Scientists turned to metabolomics to find cause of biological aging and release index of 25 metabolites that predict healthy and rapid agers
Researchers at the University of Pittsburg Medical Center and the University of Pittsburgh School of Medicine have identified biomarkers in human blood which appear to affect biological aging (aka, senescence). Since biological aging is connected to a person’s overall condition, further research and studies confirming UPMC’s findings will likely lead to a new panel of tests clinical laboratories can run to support physicians’ assessment of their patients’ health.
UPMC’s research “points to pathways and compounds that may underlie biological age, shedding light on why people age differently and suggesting novel targets for interventions that could slow aging and promote health span, the length of time a person is healthy,” according to a UPMC news release.
“We decided to look at metabolites because they’re very dynamic,” Aditi Gurkar, PhD, the study’s senior author, told the Pittsburgh Post-Gazette. Gurkar is Assistant Professor of Medicine, Division of Geriatric Medicine, Aging Institute at the University of Pittsburg. “They can change because of the diet, they can change because of exercise, they can change because of lifestyle changes like smoking,” she added.
The scientists identified 25 metabolites that “showed clear differences” in the metabolomes of both healthy and rapid agers. Based on those findings, the researchers developed the Healthy Aging Metabolic (HAM) Index, a panel of metabolites that predicted healthy agers regardless of gender or race.
“Age is more than just a number,” said Aditi Gurkar, PhD (above), Assistant Professor of Geriatric Medicine at University of Pittsburg School of Medicine and the study’s senior author in a news release. “Imagine two people aged 65: One rides a bike to work and goes skiing on the weekends and the other can’t climb a flight of stairs. They have the same chronological age, but very different biological ages. Why do these two people age differently? This question drives my research.” Gurkar’s research may one day lead to new clinical laboratory tests physicians will order when evaluating their patients’ health. (Photo copyright: University of Pittsburg.)
Clear Differences in Metabolites
According to the National Cancer Institute, a metabolite is a “substance made or used when the body breaks down food, drugs, or chemicals, or its own tissue (for example, fat or muscle tissue). This process, called metabolism, makes energy and the materials needed for growth, reproduction, and maintaining health. It also helps get rid of toxic substances.”
The UPMC researchers used metabolomics—the study of chemical process in the body that involves metabolites, other processes, and biproducts of cell metabolism—to create a “molecular fingerprint” of blood drawn from individuals in two separate study groups.
They included:
People over age 75 able to walk a flight of stairs or walk for 15 minutes without a break, and
People, age 65 to 75, who needed to rest during stair climbing and walk challenges.
The researchers found “clear differences” in the metabolomes of healthy agers as compared to rapid agers, suggesting that “metabolites in the blood could reflect biological age,” according to the UPMC news release.
“Other studies have looked at genetics to measure biological aging, but genes are very static. The genes you’re born with are the genes you die with,” said Gurkar in the news release.
Past studies on aging have explored other markers of biological age such as low grade-inflammation, muscle mass, and physical strength. But those markers fell short in “representing complexity of biological aging,” the UPMC study authors wrote in Aging Cell.
“One potential advantage of metabolomics over other ‘omic’ approaches is that metabolites are the final downstream products, and changes are closely related to the immediate (path) physiologic state of an individual,” they added.
The researchers used an artificial intelligence (AI) model that could identify “potential drivers of biological traits” and found three metabolites “that were most likely to promote healthy aging or drive rapid aging. In future research, they plan to delve into how these metabolites, and the molecular pathways that produce them, contribute to biological aging and explore interventions that could slow this process,” the new release noted.
“While it’s great that we can predict biological aging in older adults, what would be even more exciting is a blood test that, for example, can tell someone who’s 35 that they have a biological age more like a 45-year-old,” Gurkar said. “That person could then think about changing aspects of their lifestyle early—whether that’s improving their sleep, diet or exercise regime—to hopefully reverse their biological age.”
Looking Ahead
The UPMC scientists plan more studies to explore metabolites that promote healthy aging and rapid aging, and interventions to slow disease progression.
It’s possible that the blood-based HAM Index may one day become a diagnostic tool physicians and clinical laboratories use to aid monitoring of chronic diseases. As a commonly ordered blood test, it could help people find out biological age and make necessary lifestyle changes to improve their health and longevity.
With the incidence of chronic disease a major problem in the US and other developed countries, a useful diagnostic and monitoring tool like HAM could become a commonly ordered diagnostic procedure. In turn, that would allow clinical laboratories to track the same patient over many years, with the ability to use multi-year lab test data to flag patients whose biomarkers are changing in the wrong direction—thus enabling physicians to be proactive in treating their patients.
Researchers are discovering it’s possible to determine a person’s age based on the amount of protein in the blood, but the technology isn’t always correct
Mass spectrometry is increasingly finding its way into clinical laboratories and with it—proteomics—the study of proteins in the human body. And like the human genome, scientists are discovering that protein plays an integral part in the aging process.
This is a most interesting research finding. Might medical laboratories someday use proteomic biomarkers to help physicians gauge the aging progression in patients? Might this diagnostic capability give pathologists and laboratory leaders a new product line for direct-to-consumer testing that would be a cash-paying, fast-growing, profitable clinical laboratory testing service? If so, proteomics could be a boon to clinical laboratories worldwide.
When research into genomics was brand-new, virtually no one imagined that someday the direct-to-consumer lab testing model would offer genetic testing to the public and create a huge stream of revenue for clinical laboratories that process genetic tests. Now, research into protein and aging might point to a similar possibility for proteomics.
For example, through proteomics, researchers led by Benoit Lehallier, PhD, Biostatistician, Instructor of Neurology and Neurological Sciences, and senior author Tony Wyss-Coray, PhD, Professor of Neurology and Neurological Sciences and co-director of the Stanford Alzheimer’s Disease Research Center at Stanford University in California, gained an understanding of aging that suggest intriguing possibilities for clinical laboratories.
In their study, published in Nature, titled, “Undulating Changes in Human Plasma Proteome Profiles Across the Lifespan,” the scientists stated that aging doesn’t happen in a consistent process over time, reported Science Alert.
The Stanford researchers also found that they can accurately
determine a person’s age based on the levels of certain proteins in his or her
blood.
Additionally, the study of proteomics may finally explain why blood from young people can have a rejuvenating effect on elderly people’s brains, noted Scientific American.
Each of these findings is important on its own, but taken
together, they may have interesting implications for pathologists who follow
the research. And medical laboratory leaders may find opportunities in mass
spectrometry in the near future, rather than decades from now.
Three Distinct Stages in Aging and Other Findings
The Stanford study found that aging appears to happen at
three distinct points in a person’s life—around the ages 34, 60, and 78—rather
than being a slow, steady process.
The researchers measured and compared levels of nearly 3,000
specific proteins in blood plasma taken from healthy people between the ages of
18 and 95 years. In the published study, the authors wrote, “This new approach
to the study of aging led to the identification of unexpected signatures and
pathways that might offer potential targets for age-related diseases.”
Along with the findings regarding the timeline for aging, the researchers found that about two-thirds of the proteins that change with age differ significantly between men and women. “This supports the idea that men and women age differently and highlights the need to include both sexes in clinical studies for a wide range of diseases,” noted a National Institutes of Health (NIH) report.
“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,” stated Wyss-Coray in the NIH report. “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.”
Tony Wyss-Coray, PhD (above), Professor of Neurology and Neurological Sciences at Stanford University, was senior author of the proteomics study that analyzed blood plasma from 4,263 people between the ages 18-95. “Proteins are the workhorses of the body’s constituent cells, and when their relative levels undergo substantial changes, it means you’ve changed, too,” he said in a Stanford Medicine news article. “Looking at thousands of them in plasma gives you a snapshot of what’s going on throughout the body.” (Photo copyright: Stanford University.)
Differentiating Aging from Disease
Previous research studies also found it is indeed possible
to measure a person’s age from his or her “proteomic signature.”
The researchers published their findings in Aging Cell, a peer-reviewed open-access journal of the Anatomical Society in the UK, titled, “Plasma Proteomic Signature of Age in Healthy Humans.” In it, the authors wrote, “Our results suggest that there are stereotypical biological changes that occur with aging that are reflected by circulating proteins.”
The fact that chronological age can be determined through a
person’s proteomic signature suggests researchers could separate aging from
various diseases. “Older age is the main risk factor for a myriad of chronic
diseases, and it is invariably associated with progressive loss of function in
multiple physiological systems,” wrote the researchers, adding, “A challenge in
the field is the need to differentiate between aging and diseases.”
Can Proteins Cause Aging?
Additionally, the Stanford study found that changes in protein levels might not simply be a characteristic of aging, but may actually cause it, a Stanford Medicine news article notes.
“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,” Wyss-Coray said.
Can Proteins Accurately Predict Age? Not Always
There were, however, some instances where the protein levels inaccurately predicted a person’s age. Some of the samples the Stanford researchers used were from the LonGenity research study conducted by the Albert Einstein College of Medicine, which investigated “why some people enjoy extremely long life spans, with physical health and brain function far better than expected in the 9th and 10th decades of life,” the study’s website notes.
That study included a group of exceptionally long-lived Ashkenazi Jews, who have a “genetic proclivity toward exceptionally good health in what for most of us is advanced old age,” according to the Stanford Medicine news article.
“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,” said Wyss-Coray. So, physical condition is a factor in
proteomics’ ability to accurately prediction age.
Although understanding the connections between protein in
the blood, aging, and disease is in early stages, it is clear additional
research is warranted. Not too long ago the idea of consumers having their DNA
sequenced from a home kit for fun seemed like fantasy.
However, after multiple FDA approvals, and the success of
companies like Ancestry, 23andMe, and the clinical laboratories that serve them,
the possibility that proteomics might go the same route does not seem so
far-fetched.
