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Clinical Laboratories and Pathology Groups

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Clinical Laboratories and Pathology Groups

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Proteomics May Hold Key to Understanding Aging’s Role in Chronic Diseases and Be Useful as a Clinical Laboratory Test for Age-related Diseases

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.”

Toshiko Tanaka, PhD, Research Associate with the Longitudinal Study Section, Translational Gerontology Branch, National Institute of Aging (NIG), National Institute of Health (NIH), Baltimore, led a study into proteomics which concluded that more than 200 proteins are associated with age.

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.

—Dava Stewart

Related Information:

Our Bodies Age in Three Distinct Shifts, According to More than 4,000 Blood Tests

Fountain of Youth? Young Blood Infusions ‘Rejuvenate’ Old Mice

Undulating Changes in Human Plasma Proteome Profiles Across the Lifespan

Blood Protein Signatures Change Across Lifespan

Plasma Proteomic Signature of Age in Healthy Humans

Stanford Scientists Reliably Predict People’s Age by Measuring Proteins in Blood

Advancements That Could Bring Proteomics and Mass Spectrometry to Clinical Laboratories

Might Proteomics Challenge the Cult of DNA-centricity? Some Clinical Laboratory Diagnostic Developers See Opportunity in Protein-Centered Diagnostics

More Clinical Laboratories and Genetic Testing Companies Are Sharing Gene Sequencing Data That Involve Variations

The National Institute of Health’s ClinVar public database of genetic variation is demonstrating good accuracy, and a handful of clinical labs are learning to share and review this relatively small genetic database

In the analysis of genomic variants, data sharing is proving to be an important tool for researchers, scientists, pathologists, and clinical laboratory scientists.

Accessible databases like ClinVar, which was launched by the National Institute of Health (NIH) in 2013, have emerged to aggregate genetic sequencing with acceptable results. ClinVar exists to meet the needs of the medical genetics community. It collaborates with organizations to make pertinent genetic information available.

ClinVar is an archive of compiled data relating to genotype and phenotype variations among humans. Through this database, individuals can present and peruse submissions regarding variants found in patient samples.

ClinVar is averaging about 6,000 submissions per month by both commercial laboratory companies and reference labs. Major contributors to the database include: (more…)

NIH Funds Nine Anti-Microbial Resistance Diagnostic Projects to Deal with ‘Super Bugs’ and Give Clinical Laboratories New Diagnostic Tools to Improve Patient Care

Lab-on-a-chip technology could reduce the time needed to identify infection-causing bacteria and for physicians to prescribe correct antibiotics 

Pathology groups and medical laboratories may see their role in the patient-care process grow if researchers succeed in developing culture-independent diagnostic tools that quickly identify bacterial infections as well as pinpoint the antibiotics needed to treat them.

In the battle against antibiotic-resistant infections (AKA “super bugs”) the National Institutes of Health (NIH) is funding nine research projects aimed at thwarting the growing problem of life-threatening infections that no longer are controlled or killed by today’s arsenal of drugs.

Common Practices in Hospitals Leading to Super Bugs

Currently, when infections are suspected in hospitals or other settings where illness can quickly spread, samples are sent to a central medical laboratory where it may take up to three days to determine what germ is causing the infection. Because of that delay, physicians often prescribe broad-spectrum antibiotics based on a patient’s symptoms rather than lab test results, a practice that can lead to the growth of antibiotic-resistant microbes. (more…)

Researchers at Columbia University Report How Exome Sequencing Helped Diagnose Patients with Unknown Disorders

More precise diagnoses will encourage pathologists and clinical laboratory professionals to consider using exome sequencing for clinical diagnostic purposes

Having sequenced the exomes of 150 patients to diagnose unknown disorders over the past year, physicians at Columbia University (CU) used that information to make decisive diagnoses in one-third of the cases. It is evidence from one of the nation’s pioneering gene-sequencing programs that such data can improve how physicians identify disease.

Findings from Exome Sequencing Program Noteworthy for Pathologists

Pathologists will find it noteworthy that some of the patients in the exome-sequencing program had been tracked for years at CU without a definitive diagnosis. This is why clinicians at the academic center in New York City see value in exome sequencing for selected patients.

For more than a year, doctors at Columbia University have tested the exome’s capability to provide a correct diagnosis for patients with suspected genetic disorders of unknown origins. The primary goal of the program is to prove that sequencing the exomes of these patients is both clinically useful and cost effective in guiding physicians to a correct diagnosis. (more…)

Why Smartphones May Be the Best Business Opportunity in Healthcare

Pathologists take note: 80% of physicians will be using mobile technology by 2012

Meet “mHealth!” That’s the new term to describe how mobile devices are used in the delivery of healthcare to patients. Many clinical laboratories and pathology groups already have laboratory informatics solutions that support how their client physicians use mHealth solutions in patient care.

Experts predict that Smartphones will dominate mobile healthcare (mHealth) in just a few short years. The enabling tools will be mobile applications (apps) that monitor such conditions as diabetes, hypertension, coronary heart disease and asthma. Smart phones will also be used to order medical laboratory tests and access clinical laboratory test data.
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