STANFORD, Calif. — An “aging clock” that can predict a person’s likelihood of death and disease may be sitting in the human immune system. Researchers at Stanford Medicine say the natural timing device diagnoses life-threatening illnesses years before symptoms develop.
It’s even more accurate than the number of candles on your birthday cake and can predict levels of frailty in old age seven years before it happens. The artificial intelligence tool identifies at-risk individuals early, when drugs and lifestyle changes are more likely to work. It’s based on blood-borne proteins that drive chronic inflammation.
“Every year, the calendar tells us we’re a year older,” explains senior author Professor David Furman from The Buck Institute for Research on Aging in a university release. “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.”
The phenomenon is due to differing rates at which people’s immune systems decline. They become less effective as we grow older, leading to systemic inflammation. This process also fuels organ damage and life-threatening conditions, including cardiovascular disease, cancer, and dementia.
iAge more accurate than the naked eye?
Now, study authors say they’ve come up with a metric that measures the process for the first time. It’s built on the idea that levels of specific immune cells and proteins fluctuate throughout life — which the team call a person’s “iAge.”
Prof. Furman says the clock opens the door to curing illnesses or staving them off. The team analyzed blood samples from 1,001 individuals between eight to 96 years-old as part of a project called “1,000 Immunomes.”
Those with an older iAge showed patterns of systemic inflammation sooner. They were also prone to multiple long-term health problems including lowered immunity, cardiovascular disease, and frailty. The strongest predictors were a set of around 50 proteins called cytokines.
These findings enabled the AI computer brain to generate a single figure inflammatory score. It tracked a person’s immunological response and the likelihood of incurring any of a variety of age-related diseases.
When the researchers assessed the fitness of about 30 seniors seven years later, iAge proved superior to chronological age. They measured the participants’ speed at getting up from a chair, walking to a fixed distance, and their ability to live independently.
Dr. Furman and colleagues also obtained blood samples from 29 exceptionally long-lived people in Italy. They had iAges averaging 40 years less than their calendar age. One, a 105-year-old man, had an inflammatory age of 25.
One protein is key to the body’s deterioration
Researchers confirmed their results through data from the Framingham Study. It has tracked the health of people from one Massachusetts town since 1948. The comparisons found a significant link between levels of cytokines and mortality rates from all diseases. One protein in particular, CXCL9, contributed more than any other clock component to the iAge score.
That cytokine is secreted by certain immune cells to attract others to the site of an infection. It soars after people reach age 60 and has a strong connection to hardening of the arteries, heart attacks, and strokes.
The chemical is also found in endothelial cells that line the walls of blood vessels. Old age correlated with a significant increase in CXCL9, diminishing the ability to form micro-vascular networks that dilate and contract.
In lab experiments on human cells and tissue from mice, reducing these levels restored youthful endothelial cell function. This suggests CXCL9 directly contributes to dysfunction and inhibiting it combats cardiovascular disease.
“Our inflammatory aging clock’s ability to detect subclinical accelerated cardiovascular aging hints at its potential clinical impact,” Furman says. “All disorders are treated best when they’re treated early.”
“Standard immune metrics which can be used to identify individuals most at risk for developing single or even multiple chronic diseases of aging have been sorely lacking,” the researcher adds in a media release.
“Bringing biology to our completely unbiased approach allowed us to identify a number of metrics, including a small immune protein which is involved in age-related systemic chronic inflammation and cardiac aging. We now have means of detecting dysfunction and a pathway to intervention before full-blown pathology occurs.”
Finding aging hallmarks to prevent disease
When it comes to health and longevity, the age of a person’s immune system trumps the chronological information from a driver’s license.
“On average, centenarians have an immune age that is 40 years younger than what is considered ‘normal’ and we have one outlier, a super-healthy 105 year-old man (who lives in Italy) who has the immune system of a 25 year old,” Prof. Furman continues.
The study author adds iAge can help track someone’s risk of developing multiple chronic diseases by assessing the cumulative physiological damage to their immune system.
“Using iAge it’s possible to predict seven years in advance who is going to become frail,” Furman says. “That leaves us lots of room for interventions.”
In 2013, a group of researchers studying aging identified nine “hallmarks” of the aging process. Age-related immune system dysfunction was not part of the mix.
“It’s becoming clear that we have to pay more attention to the immune system with age, given that almost every age-related malady has inflammation as part of its etiology,” Furman concludes.
“If you’re chronically inflamed, you will have genomic instability as well as mitochondrial dysfunction and issues with protein stability. Systemic chronic inflammation triggers telomere attrition, as well as epigenetic alterations. It’s clear that all of these nine hallmarks are, by and large, triggered by having systemic chronic inflammation in your body. I think of inflammation as the 10th hallmark.”
The findings appear in the journal Nature Aging.
SWNS writer Mark Waghorn contributed to this report.