A new kind of age “clock” can assess chronic inflammation and predict whether someone is at risk of developing age-related disorders such as cardiovascular or neurodegenerative diseases.
This takes into account the state of health, and he may be older or younger than the chronological age of the person.
The Inflammatory Aging Clock is one of the first tools of its kind to measure health through inflammation.
Other age watches use epigenetic markers – a group of chemicals that mark a person’s DNA according to age and are passed on as cells divide.
The researchers who developed iAge hope the tool will help doctors determine who will benefit from the intervention, as inflammation is treatable.
This study is important not only for predicting unhealthy aging but also as a mechanism for promoting it.Vishwa Deep Dixit – Immunobiologist at Yale Medical School in New Haven, Connecticut
iAge is based on the idea that as we age, the body experiences chronic systemic inflammation due to damaged cells and the release of inflammatory molecules, which ultimately leads to tissue wear and tear.
It can neutralize this inflammation to some extent, but others accelerate aging.
To develop iAge, a team of systems biologist David Furman and vascular specialist Nazish Sayed of Stanford University in California was part of the 1000 Immunomes project to investigate 8-8 chronic systemic features.
They tested blood samples from 1001 children, 96 years of age.
As the person got older, the researchers used information about the age and health of the participants, combined with machine learning algorithms, to identify the protein markers in the blood that most clearly indicate inflammation.
In particular, they identified the immune signalling protein or cytokine CXCL9 as one of the key components; It occurs mainly in the lining of blood vessels and is associated with the development of heart disease.
Syed says that CXCL9, a key component of iAge, gives new meaning to the dictum “You are as old as an artery.”
After its development, researchers tested the iAge by taking blood from 19 people who lived to be 99 years old and using tools to calculate their biological ages.
On average, people over 100 years of age with iAge are 40 years younger than they are.
According to the press release, this is in line with the idea that people with healthier immune systems tend to live longer.
Scientists have long been looking for the idea of an aging clock to predict how healthy a person is today.
While epigenetics-based research in this area offers some promise, Maria Mitterbrunn, a molecular biologist at the Autonomous University of Madrid, discovered human biology by measuring epigenetic changes in DNA.
He argues that estimating age can be very difficult. It has become easier to measure inflammation with blood tests, making instruments like the iAge more practical in a clinical setting.
Farman hopes that the inflammation-based iAge and other age meters will also make personalized treatment possible.
After studying CXCL9 as a biomarker of systemic inflammation, Ferman and colleagues artificially aged the human endothelial cells that make up the walls of blood vessels by growing them in plates and dividing them several times. Researchers have found that high protein levels cause cells to become dysfunctional.
When detected early, “inflammation is one of the best treatments for it,” says Mittelbrunn.
“We have developed a great anti-inflammatory agent, so I think this is a biological process that we are well aware of and that is easy to target.”
For example, researchers talk about salicylic acid. I have known for a long time (starting material for aspirin production) and recently developed a JAK / STAT inhibitor for inflammatory conditions such as rheumatoid arthritis.
Syed envisions a future in which everyone can regularly obtain profiles of inflammatory biomarkers to track the risk of developing age-related diseases.
“If we could control aging in a more influential way, I think we would have a more graceful aging process,” he said.
What Biomarkers Predict the Inflammatory Clock of Aging (iAge)?
Using a non-linear comparison, iAge scores correlate with a variety of inflammatory markers as measured by levels of existing immune system molecules and associated pathways.
Multiple diseases are the accumulation of many chronic inflammatory diseases.
Multiple diseases and mean age show a strong correlation.
For subjects over 60 years of age, an increase in iAge was associated with an increase in morbidity.
The researchers also found that the total number of T cells and B cells, leukocytes that play a role in the immune response, showed a similar correlation.
For a group of participants aged 100 and over, scientists compared their average age with their actual age.
Of the 19 participants, 68 showed relatively low iAge scores, while only 31% were in the high range group. A control group of older adults found that only 23% of subjects had low iAge scores.
Participants aged 100 and over showed significantly lower iAge scores at lower levels, suggesting that “iAge is associated with exceptional longevity.”
Immunology Trusted Source describes the decline and dysfunction of the immune system with age.
The immunogenetic-related protein CXCL9 made the largest contribution to the iAge sample.CXCL9 is a small protein that regulates inflammatory and immune responses.
In the early period, this protein is positively correlated with age, and its level increases significantly by the age of 60. The main mechanism of immunogenicity of
CXCL9 may be through altered function. The correct function of the endothelial cells that are present in the lining.
Blood vessels and their normal function are to regulate blood flow; however, damaged endothelial cells can contribute to inflammation.
Investigation of the role of this protein in mice showed that endothelial cells with a large amount of CXCL9 were damaged in aged mice.
These damaged cells lead to atherosclerosis.
Other studies have also shown that these damaged endothelial cells lead to thickening of the heart muscle; Such conditions are precursors of cardiovascular disease.
Scientists hypothesize that as CXCL9 production increases with age, endothelial cells are damaged, amplifying the inflammatory signals that cause cardiovascular disease.
However, when the researchers inhibited CXCL9 in mice, they partially restored correct endothelial cell function. This enhances the potential of a therapy targeting CXCL9 as a preventative measure to slow cell aging and disease.