A new type of age clock can assess chronic inflammation to predict whether someone is at risk for developing age-related diseases such as cardiovascular and neurodegenerative diseases. The clock measures “biological age”, which takes health into account and can be higher or lower than a person’s chronological age.
The Inflammatory Aging Clock (iAge) reported on July 12 in Aging in nature, is one of the first tools of its kind to use inflammation to assess health. Other age clocks have used epigenetic markers, chemical groups that mark a person’s DNA as they age and are passed on as cells divide. The researchers who developed iAge hope the tool could help doctors determine who would benefit from an intervention since inflammation is treatable – and potentially extend the number of years a person lives in good health.
The study “is further confirmation that the immune system is critical, not just in predicting unhealthy aging, but also as a driving mechanism,” says Vishwa Deep Dixit, an immunobiologist at the Yale School of Medicine in New Haven, Connecticut was not involved in the work.
iAge is based on the idea that a person’s body experiences chronic, systemic inflammation as they age because their cells are damaged and release molecules that trigger inflammation. This ultimately leads to wear and tear on their tissues and organs. People with healthy immune systems can neutralize this inflammation to some extent, while others age faster.
To develop iAge, a team led by systems biologist David Furman and vascular specialist Nazish Sayed from Stanford University in California analyzed blood samples from 1,001 people aged 8 to 96, who are part of the 1000 Immunomes Project, which aims to examine how signatures are chronic, systemic inflammation changes with age. The researchers used the participants’ chronological age and health information combined with a machine learning algorithm to identify the protein markers in the blood that most clearly signal systemic inflammation. In particular, they identified the immune signaling protein or cytokine CXCL9 as a major contributor; it is mainly produced by the inner lining of the blood vessels and has been linked to the development of heart disease.
Sayed says that as a key component of iAge, CXCL9 adds credibility to the saying “You’re Only As Old As Your Arteries”.
Once developed, the researchers tested iAge by collecting the blood of 19 people who were at least 99 years old and using the tool to calculate their biological ages. On average, centenarians had an iAge 40 years below their real age, according to a press release – which is consistent with the notion that people with healthier immune systems tend to live longer.
Scientists have explored the idea of age clocks as a predictor of how healthy a person is currently. Epigenetic research in this area has shown promise, but María Mittelbrunn, molecular biologist at the Autonomous University of Madrid, says assessing a person’s biological age by measuring epigenetic changes in their DNA can be complicated. Measuring inflammation with a blood test would be easier, which would make an instrument like iAge more practical for a clinical setting.
Furman hopes iAge and other inflammation-based age watches could also enable personalized treatments.
In studying CXCL9 as a biomarker of systemic inflammation, Furman and colleagues cultured human endothelial cells, which make up the walls of blood vessels, in a shell and artificially aged them by repeatedly dividing them. The researchers found that high levels of the protein drove the cells into a dysfunctional state. When the team silenced expression of the gene encoding CXCL9, the cells regained some function, suggesting that the protein’s harmful effects may be reversible.
Recognized early on, “inflammation is one of the best things we can treat,” says Mittelbrunn. “We have developed amazing anti-inflammatory agents, so I think it’s a biological process that we have a lot of knowledge about and that we can easily address.” For example, researchers have long known about salicylic acid (a starting material for making Aspirin) and more recently have developed JAK / STAT inhibitors for inflammatory diseases such as rheumatoid arthritis.
Sayed envisions a future where anyone can regularly undergo inflammatory biomarker profiling to keep track of their risk of developing an age-related disease. “If we can control aging more effectively,” he says, “I believe we can have a more graceful aging process.”
This article is reproduced with permission and was first published on July 13, 2021.