More research into accelerated aging may lead to new clinical laboratory and anatomic pathology testing biomarkers for early-onset cancer
Could accelerated aging be contributing to the rise in early-onset cancer rates among younger individuals? A recent study conducted at the Washington University School of Medicine in St. Louis (WUSTL) claims the condition may be partially to blame for the increase in cancer diagnoses among young people. But what is accelerated aging, and what tests will clinical laboratories be required to perform to help physicians diagnose early-onset cancer in that age group?
“Accelerated aging—when someone’s biological age [how old one’s cells are] is greater than their chronological age [how long one has existed]—could increase the risk of cancer tumors,” Fox News reported.
In their presentation at the 2024 American Association for Cancer Research (AACR) annual meeting, the WUSTL researchers noted that “individuals born in or after 1965 had a 17% higher likelihood of accelerated aging than those born between 1950 and 1954,” according to an AACR news release.
The scientists studied “the association between accelerated aging and the risk of early-onset cancers,” and found that “each standard deviation increase in accelerated aging was associated with a 42% increased risk of early-onset lung cancer, a 22% increased risk of early-onset gastrointestinal cancer, and a 36% increased risk of early-onset uterine cancer.”
“Multiple cancer types are becoming increasingly common among younger adults in the United States and globally,” said Ruiyi Tian, MPH, a PhD candidate at WUSTL, in the news release. “Understanding the factors driving this increase will be key to improve the prevention or early detection of cancers in younger and future generations.”
Tian was part of the team conducting the study at the Cao Lab at WUSTL. The primary function of this lab is to uncover risk factors for various cancers and develop precision medicine protocols for cancer prevention and treatment.
“Historically, both cancer and aging have been viewed primarily as concerns for older populations,” Ruiyi Tian, MPH (above), a graduate student at Washington University School of Medicine in St. Louis and one of the study’s researchers, told Fox News. “The realization that cancer, and now aging, are becoming significant issues for younger demographics over the past decades was unexpected.” Clinical laboratories and anatomic pathologists will likely be performing cancer testing on younger populations as incidences of early-onset cancer increase. (Photo copyright: Washington University School of Medicine in St. Louis.)
The WUSTL researchers set out to prove that both chronological age and biological age could be determining factors in early-onset cancers. Chronological age refers to the amount of time an individual has been alive, while biological age refers to the age of cells and tissues based on physiological evidence.
“We all know cancer is an aging disease. However, it is really coming to a younger population,” said Yin Cao, MPH, Associate Professor of Surgery at WUSTL and senior author of the study, told CNN. “So, whether we can use the well-developed concept of biological aging to apply that to the younger generation is a really untouched area.”
To perform the research, the scientists examined data of 148,724 individuals between the ages of 37 and 54 located in the UK Biobank database. They calculated each person’s biological age by examining nine biomarkers found in blood:
They then input the data into the PhenoAge algorithm which estimated the biological age of each person.
“Individuals whose biological age was higher than their chronological age were defined as having accelerated aging,” the AACR news release noted.
The next step was to calculate each person’s level of accelerated aging by comparing biological and chronological ages. They then looked at how many of the individuals studied had been diagnosed with early-onset cancers.
For the WUSTL study, early-onset cancers were defined as cancers that were diagnosed before age 55. The researchers found 3,200 cases where such cancers had been discovered.
Faster Agers Twice as Likely to Develop Early-onset Cancer
The scientists then compared the data of people who showed slower aging to those showing faster aging based on the biobank samples. They found that individuals who had the highest accelerated aging were twice as likely to be diagnosed with early-onset lung cancer, had a 60% higher risk of gastrointestinal tumors, and had a more than 80% higher risk of uterine cancer.
“By examining the relationship between accelerating aging and the risk of early-onset cancers, we provide a fresh perspective on the shared etiology of early-onset cancers,” Tian said in the news release. “If validated, our findings suggest that interventions to slow biological aging could be a new avenue for cancer prevention, and screening efforts tailored to younger individuals with signs of accelerated aging could help detect cancers early.”
More clinical studies and research are needed to determine if accelerated aging truly is causing a rise in early-onset cancers. The fact that all of the participants in this study were from the United Kingdom indicates that future studies should include more diverse populations.
Studying accelerated aging’s influence on early-onset cancer may lead to new biomarkers that clinical laboratories and anatomic pathologists can use to help physicians diagnose the condition. Laboratory scientists and pathologists will want to follow any ongoing research and studies on the trend, as ‘accelerated aging’ might be identified as a new disorder to look for when diagnosing and treating cancers.
University of Cincinnati researchers hypothesize that low levels of amyloid-beta protein, not amyloid plaques, are to blame
New research from the University of Cincinnati (UC) and Karolinska Institute in Sweden challenges the prevailing theory about the causes of Alzheimer’s disease, suggesting the possibility of new avenues for the development of effective clinical laboratory assays, as well as effective therapies for treating patients diagnosed with Alzheimer’s.
Scientists have long theorized that the disease is caused by a buildup of amyloid plaques in the brain. These plaques are hardened forms of the amyloid-beta protein, according to a UC news story.
“The paradox is that so many of us accrue plaques in our brains as we age, and yet so few of us with plaques go on to develop dementia,” said Alberto Espay, MD, one of the lead researchers of the study, in another UC news story. Espay is Professor of Neurology at the UC College of Medicine and Director and Endowed Chair of the Gardner Center for Parkinson’s Disease and Movement Disorders.
“Yet the plaques remain the center of our attention as it relates to biomarker development and therapeutic strategies,” he added.
“It’s only too logical, if you are detached from the biases that we’ve created for too long, that a neurodegenerative process is caused by something we lose, amyloid-beta, rather than something we gain, amyloid plaques,” said Alberto Espay, MD (above), in a University of Cincinnati news story. “Degeneration is a process of loss, and what we lose turns out to be much more important.” The UC study could lead to new clinical laboratory diagnostics, as well as treatments for Alzheimer’s and Parkinson’s diseases. (Photo copyright: University of Cincinnati.)
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High Levels of Aβ42 Associated with Lower Dementia Risk
In their retrospective longitudinal study, the UC researchers looked at clinical assessments of individuals participating in the Dominantly Inherited Alzheimer Network (DIAN) cohort study. DIAN is an ongoing effort, sponsored by the Washington University School of Medicine in St. Louis, to identify biomarkers associated with Alzheimer’s among people who carry Alzheimer’s mutations.
The researchers found that study participants with high levels of a soluble amyloid-beta protein, Aβ42, were less likely to develop dementia than those with lower levels of the protein, regardless of the levels of amyloid plaques in their brains or the amount of tau protein—either as phosphorylated tau (p-tau) or total tau (t-tau)—in their cerebral spinal fluid. P-tau and t-tau are proteins that form “tau tangles” in the brain that are also associated with Alzheimer’s.
One limitation of the study was that the researchers were unable to include Aβ40, another amyloid-beta protein, in their analysis. But they noted that this “did not limit the testing of our hypothesis since Aβ40 exhibits lower fibrillogenicity and lesser depletion than Aβ42, and is therefore less relevant to the process of protein aggregation than Aβ42.” Fibrillogenicity, in this context, refers to the process by which the amyloid-beta protein hardens into plaque.
While the presence of plaques may be correlated with Alzheimer’s, “Espay and his colleagues hypothesized that plaques are simply a consequence of the levels of soluble amyloid-beta in the brain decreasing,” UC news stated. “These levels decrease because the normal protein, under situations of biological, metabolic, or infectious stress, transform into the abnormal amyloid plaques.”
The UC News story also noted that many attempts to develop therapeutics for Alzheimer’s have focused on reducing amyloid plaques, but “in some clinical trials that reduced the levels of soluble amyloid-beta, patients showed worsening in clinical outcomes.”
New Therapeutics for Multiple Neurodegenerative Diseases
Eisai, a Japanese pharmaceutical company, recently announced phase three clinical trial results of lecanemab, an experimental drug jointly developed by Eisai and Biogen, claiming that the experimental Alzheimer’s drug modestly reduced cognitive decline in early-stage patients, according to NBC News.
Espay noted that lecanemab “does something that most other anti-amyloid treatments don’t do in addition to reducing amyloid: it increases the levels of the soluble amyloid-beta.” That may slow the process of soluble proteins hardening into plaques.
Beyond their findings about Alzheimer’s, the researchers believe similar mechanisms could be at work in other neurodegenerative diseases such as Parkinson’s disease, where the soluble alpha-synuclein protein also hardens into deposits.
“We’re advocating that what may be more meaningful across all degenerative diseases is the loss of normal proteins rather than the measurable fraction of abnormal proteins,” Espay said. “The net effect is a loss not a gain of proteins as the brain continues to shrink as these diseases progress.”
Espay foresees two approaches to treating these diseases: Rescue medicine, perhaps based on increasing levels of important proteins, and precision medicine, which “entails going deeper to understand what is causing levels of soluble amyloid-beta to decrease in the first place, whether it is a virus, a toxin, a nanoparticle, or a biological or genetic process,” according to UC News. “If the root cause is addressed, the levels of the protein wouldn’t need to be boosted because there would be no transformation from soluble, normal proteins to amyloid plaques.”
Clinical Laboratory Impact
What does this mean for clinical laboratories engaged in treatment of both Alzheimer’s and Parkinson’s patients? A new understanding of the disease would create “the opportunity to identify new biomarkers and create new clinical laboratory tests that may help diagnose Alzheimer’s earlier in the disease progression, along with tests that help with the patient’s prognosis and monitoring his or her progression,” said Robert Michel, Editor-in-Chief of Dark Daily and its sister publication The Dark Report.
Given the incidence of Alzheimer’s disease in the population, any clinical laboratory test cleared by the FDA would be a frequently-ordered assay, Michel noted. It also would create the opportunity for pathologists and clinical laboratories to provide valuable interpretation about the test results to the ordering physicians.
Proof-of-concept research investigates whether photoacoustic imaging can be used in place of traditional tissue staining procedures during cancer surgery to determine if all of the tumor has been removed
Determining where breast cancer ends and healthy tissue begins is a critical part of breast cancer surgery. Surgeons are used to working closely during surgery with anatomic pathologists who generate pathology reports that specify the surgical or tumor margin, an area of healthy tissue surrounding a tumor that also must be excised to ensure none of the tumor is left behind. This helps prevent the need for follow-up surgeries and involves quick work on the part of medical laboratories.
Thus, any technology that renders such a pathology report unnecessary, though a boon to surgeons and patients, would impact labs and pathology groups. However, such a technology may soon exist for surgeons to use during breast cancer surgery.
Assessing Tumor Margin with Light During Surgery
A proof-of-concept study undertaken by researchers at Washington University School of Medicine in St. Louis (WUSTL) and California Institute of Technology (Caltech) has been looking at ways photoacoustic and microscopy technologies could enable surgeons to quickly and accurately assess the tumor margin during breast cancer surgeries. The research suggests it could be possible for surgeons to get answers about critical breast tumor margins without employing a clinical laboratory test.
This new technique based on light and sound uses photoacoustic imaging. The researchers scanned a tumor sample and produced images with enough detail to show whether the tumor was completely removed during surgery, a WUSTL news release explained.
The researchers scanned slices of tumors secured from three breast cancer patients. They also compared their results to stained specimens.
The photoacoustic images matched the stained samples in key features, according to the WUSTL news release. And the new technology produced answers in less time than standard analysis techniques. But more research is needed before photoacoustic imaging is used during surgeries, researchers noted.
“This is proof of concept that we can use photoacoustic imaging on breast tissue and get images that look similar to traditional staining methods without any sort of tissue processing,” Novack added.
A new imaging technique based on light and sound produces images doctors can use to distinguish cancerous breast tissue (below the dotted blue line) from normal tissue more quickly than is currently possible. The new technique (right) produces images as detailed and accurate as traditional methods (left) but in less time, according to the researchers. If such technology were eventually approved for clinical use, it would reduce the need for pathologists to analyze frozen sections while a patient was still in surgery. (Caption and photo copyright: WUSTL/Terence T. W. Wong.)
Once ready, this technology may well change how surgeons and pathologists collaborate to treat breast cancer patients and those with other chronic diseases that include growths that must be excised from the body.
Current Pathology Procedures Take Time, Not Always Useful During Cancer Surgery
At present, standard breast cancer operation procedures involve surgical and pathology teams working simultaneously while the breast cancer patient is in surgery.
Excised tissue is frozen (surrounded by a polyethylene glycol solution), sliced into wafers, stained with a dye, and microscopically analyzed by the pathologist in the clinical laboratory to determine if all cancerous tissue has been removed by the surgeon.
“The procedure takes about 10 to 20 minutes. However, freezing of tissue can result in some distortion of cells and some staining artifact. That is why frozen sections are often preliminary—with a final diagnosis based on routine processing of tissue,” according to LabTestsOnline.
Additionally, fatty breast specimens do not make good frozen sections, which requires surgeons to complete procedures uncertain about whether they removed all of the cancer, the researchers noted.
“Right now, we don’t have a good method to assess margins during breast cancer surgeries,” stated Rebecca Aft, MD, PhD, Professor of Surgery at WUSTL and co-senior study author.
Up to 60% of Breast Cancer Patients Require Follow-up Surgeries
More than 250,000 people in the US are diagnosed with breast cancer each year, and about 180,000 elect to undergo surgery to remove the cancer and preserve healthy breast tissue, WUSTL reported. However, between 20% to 60% of patients learn later they need more surgery to have additional tissue removed when follow-up lab analyses suggest tumor cells were evident on the surface of a tissue sample, Caltech noted in a news release.
“What if we could get rid of the waiting? With three-dimensional photoacoustic microscopy, we could analyze the tumor right in the operating room and know immediately whether more tissue needs to be removed,” noted Lihong Wang, PhD, Professor of Medical Engineering and Electrical Engineering in Caltech’s Division of Engineering and Applied Science. Wang conducted research when he was a Professor of Biomedical Engineering at University of Washington’s School of Engineering and Applied Science.
“Currently, no intraoperative tools can microscopically analyze the entire lumpectomy specimen. To address this critical need, we have laid the foundation for the development of a device that could allow accurate intraoperative margin assessment,” the study authors penned in Science Advances.
What is Photoacoustic Imaging and How Does it Work?
Photoacoustic imaging’s laser pulses create acoustic waves within tissue, which make way for intraoperative images with enough detail to expose cancerous tissue as compared to healthy tissue, explained a Medgadget article.
The graphic above shows elements of the photoacoustic microscopy system for surgical margin imaging developed by researchers at University of Washington School of Medicine in St. Louis and California Institute of Technology. (Photo Credit: Science Advances)
According to the Caltech news release:
· Photoacoustic imaging (also called photoacoustic microscopy or PAM by the researchers) employs a low energy laser that vibrates a tissue sample;
· Researchers measure ultrasonic waves emitted by the vibrating tissue;
· Photoacoustic microscopy reveals the size of nuclei, which vibrate more intensely than nearby material;
· Larger nuclei and densely packed cells characterize cancer tissue.
“It’s the pattern of cells—their growth pattern, their size, their relationship to one another—that tells us if this is normal tissue or something malignant,” said Deborah Novack, MD, PhD, WUSTL Associate Professor of Medicine, Pathology, and Immunology, and co-senior author on the study.
Whether in surgical suites or emergency departments, technological advancements continue to bring critical information to healthcare providers at the point of care, bypassing traditional medical laboratory procedures that cost more and take longer to return answers. Successful development of this technology would create new clinical collaborations between surgeons and anatomic pathologists while improving patient care.
