A new form of age “clock” can evaluate chronic inflammation and forecast if someone is in danger of age-related diseases including cardiovascular and neurological disease. The clock gauges a person’s biological age, which takes into account their health and might be greater or lower than their chronological age.
The inflammatory aging clock (iAge), published in Nature Aging on July 12th, is one of the first instruments of its type to measure health using inflammation. Other age clocks have relied on epigenetic markers, which are chemical groups that tag a person’s DNA as they age and are handed down during cell division.
Because inflammation is curable, the researchers behind iAge believe that the tool will aid doctors in determining who might benefit from intervention, perhaps increasing the number of years a person lives in good health.
According to Vishwa Deep Dixit, an immunobiologist at Yale School of Medicine in New Haven, Connecticut, who was not involved in the study, it “further reinforces the idea that the immune system is essential, not just for forecasting unhealthy aging, but also as a mechanism driving it.”
The concept behind iAge is that when a person ages, their body endures chronic, systemic inflammation as a result of damaged cells emitting inflammation-causing chemicals. This eventually causes damage to their tissues and organs.
People with a strong immune system will be able to reduce inflammation to some level, while others will age more quickly.
To create iAge, a team at Stanford University in California, led by systems biologist David Furman and vascular specialist Nazish Sayed, analyzed blood samples from 1,001 people aged 8 to 96 who are part of the 1000 Immunomes Project, which aims to learn how chronic, systemic inflammation signatures change as people age.
The researchers utilized a machine-learning algorithm to determine the protein markers in the blood that most clearly signify systemic inflammation, based on the individuals’ chronological ages and health information.
They identified CXCL9, an immune-signaling protein or cytokine that is mostly generated by the inner lining of blood vessels and has been linked to the development of heart disease, as a major contributor.
CXCL9’s role in iAge, according to Sayed, lends additional validity to the cliché that “you’re only as old as your arteries.”
The researchers put iAge to the test by taking blood samples from 19 people who had lived to be at least 99 years old and using the technology to determine their biological age.
According to a press release, the centenarians had an iAge 40 years lower than their actual age, which aligns with the concept that persons with stronger immune systems live longer.
Scientists have long investigated the use of age clocks as a predictor of a person’s present health.
Although epigenetics-based research has shown promise in this field, Mara Mittelbrunn, a molecular biologist at the Autonomous University of Madrid, believes that determining a person’s biological age by detecting epigenetic alterations in their DNA can be difficult.
It would be easy to measure inflammation using a blood test, making technology like iAge more useful in a clinical context.
Furman believes that iAge and other inflammation-based aging clocks will also enable tailored therapies.
Furman and his colleagues produced human endothelial cells, which make up the walls of blood arteries, in a dish and artificially aged them by letting them divide repeatedly to look for CXCL9 as a biomarker of systemic inflammation.
The scientists discovered that excessive amounts of protein caused the cells to become dysfunctional. The cells restored some function after the researchers suppressed the gene that produces CXCL9, suggesting that the protein’s detrimental effects may be reversible.
“Inflammation is one of the best things we can cure if identified early,” adds Mittelbrunn. “We’ve created some incredible anti-inflammatory technologies, so I believe it’s a biological process about which we know a lot and can easily target.”
For example, scientists have long known about salicylic acid (a component of aspirin) and have recently discovered JAK/STAT inhibitors to treat inflammatory diseases like rheumatoid arthritis.
Sayed sees a future in which anybody may get frequent inflammatory-biomarker profiling to monitor their risk of developing the age-related illness. “I believe we can have a more elegant aging process if we can manage aging in a more significant way,” he adds.