When it comes to cardiovascular disease, the age of the immune system matters more than chronological age. Today the iAge “inflammatory clock” makes it possible to estimate it. How does it work?

What you will find in this article

• there is a test to estimate immune age: iAge
• the inflammatory score can indicate the immune response and the risk of aging-related diseases
• a study in Bologna identifies supercentenarians with the inflammatory age of a 25-year-old
• the cytokine CXCL9 is a biomarker for cardiovascular disease

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Immune age

How much are we at risk of chronic diseases? More than chronological age, what matters is the age of the immune system. A research group from Stanford University and the Buck Institute for Research on Aging has developed a tool to estimate our immune age, an “inflammatory clock”, which is based on a series of parameters of the inflammation linked to aging. Obtained thanks to an algorithm of artificial intelligence, the new clock is called iAge and was presented in a paper published in Nature Aging.

Studying the immune system

The researchers studied the blood tests of about 1,000 volunteers of various ages, including many older adults, taking part in the Immunome. The analyses, carried out in 2010, assessed the levels of certain cytokinesCytokines are small proteins produced by the immune system, which bind to specific receptors present on the cell membrane and communicate to the cell a specific set of instructions such as, for example, the stimulus to grow, or to differentiate or even the order to die. They are produced by different types of cells and, once released in the body, induce specific reactions in adjacent cells (paracrine effect), in others far away (endocrine effect) or in those that have created them (autocrine effect)., that is, molecules produced when there is inflammation (the same ones also generated in excess in patients with severe COVID-19). The parameters also included the concentration of various types of immune cells and the overall activity of thousands of genes within these cells.

The aim was to quantify inflammation, an inflammation that is not good which tends to increase over time and is not necessarily aligned with chronological age. The authors then compared the blood values collected years earlier with certain health parameters and the presence of diseases, and examined the impact of inflammation on mortality, validating the results against data from other samples under study. They also included data from an ongoing study in Bologna, which includes a group of exceptionally long-lived people.

Some studies on the oldest old confirm that chronological age and immune age do not always correspond

The inflammatory clock

The data were then combined and processed using an artificial intelligence (AI). AI made it possible to create the “inflammatory clock”, which suggests theimmune age. In the architecture of the inflammatory clock, the levels of 50 cytokines are decisive; their values, processed by the algorithm, returned the inflammatory score associated both with the immune response and with the person’s risk of developing numerous aging-related diseases.

The model works: blood tests on the oldest old in Bologna showed that their inflammatory age was on average 40 years lower, and one supercentenarian had an inflammatory age of 25.

The authors found that among the substances central to estimating the age of the immune system is a protein, the cytokine CXCL9, which attracts immune cells to the site of an infection and which shows a sharp increase after age 60.

Watch out for the heart and more

This cytokine, produced not only by the immune system but also by the endothelial cells lining the inner walls of blood vessels, plays a role in various cardiovascular diseases.

A further analysis of a subsample of almost 100 participants showed that high concentrations of the cytokine CXCL9 and of the other inflammatory molecules are linked to a higher risk of certain diseases. In particular, there is increased arterial stiffness, which in turn is associated with a higher risk of heart attack, stroke and kidney failure, and a thickening of the left ventricular wall.

Studies in animal models have also reported that lowering CXCL9 levels could also restore proper functioning of endothelial cells, which would become younger again.

The cytokine CXCL9 seems to be a biomarker for the risk of cardiovascular disease: the higher its concentration, the greater the risk

The research is still in its early stages, but it opens a path to better understanding why some people develop chronic diseases more easily than others. The goal is to be able to assess individual risk and recognize in advance any conditions or disorders that may worsen over time, in order to treat them early.