Chronic Inflammation is Important in the Progression of Aging

A biological mechanism might be important in aging if it is comparatively easy to produce good correlations between measures of the progression of that mechanism and mortality rates. The effects of minor contributions to aging can be swamped when looking at human data, since you can't carefully construct your study populations and follow them for their entire lives - it is hard to pick out small effects using statistical analysis of general study data. But if every study group consistently shows strong associations for the measure at hand, then that is a sign that there is something worth looking into there.

It is well known that chronic inflammation is a bad sign when it comes to long-term health. On the one hand higher levels of constant inflammation are produced by conditions that are harmful in and of themselves, such as the functional decline of the immune system and an excess of visceral fat tissue and the lifestyle choices needed to produce it, and so on. On the other hand chronic inflammation is also harmful in and of itself, a dysfunction in the normal operation of metabolism and destructive to tissues, a process that contributes to the progression of numerous age-related conditions.

Here is an example that demonstrates how straightforward it is now to find good correlations between measure of inflammation and human mortality, and that these correlations are very consistent across study populations:

Simple Biologically Informed Inflammatory Index of Two Serum Cytokines Predicts 10 Year All-Cause Mortality in Older Adults

In total, 15 nuclear factor-kappa B-mediated pathway markers of inflammation were first measured in baseline serum samples of 1,155 older participants in the InCHIANTI population. Of these, C-reactive protein, interleukin-1-receptor antagonist, interleukin-6, interleukin-18, and soluble tumor necrosis factor-α receptor-1 were independent predictors of 5-year mortality. These five inflammatory markers were measured in baseline serum samples of 5,600 Cardiovascular Health Study participants. A weighted summary score, the first principal component summary score, and an inflammation index score were developed from these five log-transformed inflammatory markers, and their prediction of 10-year all-cause mortality was evaluated in Cardiovascular Health Study and then validated in InCHIANTI.

The inflammation index score that included interleukin-6 and soluble tumor necrosis factor-α receptor-1 was the best predictor of 10-year all-cause mortality in Cardiovascular Health Study, after adjusting for age, sex, education, race, smoking, and body mass index compared with all other single and combined measures. The inflammation index score was also the best predictor of mortality in the InCHIANTI validation study. Stratification by sex and [cardiovascular disease] status further strengthened the association of inflammation index score with mortality.

[Thus] a simple additive index of serum interleukin-6 and soluble tumor necrosis factor-α receptor-1 best captures the effect of chronic inflammation on mortality in older adults among the 15 biomarkers measured.

A great deal of chronic inflammation is self-inflicted in this age of low-cost and widely available calories. Eat to excess and become fat, and you pile an additional burden on yourself that will wear you down into age-related disease far earlier than your peers, all other things being equal. Even small amounts of excess visceral fat tissue held for years have a large impact on health in later life. Calorie restriction and regular exercise seem to be the optimal way to go when it comes to making the most of an imperfect biology.

As to the rest of it, the chronic inflammation that you cannot avoid because it stems from low-level biological damage to your immune system and tissues that happens to everyone, no matter how good your health, the best you can do today is to support the research that will lead to rejuvenation treatments tomorrow. Reverse the damage, restore the immune system, and that will remove the causes of chronic inflammation. That can't be done today, but it will be possible in the near future. Just how near depends on fundraising and advocacy here and now: new medicine doesn't just emerge from nothing.


Since low cost self-test kits are available for HbA1C and cholesterol blood levels, I hope that pharmaceutical companies will also provide low cost kits to test these two cytokines. It would provide quick feedback that would allow us to optimize dietary/exercise/life-style regimens.

Posted by: Lou Pagnucco at February 5th, 2014 1:55 PM

Thank you very much for this article. Just so you know, I went on a cruise a few years ago and got alarmed because I saw fat people, and I saw old people, but I saw NO FAT OLD PEOPLE. I kept looking for days on a ship with about 2000 people, but couldn't find one! Time to go back on that severe CRdiet (i.e. 1200 calories per day). It is an inefficient way to lose weight, but when I was on it all my good health indicators skyrocketed (I suffered a setback when I lost both parents, but it has been a year now, so...).

Posted by: Brad Arnold at February 18th, 2014 2:24 PM

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