Stanford Researchers Create AI-Powered Immune System 'Clock' That Predicts How Well You'll Age

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by Tyler Durden
Wednesday, Jul 14, 2021 - 10:50 PM

Researchers at the Stanford University School of Medicine and the Buck Institute for Research have developed a method for predicting how strong your immune system is, how soon you'll become frail, and whether a person has undiscovered cardiovascular problems that could lead to serious illness down the road.

"[N]ot all humans age biologically at the same rate. You see this in the clinic — some older people are extremely disease-prone, while others are the picture of health," said senior author David Furman, PhD, who runs Stanford's 1000 Immunomes Project.

Published July 12 in Nature Aging, the 26-author collaboration found that bloodbourne inflammation markers hold the key to how one will age.

This divergence, Furman said, traces in large part to differing rates at which people’s immune systems decline. The immune system — a carefully coordinated collection of cells, substances and strategies with which evolution has equipped us to deal with threats such as injuries or invasions by microbial pathogens — excels at mounting a quick, intense, localized, short-term, resist-and-repair response called acute inflammation. This “good inflammation” typically does its job, then wanes within days. (An example is that red, swollen finger you see when you have a splinter, and the rapid healing that follows.)

As we grow older, a low-grade, constant, bodywide “bad inflammation” begins to kick in. This systemic and chronic inflammation causes organ damage and promotes vulnerability to a who’s who of diseases spanning virtually every organ system in the body and including cancer, heart attacks, strokes, neurodegeneration and autoimmunity.

To date, there have been no metrics for accurately assessing individuals’ inflammatory status in a way that could predict these clinical problems and point to ways of addressing them or staving them off, Furman said. But now, he said, the study has produced a single-number quantitative measure that appears to do just that. -Stanford Medicine

For the study, blood samples were taken from 1,001 healthy people ranging in age from 8-96, between 2009 and 2016. The samples were "subjected to a barrage of analytical procedures determining levels of immune-signaling proteins called cytokines, the activation status of numerous immune-cell types in responses to various stimuli, and the overall activity levels of thousands of genes in each of those cells," according to the report.

Using artificial intelligence, the data was fed into a composite analysis referred to by researchers as an 'inflammatory clock,' which finds that the strongest predictors of inflammatory age are contained within 50 immune-signaling proteins called cytokines. When run through the 'complex algorithm,' the markers were sufficient to generate a single-number inflammatory score that reflects a person's immunological response - including the likelihood of suffering from a variety of aging-related diseases.

In particular, researchers tracked 30 participants in Furman's 1000 Immunomes Project participants aged 65 or older whose blood was drawn in 2010. They measured how quickly participants were able to get up from a chair and walk a fixed distance, as well as their ability to live independently via questionnaire ("Can you walk by yourself? Do you need help getting dressed?"). In doing so, they found that 'inflammatory age' was a better predictor than chronological age at predicting frailty seven years later.

Furman also studied an exceptionally long-lived population in Bologna, Italy - comparing the inflammatory ages of 28 centenarians and one sub-centenarian to 18 subjects with ages ranging between 50-79 years, and found that the aged Italians had inflammatory ages averaging 40 years less than their calendar age. One 105-year-old participant had an inflammatory age of just 25, according to Furman.

To further assess inflammatory age’s effect on mortality, Furman’s team turned to the Framingham Study, which has been tracking health outcomes in thousands of individuals since 1948. The Framingham study lacked sufficient data on bloodborne-protein levels, but the genes whose activity levels largely dictate the production of the inflammatory clock’s cytokines are well known. The researchers measured those cytokine-encoding genes’ activity levels in Framingham subjects’ cells. This proxy for cytokine levels significantly correlated with all-cause mortality among the Framingham participants. -Stanford Medicine

Keep in mind, many scientists believe COVID-19 should be treated as an acute inflammatory disease, in which critical patients often experience a 'cytokine storm.'

More via Stanford Medicine:

A Key Substance:

The scientists observed that blood levels of one substance, CXCL9, contributed more powerfully than any other clock component to the inflammatory-age score. They found that levels of CXCL9, a cytokine secreted by certain immune cells to attract other immune cells to a site of an infection, begin to rise precipitously after age 60, on average.

Among a new cohort of 97 25- to 90-year-old individuals selected from the 1000 Immunomes Project for their apparently excellent health, with no signs of any disease, the investigators looked for subtle signs of cardiovascular deterioration. Using a sensitive test of arterial stiffness, which conveys heightened risk for strokes, heart attacks and kidney failure, they tied high inflammatory-age scores — and high CXCL9 levels — to unexpected arterial stiffness and another portent of untoward cardiac consequences: excessive thickness of the wall of the heart’s main pumping station, the left ventricle.

CXCL9 has been implicated in cardiovascular disease. A series of experiments in laboratory dishware showed that CXCL9 is secreted not only by immune cells but by endothelial cells — the main components of blood-vessel walls. The researchers showed that advanced age both correlates with a significant increase in endothelial cells’ CXCL9 levels and diminishes endothelial cells’ ability to form microvascular networks, to dilate and to contract.

But in laboratory experiments conducted on tissue from mice and on human cells, reducing CXCL9 levels restored youthful endothelial-cell function, suggesting that CXCL9 directly contributes to those cells’ dysfunction and that inhibiting it could prove effective in reducing susceptible individuals’ risk of cardiovascular disease.

Our inflammatory aging clock’s ability to detect subclinical accelerated cardiovascular aging hints at its potential clinical impact,” Furman said. “All disorders are treated best when they’re treated early.”