Stanford University Researchers Develop New Blood-Based Diagnostics That Can Indicate Your True Biological Age And Overall Health Status
A team of Stanford University School of Medicine scientists have developed a new blood diagnostic platform that functions as a kind of physiological clock: monitoring the levels of 373 proteins circulating in one’s blood. If the protein levels are out of the recommended levels, it can indicate critical issues about a person’s health and stage of biological aging.
Dr Tony Wyss-Coray, PhD, professor of neurology and neurological sciences, the D. H. Chen Professor II and co-director of the Stanford Alzheimer’s Disease Research Center told Thailand Medical
News, “We’ve known for a long time that measuring certain proteins in the blood can give you information about a person’s health status, lipoproteins for cardiovascular health, for example. But it hasn’t been appreciated that so many different proteins’ levels, roughly a third of all the ones we looked at change markedly with advancing age.”
Dr Wyss-Coray added that changes in the levels of numerous proteins that migrate from the body’s tissues into circulating blood not only characterize, but quite possibly cause, the phenomenon of aging
A study paper describing the research was published in Nature Medicine. Dr Wyss-Coray is the senior author. The lead author is neurology instructor Benoit Lehallier, PhD.
The medical researchers analyzed plasma,the cell-free, fluid fraction of blood from 4,263 people ages 18-95.
Dr Wyss-Coray commented, “Proteins are the workhorses of the body’s constituent cells, and when their relative levels undergo substantial changes, it means you’ve changed, too. Looking at thousands of them in plasma gives you a snapshot of what’s going on throughout the body.”
The research results suggest that physiological aging does not simply proceed at a perfectly even pace, but rather seems to chart a more herky-jerky trajectory, with three distinct inflection points in the human life cycle. Those three points, occurring on average at ages 34, 60 and 78, stand out as distinct times when the number of different blood-borne proteins that are exhibiting noticeable changes in abundance rises to a crest. This happens because instead of simply increasing or decreasing steadily or staying the same throughout life, the levels of many proteins remain constant for a while and then at one point or another undergo sudden upward or downward shifts. These shifts tend to bunch up at three separate points in a person’s life: young adulthood, late middle age and old age.
The researchers built their clock by looking at composite levels of proteins within groups of people rather than in individuals. But the resulting formula proved able to predict individuals’ ages within a range of three years most of the time. And when it didn’t, there was an interesting upshot: People whose predicted age was substantially lower than their actual one turned out to be remarkably healthy for their age.
The scientists obtained their samples from two large studies. One of them, known as the LonGenity study, has assembled a registry of exceptionally long-lived Ashkenazi Jews. It was able to provide many blood samples from people as old as 95.
Upon measuring the levels of roughly 3,000 proteins in each individual&
amp;rsquo;s plasma, Wyss-Coray’s team identified 1,379 proteins whose levels varied significantly with participants’ age. A reduced set of 373 of those proteins was sufficient for predicting participants’ ages with great accuracy, the study said. But there were cases of substantial divergence between participants’ chronological and physiological age for example, among the subjects in the LonGenity study, with their genetic proclivity toward exceptionally good health in what for most of us is advanced old age.
Dr Wyss-Coray added, “We had data on hand-grip strength and cognitive function for that group of people. Those with stronger hand grips and better measured cognition were estimated by our plasma-protein clock to be younger than they actually were.”
The research also strengthened the case that men and women, who were about equally represented in the study, age differently. Of the proteins the analysis found to change with age, 895 or nearly two-thirds were significantly more predictive for one sex than for the other.
Dr Wyss-Coray said that the differences were striking. He added that this finding strongly supports the rationale for the National Institutes of Health’s policy, instituted in 2016, promoting increased inclusion of women in clinical trials and the demarcating of sex as a biological variable.
He indicated that any clinical applications of the technique are a good five to 10 years off. With further validation, though, it could be used not only to identify individuals who appear to be aging rapidly and, therefore, at risk of age-linked conditions such as Alzheimer’s disease or cardiovascular disease but also to find drugs or other therapeutic interventions, like leafy green vegetables, that slow the aging process, or conversely to flash an early warning of a drug’s unanticipated tendency to accelerate aging.
Dr Wyss-Coray further added,“Ideally, you’d want to know how virtually anything you took or did affects your physiological age.”
Although the words “373 proteins” may conjure up the image of a transfusion-sized blood extraction, a drop is all it takes for a 373-protein readout.
In reality, a mere nine proteins were enough to do a passable job, Wyss-Coray said. “After nine or 10 proteins, adding more proteins to the clock improves its prediction accuracy only a bit more,” he said. “With machine learning, you could potentially make a test with good accuracy based on just those nine proteins.”
Reference: Undulating changes in human plasma proteome profiles across the lifespan. Benoit Lehallier et al. Nature Medicine, VOL 25 December 2019 1843–1850, https://doi.org/10.1038/s41591-019-0673-2.