Immune SystemImmune System “Clock” Successfully Predicts Illness and Mortality

Immune System “Clock” Successfully Predicts Illness and Mortality

Scientists at Stanford University’s School of Medicine and the Buck Institute for Research of Aging have successfully built what they are calling an immune system “clock.” This new piece of technology could accurately predict the strength of your immune system, how soon you’ll become frail or whether you have an underlying condition that may lead to complications later in life.

Along with the creation of their predictive clock, published in the peer-reviewed journal Nature Aging, the scientists also discovered that a bloodborne substance may accelerate cardiovascular aging.

“Every year, the calendar tells us we’re a year older,” said David Furman, Ph.D., the study’s senior author. “But not 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.”

Furman and his colleagues say that this unpredictability in health is primarily caused by the different rates at which our immune systems begin to decline. Our immune systems are a specific set of cells that are specially designed to fight infections or other injuries caused by pathogens. When these cells detect an infection, they respond quickly with what is known as acute inflammation. This “good inflammation,” as it is often called, will generally last for a few days, and will subside shortly after.

There is another type of inflammation, however, a “bad inflammation”, that occurs in everyone. As we age, this “bad inflammation” begins to spread throughout the body. This chronic inflammation is the cause of a slew of medical problems such as cancer, heart attacks, strokes, neurodegeneration, and autoimmunity.

Furman and his colleagues wanted to see if they could use this “bad inflammation” to try and see if there was an accurate way to predict these problems and find ways to stop them.

What is an Immune System “Clock”?

What is an Immune System “Clock”?

The group of scientists used blood samples from 1,001 healthy individuals between the ages of 8-96 from 2009 to 2016. The goal was to examine the levels of immune-signaling proteins called cytokines, as well as the overall activity of thousands of different genes in various cells. These levels were analyzed using artificial intelligence to form their immune system “clock.”

The team found that there were a set of 50 cytokines that were the strongest predictors of inflammatory age. Using these, they were able to create an algorithm that generated a “score” that was able to accurately predict a person’s immune response and risk of age-related diseases.

With their immune system “clock” in hand, the team then examined participants of a similar study who were over the age of 65. They measured the participants’ speed at standing from a seated position, walking a specific distance, mental questionnaires, and their overall ability to live independently. What they found was that the score given by the immune system “clock” was “far more accurate than biological age in predicting fragility seven years later.”

To further assess the validity of the immune system “clock”, the team examined data from a study conducted in Bologna, Italy on 29 “exceptionally long-lived individuals”. They used their immune system “clock” to give scores to the older group, and compared them with those of 18 50-79-year-olds. The older group from Italy had an inflammatory age, given by the “clock”, that averaged nearly 40 years less than their biological calendar age. One 105-year-old man had an inflammatory age of 25, according to Furman.

The team also examined data from the Framingham Study, an ongoing study that has been tracking the health of thousands of individuals since 1948. Using their “clock”, the team was able to accurately assess the mortality in the study’s participants. What they found was that high levels of activity in cytokine-producing genes were “significantly correlated with all-cause mortality among Framingham Study participants.” This means that not only can the team’s immune system “clock” predict future health risks, but also an individual’s overall risk of early death.

Along with their “clock,” the group also found that a bloodborne substance, known as CXCL9, contributed more to a person’s inflammatory age score. CXCL9 is a cytokine that is secreted by immune cells to alert the immune system of infection. The group found that levels of CXCL9 begin to rise significantly once a person reaches the age of 60.

Using a group of nearly 100 participants aged 25-90, all of which were chosen for their “remarkable health”, the scientist began to look for signs of cardiovascular disease or deterioration. What they found was that in participants with higher levels of CXCL9, there was a heightened risk for strokes, heart attacks, and kidney failure.

“Our inflammatory aging clock’s ability to detect subclinical accelerated cardiovascular aging hints at its potential clinical impact,”

While more research is needed on the use of this new inflammatory immune system “clock,” Ferman and his team are hopeful that their discovery can be used to help screen for age-related health conditions.

“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.”

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