is likely to be more effective. These remain findings from an observational study; causal relationships have not been established.

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