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UPMC Researchers Develop Biomarkers That Identify Biological Age While Also Predicting Disease Risk

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.

The researchers published their findings in the journal Aging Cell titled, “A Molecular Index for Biological Age Identified from the Metabolome and Senescence-associated Secretome in Humans.”

“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.

—Donna Marie Pocius

Related Information:

New Study Reveals Molecular Fingerprint of Biological Aging

Blood Test Could Reveal Your Biological Age and Predict Disease Risk

A Molecular Index for Biological Age Identified from the Metabolome and Senescence-associated Secretome in Humans

Family History with Cancer Led Professor into “Healthy Aging” Research

Zombie Cells, Aging and Health

Pitt Researcher Uncovers Cellular Signs of Healthy Aging

True Biological Age is Hidden in Several Newly Identified Blood Markers

The Senescence-associated Secretome as An Indicator of Age and Medical Risk

University of Chicago Study Determines Certain Gut Bacteria Can Help Prevent Food Allergies and Other Gastrointestinal Illnesses

With further research, clinical laboratories may soon be performing macrobiotic testing to measure certain bacterial levels in patients’ gut bacteria

New insights from the University of Chicago (UChicago) into how human microbiota (aka, gut bacteria) play a role in food allergies has the potential to change the way a number of gastrointestinal health conditions are diagnosed and treated. This would give microbiologists and clinical laboratories a greater role in helping physicians diagnose, treat, and monitor patients with these health issues.

Past research has shown that certain gut bacteria can prevent antigens that trigger allergic reactions from entering the bloodstream. For example, Clostridium bacteria in the stomach produce a short-chain fatty acid known as butyrate, a metabolite that promotes the growth of healthy bacteria in the gut. This helps keep the microbiome in balance.

One way butyrate is created in the gut is through the fermentation of fiber. However, a lack of fiber in the diet can deplete the production of butyrate and cause the microbiome to be out of balance. When this happens, a state known as dysbiosis occurs that disrupts the microbiome and can lead to food allergies. 

Without butyrate, the gut lining can become permeable and allow food to leak out of the gastrointestinal tract and into the body’s circulatory system. This reaction can trigger a potentially fatal anaphylactic response in the form of a food allergy. Thus, eating enough fiber is critical to the production of butyrate and to maintaining a balanced microbiome.

But today’s western diet can be dangerously low in soluble fiber. Therefore, the scientists at the University of Chicago have developed “a special type of polymeric molecule to deliver a crucial metabolite produced by these bacteria directly to the gut, where it helps restore the intestinal lining and allows the beneficial bacteria to flourish. … these polymers, called micelles, can be designed to release a payload of butyrate, a molecule that is known to help prevent food allergies, directly in the small and large intestines,” according to a UChicago news release.

This will be of interest to microbiologists, in particular. It’s another example of researchers connecting a specific species of bacteria in the human microbiome to a specific benefit.

The University of Chicago scientists published their findings in the journal Nature Biomedical Engineering titled, “Treatment of Peanut Allergy and Colitis in Mice via the Intestinal Release of Butyrate from Polymeric Micelles.”

Cathryn Nagler, PhD

“It’s very unlikely that butyrate is the only relevant metabolite, but the beauty of this platform is that we can make polymers with other microbial metabolites that could be administered in conjunction with butyrate or other therapies,” said Cathryn Nagler, PhD (above), Bunning Family Professor in the Biological Sciences Division and Pritzker School of Molecular Engineering at UChicago and a senior author of the study. “So, the potential for the polymer platform is pretty much wide open.” As further research validates these findings, clinical labs are likely to be doing microbiomic testing to monitor these therapies. (Photo copyright: University of Chicago.)

Restoring Butyrate in the Gut

One way to treat this anomaly has been through a microbiota transplant—also called a fecal biota transplant—where the administration of a solution of fecal matter is transplanted from a donor into the intestinal tract of the recipient. This transplant alters the recipient’s gut microbial composition to a healthier state, but it has had mixed results. 

So, the UChicago researchers went in another direction (literally). They created an oral solution of butyrate and administered it to mice in the lab. The purpose of the solution was to thwart an allergic reaction when the mice were exposed to peanuts. 

But there was a problem with their oral solution. It was repulsive.

“Butyrate has a very bad smell, like dog poop and rancid butter, and it also tastes bad, so people wouldn’t want to swallow it,” Shijie Cao, PhD, Postdoctoral Scientist at the Pritzker School of Molecular Engineering at UChicago and one of the researchers who worked on the project, told Medical News Today.

The researchers developed a new configuration of polymers that masked the butyrate. They then delivered these polymer micelles directly into the digestive systems of mice that lacked healthy gut bacteria or a proper gut linings.

The treatment restored the microbiome by increasing the production of peptides that obliterate harmful bacteria. This allowed more of the beneficial butyrate-producing bacteria to emerge, which protected the mice from an anaphylactic reaction to peanuts and even reduced the symptom severity in an ulcerative colitis model. 

“We were delighted to see that our drug both replenished the levels of butyrate present in the gut and helped the population of butyrate-producing bacteria to expand,” said Cathryn Nagler, PhD, Bunning Family Professor in the Biological Sciences Division and Pritzker School of Molecular Engineering at the University of Chicago and a senior author of the study, in the press release. “That will likely have implications not only for food allergy and inflammatory bowel disease (IBD), but also for the whole set of non-communicable chronic diseases that have been rising over the last 30 years, in response to lifestyle changes and overuse of antibiotics in our society.”

Future Benefits of UChicago Treatment

According to data from the Asthma and Allergy Foundation of America, about 20 million Americans suffered from food allergies in 2021. This includes approximately 16 million (6.2%) of adults and four million (5.8%) of children. The most common allergens for adults are shellfish, peanuts, and tree nuts, while the most common allergens for children are milk, eggs, and peanuts. 

The best way to prevent an allergic reaction to a trigger food is strict avoidance. But this can be difficult to ensure outside of the home. Therefore, scientists are searching for ways to prevent food allergies from happening in the first place. The micelle technology could be adapted to deliver other metabolites and molecules which may make it a potential platform for treating allergies as well as other inflammatory gastrointestinal diseases

“It’s a very flexible chemistry that allows us to target different parts of the gut,” said Jeffrey Hubbell, PhD, Eugene Bell Professor in Tissue Engineering and Vice Dean and Executive Officer at UChicago’s Pritzker School of Molecular Engineering and one of the project’s principal investigators, in the UChicago news release. “And because we’re delivering a metabolite like butyrate, it’s antigen-agnostic. It’s one agent for many different allergic indications, such as peanut or milk allergies. Once we begin working on clinical trials, that will be a huge benefit.”

Nagler and Hubbell have co-founded a company called ClostraBio to further the development of butyrate micelles into a commercially available treatment for peanut and other food allergies. They hope to begin clinical trials within the next 18 months and expand the technology to other applications as well.  

Further research and clinical trials are needed to prove the validity of using polymer micelles in the treatment of diseases. But it is possible that clinical laboratories will be performing microbiomic testing in the future to help alleviate allergic reactions to food and other substances.

—JP Schlingman

Related Information:

Peanut and Food Allergies May Be Reversed with Compound Produced by Healthy Gut Bacteria

Time Release Polymers Deliver Metabolites to Treat Peanut Allergy and Colitis

Food Allergies: Reversing the Old, Preventing the New with Gut Bacteria

Scientists Reverse Food Allergies by Targeting the Microbiome

Polymers Help Protect Mice from Anaphylactic Reaction to Peanuts, UChicago Research Finds

Treatment of Peanut Allergy and Colitis in Mice via the Intestinal Release of Butyrate from Polymeric Micelles

Expanded Knowledge about Human Metabolome Expected to Fuel Development of New Therapeutic Drugs and Medical Laboratory Tests

Pathologists and clinical laboratory professionals can expect to see new molecular test development as researchers develop new biomarkers in the wake of expanded knowledge of the genome-metabolome-diseasome correlates

One field of science that bears great potential for use in diagnostics and medical laboratory testing involves the human metabolome. Researchers are gaining more understanding of the genetic underpinnings of complex disease and drug response through metabolic pathways.

For example, scientists at the Wellcome Trust Sanger Institute (WTSI) in the United Kingdom have linked 145 genetic regions with more than 400 molecules involved in metabolism in human blood, a story in Genetic Engineering News recently reported. The resulting atlas of associations will enable identification of genes that could be targeted in the development of drugs and clinical laboratory test. (more…)

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