How much are we at risk of chronic diseases? Our immune system age is more important than our chronological age. A research team from Stanford University and the Buck Institute for Research on Aging have developed a tool to estimate our immune age, an ‘inflammatory clock’, leveraging on a number of age-related inflammation parameters. Based on an artificial intelligence algorithm, 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 1000 volunteers of various age-groups, including many elderly people, participating in the Immunome project. 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)., aka molecules produced by an inflammation status (the same molecules are also excessively generated in patients with severe Covid-19). Among the studied parameters, The concentration of different types of immune cells and their genetic activity have been included.
The inflammatory clock is based on several parameters of age-related inflammation
The main goal was on quantifying inflammation, not the good one, that tends to increase over time and is not necessarily aligned with age. Next, the authors compared blood values collected years earlier with certain parameters of health status, the presence of disease, and on mortality. They cross-validated the results with data from other clinical studies’ blood samples. Among them, the ones owned by an ongoing study in Bologna (Italy) on centenarians.
Alcuni studi sui grandi anziani confermano che non sempre l’età anagrafica e quella immunitaria corrispondono
The inflammatory clock
All data have been then combined and reprocessed by using an artificial intelligence (AI) algorithm. The AI was able to create the ‘inflammatory clock’, which suggests immune age. The architecture core of the inflammatory clock is based upon the levels of 50 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).; the algorithm was able to process their specific values and provide the inflammatory score associated with the immune response capability and the individual risk of developing several age-related diseases.
Artificial intelligence quantifies ‘bad’ inflammation and returns an Immune-Age score
The model works: in Bologna, the centenarians’ blood tests showed that their average Immune-Age was 40 years younger than regular folks, and the ultra-centenarians (beyond 110 y.o.) had an Immune-age of a 25 years person.
The authors discovered that the cytokine CXCL9 level is the leading factor across all the immune-system parameters, this protein is strongly linked to infections and dramatically increases after the age of 60.
Immune age is not always aligned with a person’s age
Beware of the heart and beyond
This specific cytokine, produced not only by the immune system but also by the blood vessels’ endothelial cells, plays a role in various cardiovascular diseases.
Further analysis of a subsample of almost 100 participants showed that high concentrations of the cytokine CXCL9 and other inflammatory molecules exposed to an increased risk of certain diseases. In particular, it has been discovered that it increases arterial stiffness, associated with an increased risk of heart attack, stroke and kidney failure, and an enlarged left ventricular wall.
Studies in animal models have also shown that lowering CXCL9 levels could also restore proper functioning of endothelial cells, which would become younger again.
La citochina CXCL9 sembra essere un biomarcatore per il rischio di patologie cardiovascolari: più è alta la sua concentrazione, maggiore è il rischio
The research is still at the starting blocks, but it opens to a better way of understanding why some people develop chronic diseases more easily than others. The aim is to be able to assess individual risk and recognise in advance any conditions or disorders that may worsen over time, in order to treat them early.