Tag: biomarkers

Who will Live to 100?

Photo by Ravi Patel on Unsplash

Those who wish to live to 100 cannot rely on chance. Instead, it is essential to keep biomarkers associated with ageing and disease in check. By the age of 60, it may already be too late.

Text by: Maja Lundbäck, first published in Medical Science No 3 2024

Swedes are increasingly living to older ages. Thirty years ago, 85-90- year-olds were rare, but now the majority reach that age ‒ and two percent even get to see 100 candles on their birthday cake.

“Centenarians are the age group that is increasing the most now,” says Karin Modig, Associate Professor at the Institute of Environmental Medicine at Karolinska Institutet, who researches ageing and health.

In a study published in the journal GeroScience, she and her colleagues show that it is possible to predict who has the greatest chance of becoming very old already during early ageing. The study is based on approximately 44 000 Swedes who underwent health examinations between 1985 and 1996, aged between 64 and 99. Of these, 1224 individuals lived to 100.

“The results suggest that becoming very old is not solely a matter of chance; it also seems to be linked to lifestyle,” says Karin Modig.

Known biomarkers 

By looking at known biomarkers previously associated with ageing and disease, the researchers found that the centenarians had better health than their peers already in their 60s. All but two of twelve biomarkers examined could be linked to increased chances of reaching 100 years. Low iron levels reduce the chance, as does low total cholesterol, which can be a marker of disease processes in the body.

Four of the biomarkers stood out as particularly important: creatinine levels, which indicate kidneys health, were almost always normal at age 60 in those who lived to 100. The same was true for liver markers and uric acid levels, a marker for inflammatory processes. Individuals with the lowest uric acid levels had a four percent chance of living to 100, while those with the highest levels had a 1.5 percent chance. Blood sugar levels were also rarely above 6.5mmol/litrw.

The results suggest that it may be possible to increase one’s chances of living to 100 by changing your lifestyle, she believes.

“At the same time, life is not about living according to an algorithm; everyone must find their own balance between risk factors and health factors,’ she says.

Source: Karolinska Institutet

New Biomarker Database for Astronaut Health may be Useful to Earthlings

Photo: Pixabay CC0

As space travel becomes more frequent, a new biomarker tool was developed by an international team of researchers to help improve the growing field of aerospace medicine and the health of astronauts.

Dr Guy Trudel (Professor in the Faculty of Medicine), Odette Laneuville (Associate Professor, Faculty of Science, and Director of the Biomedical Sciences) and Dr Martin Pelchat (Associate Professor in the Department of Biochemistry, Microbiology and Immunology) are among the contributors to an international study led by Eliah Overbey of Weill Cornell Medicine and the University of Austin. Published today in Nature it introduces the Space Omics and Medical Atlas (SOMA), a database of integrated data and sample repository from a diverse range of space missions, including from SpaceX and NASA.

Space travel creates cellular, molecular, and physiological shifts in astronauts. SOMA is expected to provide a much necessary biomedical profiling that can help tease out the short and long-term health impacts of spaceflight. This will bring needed health monitoring, risk mitigation, and countermeasures baseline data for upcoming lunar, Mars, and exploration-class missions. It is meant to help keep astronauts and space travellers alive and healthy.

It may also have some intended use here on Earth.

“This represents a breakthrough in the study of human adaptation and life in space. Since many of the changes in astronaut in space resemble those of people who are immobile in bed, these studies can be clinically relevant. The data are therefore important for future space exploration while also providing a correlation to people on Earth with limited mobility or who are bedridden before their rehabilitation,” says Dr Trudel, a rehabilitation physician and researcher at The Ottawa Hospital who has focused on space travel and its effects on the human immune system.

Highlights of the study, include:

  • The Atlas includes extensive molecular and physiological profiles encompassing genomics, epigenomics, transcriptomics, proteomics, metabolomics, and microbiome data sets, which reveal some consistent features across missions.
  • Samples were taken pre-flight, during, post-flight and throughout the recovery period.
  • Comprehensive profile of the physiological changes of the I4 crew (ages 29, 38, 42, 51) and 13 unique biospecimen sample types were collected and processed.
  • 2911 samples were banked with over 1000 samples processed for sequencing, imaging, and biochemical analysis creating the first-ever aerospace medicine biobank.
  • The SOMA resource represents an over 10-fold increase in total publicly available human space omics data.

“The University of Ottawa’s Faculty of Medicine, its Faculty of Science, and The Ottawa Hospital’s Bone and Joint Research laboratory have a long history of contributions and successes in studying human adaptation to space. They also involve students from different programs, providing a unique learning experience in both bone and joint health, and in the rapidly developing field of aerospace medicine,” adds Dr Trudel.

Source: University of Ottawa

New, More Accurate Approach to Blood Tests for Determining Diabetes Risks

Photo by National Cancer Institute on Unsplash

A new approach to blood tests could potentially be used to estimate a patient’s risk of type 2 diabetes, according to a new study appearing in BMC’s Journal of Translational Medicine. Currently, the most commonly used inflammatory biomarker currently used to predict the risk of type 2 diabetes is high-sensitivity C-reactive protein (CRP). But new research has suggested that jointly assessing of biomarkers, rather than assessing each individually, would improve the chances of predicting diabetes risk and diabetic complications.

A study by Edith Cowan University (ECU) researcher Dan Wu investigated the connection between systematic inflammation, assessed by joint cumulative high-sensitivity CRP and another biomarker called monocyte to high-density lipoprotein ratio (MHR), and incident type 2 diabetes.

The study followed more than 40 800 non-diabetic participants over a near ten-year period, with more than 4800 of the participants developing diabetes over this period.

Wu said that of those patients presenting with type 2 diabetes, significant interaction between MHR and CRP was observed.

“Specifically, increases in the MHR in each CRP stratum increased the risk of type 2 diabetes; concomitant increases in MHR and CRP presented significantly higher incidence rates and risks of diabetes.

“Furthermore, the association between chronic inflammation (reflected by the joint cumulative MHR and CRP exposure) and incident diabetes was highly age- and sex-specific and influenced by hypertension, high cholesterol, or prediabetes. The addition of the MHR and CRP to the clinical risk model significantly improved the prediction of incident diabetes,” said Wu.

Biological sex a risk factor

The study found that females had a greater risk of type 2 diabetes conferred by joint increases in CRP and MHR, with Wu stating that sex hormones could account for these differences.

Wu said that the research findings corroborated the involvement of chronic inflammation in causing early-onset diabetes and merited specific attention.

“Epidemiological evidence indicates a consistent increase in early-onset diabetes, especially in developing countries. Leveraging this age-specific association between chronic inflammation and type 2 diabetes may be a promising method for achieving early identification of at-risk young adults and developing personalised interventions,” she added.

Wu noted that the chronic progressive nature of diabetes and the enormous burden of subsequent comorbidities further highlighted the urgent need to address this critical health issue.

Although aging and genetics are non-modifiable risk factors, other risk factors could be modified through lifestyle changes.

Inflammation is strongly influenced by life activities and metabolic conditions such as diet, sleep disruptions, chronic stress, and glucose and cholesterol dysregulation, thereby indicating the potential benefits of monitoring risk-related metabolic conditions.

Wu said that the dual advantages of cost effectiveness and the wide availability of cumulative MHR and CRP in current clinical settings, potentiated the widespread use of these measures as a convenient tool for predicting the risk of diabetes.

Source: Edith Cowan University

Wearable Device may Detect Skin Electrical Impulses Associated with Mood Changes in Bipolar Disorder

Researchers have used wearable technology to measure electrical impulses in the skin and other physiological biomarkers possibly linked to mood changes in bipolar disorder. Though at an early stage, they hope their work will be able to build on these patterns to detect mood swings in bipolar disorder sufferers, so helping in diagnosis and potentially offering more rapid and personalised treatments. They presented their research at the 36th ECNP Congress in Barcelona, and more information is available on GitHub.

Bipolar disorder (formerly called manic-depressive illness or manic depression) is a mental illness that causes swings in a person’s mood, energy, activity levels, and concentration. These shifts can make it difficult to carry out day-to-day tasks and can make interactions with other people difficult. The degree of mood swing can vary from person to person, from feeling manic (very “up”) to feeling depressed. At present, these mood swings are mostly diagnosed subjectively, through interview with doctors or by questionnaires. This takes time, and requires an immediate medical presence.

Now a group of Barcelona-based psychiatrists, in collaboration with data scientist in Edinburgh, have used a research grade wearable device to continuously collect several physiological biomarkers during the diverse phases and episodes of bipolar disorder. Among the collected physiological biomarkers is electrodermal activity which uses changes in the skin’s electrical conductivity to indicate the level of stress through the reactivity of the nervous system. This is a potential immediate indicator of whether someone is in a manic, depressive or in a normal mood state.

They recruited 38 patients with bipolar disorder, and 19 healthy controls, all from the Barcelona area.

Researcher Diego Hidalgo-Mazzei said “Each participant was fitted with a commercially available Empatica E4 bracelet, which they were asked to wear for around 48 hours. This can measure a variety of physiological changes, but we were most interested in measuring small electrophysiological changes in the skin of the wearer. We found that bipolar disorder patients in their depressed phase had on average a significantly lower skin electrical activity than the rest of the bipolar group or the healthy control group. We also found that as an individual moved from manic to depressive state (or vice versa), this was detectable by a change in skin surface electrical activity.

“It is important for the patient and doctor to know how and when these mood fluctuations take place. It is important also to highlight that the treatment is different for manic or depressive states. This can help with a prompt diagnosis and early personalized treatment, but it can also help in preventing adverse outcomes, for example in alerting to an increased risk of suicide, or of mood swings which may lead to dangers with activities such as driving. It is also easier to treat patients if we know if they are in a manic phase or a depressed phase. Until now, these mood swings have mostly been diagnosed subjectively, through interview with doctors or by questionnaires, and this had led to real difficulties. Arriving at the correct drug is difficult, with only around 30 to 40% of treated individuals having the expected response. We hope that the additional information these systems can provide will give us greater certainty in treating patients.

“We are still some way from that though. This is an exploratory observational study, so we need to look at a larger sample and use machine learning to analyse all the biomarkers collected by the wearers to confirm the findings to determine patterns which might indicate a specific episode. This may not be ideal for every bipolar disorder sufferer, in every circumstance, but a potential pattern may help in the future the people hardest hit by the mood changes which affect their lives”.

For information on the wearable device see https://e4.empatica.com/e4-wristband

Source: EurekAlert!

Can We Predict the Severity of Food Allergies Using Genetics?

Photo by Sangharsh Lohakare on Unsplash

Researchers have discovered that a genetic biomarker may be able to help predict the severity of food allergy reactions. Currently there is no reliable or readily available clinical biomarker that accurately distinguishes patients with food allergies who are at risk for severe life-threatening reactions versus more mild symptoms. The researchers reported their findings in the Journal of Allergy and Clinical Immunology.

The researchers, led by Ann & Robert H. Lurie Children’s Hospital of Chicago, found that the presence of an enzyme isoform called α-tryptase, which is encoded by the TPSAB1 gene, correlates with increased prevalence of anaphylaxis or severe reaction to food as compared to subjects without any α-tryptase.

“Determining whether or not a patient with food allergies has α-tryptase can easily be done in clinical practice using a commercially available test to perform genetic sequencing from cheek swabs,” said lead author Abigail Lang, MD, MSc, attending physician and researcher at Lurie Children’s and Assistant Professor of Pediatrics at Northwestern University Feinberg School of Medicine. “If the biomarker is detected, this may help us understand that the child is at a higher risk for a severe reaction or anaphylaxis from their food allergy and should use their epinephrine auto-injector if exposed to the allergen. Our findings also open the door to developing an entirely new treatment strategy for food allergies that would target or block α-tryptase. This is an exciting first step and more research is needed.”

Tryptase is found mainly in mast cells, which become activated during allergic reactions. Increased TPSAB1 copy number which leads to increased α-tryptase is already known to be associated with severe reactions in adults with Hymenoptera venom allergy (or anaphylaxis following a bee sting).

Dr Lang’s study included 119 participants who underwent TPSAB1 genotyping, 82 from an observational food allergy cohort at the National Institute of Allergy and Infectious Diseases (NIAID) and 37 from a cohort of children who reacted to peanut oral food challenge at Lurie Children’s.

“We need to validate our preliminary findings in a much larger study, but these initial results are promising,” says Dr Lang. “We also still need a better understanding of why and how α-tryptase makes food allergy reactions more severe in order to pursue this avenue for potential treatment.”

Source: Ann & Robert H. Lurie Children’s Hospital of Chicago

Studies Point to New, Better Ways to Monitor Head and Neck Cancer Recurrence

Photo by National Cancer Institute on Unsplash

Early findings of a pair of studies from the University of Michigan Rogel Cancer Center shed light on new ways to anticipate recurrence in HPV-positive head and neck cancer sooner. The papers, published in Cancer and Oral Oncology, offer clinical and technological perspectives on how to measure if recurrence is happening earlier than current blood tests allow, and provide a framework for a new, more sensitive blood test that could help in this monitoring.

“When metastatic head and neck cancer returns, it impacts their quality of life and can be disfiguring, interfering with the ability to talk, swallow, and even breathe,” said Paul Swiecicki, MD, associate medical director for the Oncology Clinical Trials Support Unit at Rogel. “As of now, there’s no test to monitor for its recurrence except watching for symptoms or potentially using a blood test which may not detect cancer until shortly before it clinically recurs.”

The paper in Cancer aims to identify different clinical ways that providers can more strategically track for recurrence. To do this, Swiecicki and his team needed to first understand what patient population was at the highest risk to then figure out an appropriate monitoring pattern.

The team examined 450 patients with metastatic head and neck cancer, including people with HPV-positive and HPV-negative cancer. HPV-positive cancer is caused by the human papillomavirus and is increasingly more common in head and neck cancer patients. The team identified some predictors of when recurrences would happen, and to what organs the recurrent cancer would most commonly spread. Patients with HPV-positive cancers were found to develop recurrent disease significantly later than those that were HPV-negative, and also were more likely to spread to the lungs. Taken together, these characteristics may help create a “surveillance” method in the future that combines routine blood testing and imaging to hopefully catch these recurrences and intervene before it’s incurable.

Swiecicki is quick to mention that, at this point, the results of this study are largely theoretical and provide a helpful framework to direct further research. That’s where the newly developed blood test, highlighted in Oral Oncology, comes into play.

Current blood biomarker tests which test for pieces of tumour-shed DNA, may not be sensitive enough to detect a recurrence significantly earlier than clinical surveillance, though several studies with multiple types of tests are ongoing. A research team, led by Muneesh Tewari, MD, PhD, Swiecicki and Chad Brenner, PhD, aimed to create a highly sensitive blood test to detect cancer even when a smaller number of DNA fragments were present, with the intention of providing a better option for detecting cancer earlier in patients.

Not only is this test more sensitive and able to detect a smaller number of DNA fragments in blood, but it’s innovative in other ways too, says first author Chandan Bhambhani, PhD: “We achieved this level of sensitivity by looking for nine different pieces of the HPV genome DNA all at once,” Bhambhani says.

Tewari says this is a step towards a more proactive approach to tackling recurrence in head and neck cancer. “As of now, we only have the tools to react to symptoms when they recur. We want to find a way to be able to detect what’s causing the symptoms much, much sooner, even before the symptoms appear.”

As a clinician, Swiecicki agrees. “It’s exciting to have the ability to potentially detect cancer before it’s incurable and offer us a window for clinical trials to see if we could intervene on cancer to help give people both a better quality of life and perhaps longer quality of life, and even convert their disease from incurable to curable. We don’t know if that’s the case yet, but this is the first tool needed for that to develop.”

Source: Michigan Medicine – University of Michigan

Plasma Protein Biomarkers Could Detect Early Mental Health Problems in Adolescents

Photo by Andrew Neel on Unsplash

Researchers at the University of Eastern Finland have identified plasma protein-based biomarkers capable of identifying adolescents at risk of developing mental health issues. Such biomarkers could revolutionise early detection and prevention of mental health problems in young people.The results were published in Nature Mental Health.

Some 10–20% of adolescents struggle with mental health conditions, with the majority going undiagnosed and untreated. This points to a need for new, early indicators of mental health problems to catch these cases and intervene with treatment before the conditions progress.

In the study carried out in the research group of Professor Katja Kanninen, the researchers used self-reported Strengths and Difficulties Questionnaire (SDQ) scores to evaluate mental health risk in participants aged between 11 and 16 years. Blood sample analyses showed that 58 proteins were significantly associated with the SDQ score. Bioinformatic analyses were used to identify the biological processes and pathways linked with the identified plasma protein biomarker candidates. Key enriched pathways related to these proteins included immune responses, blood coagulation, neurogenesis, and neuronal degeneration. The study employed a novel symbolic regression algorithm to create predictive models that best separate low and high SDQ score groups.

According to Professor Kanninen, plasma biomarker studies in mental disorders are an emerging field.

“Alterations in plasma proteins have been previously associated with various mental health disorders, such as depression, schizophrenia, psychotic disorders, and bipolar disorders. Our study supports these earlier findings and further revealed that specific plasma protein alterations could indicate a high risk for mental dysfunction in adolescents,” Professor Kanninen notes.

According to the researchers, this pilot study will be followed by more specific investigations of the potential biomarkers for identification of individuals at risk of mental health problems, opening a new avenue for advancements in adolescent mental health care.

Source: University of Eastern Finland

A Quick and Inexpensive Test for Osteoporosis

Photo by Mehmet Turgut Kirkgoz on Unsplash

In osteoporosis, treatment would be most effective with early detection – something not yet possible with current X-ray based osteoporosis diagnostic tests, which lack the requisite sensitivity. Now, researchers reporting in ACS Central Science have developed a biosensor that could someday help identify those most at risk for osteoporosis using less than a drop of blood.

Early intervention is critical to reducing the morbidity and mortality associated with osteoporosis. The most common technique used to measure changes in bone mineral density (BMD) – dual-energy X-ray absorptiometry – is not sensitive enough to detect BMD loss until a significant amount of damage has already occurred. Several genomic studies, however, have reported genetic variations known as single nucleotide polymorphisms (SNPs) that are associated with increased risk for osteoporosis. Using this information, Ciara K. O’Sullivan and colleagues wanted to develop a portable electrochemical device that would allow them to quickly detect five of these SNPs in finger-prick blood samples in a step toward early diagnosis.

The device involves an electrode array to which DNA fragments for each SNP are attached. When lysed whole blood is applied to the array, any DNA matching the SNPs binds the sequences and is amplified with recombinase polymerase that incorporates ferrocene, a label that facilitates electrochemical detection. Using this platform, the researchers detected osteoporosis-associated SNPs in 15 human blood samples, confirming their results with other methods.

As the DNA does not have to be purified from the blood, the analysis can be performed quickly (about 15 minutes) and inexpensively (< $0.5 per SNP). Furthermore, because the equipment and reagents are readily accessible and portable, the researchers say that the device offers great potential for use at point-of-care settings, rather than being limited to a centralised laboratory. The technology is also versatile and can be readily adapted to detect other SNPs, as the researchers showed previously when identifying drug resistance in Tuberculosis mycobacterium from sputum and cardiomyopathy risk from blood. Although the device does not diagnose osteoporosis itself, it might help physicians identify people whom they should monitor more closely.

Source: Chemical Society

Researchers Discover a Lipid Biomarker that can Identify Preeclampsia Risk

Photo by Shvets Production on Pexels

University of Virginia School of Medicine researchers have discovered a lipid biomarker to identify pregnant women at risk of preeclampsia, complications from which are the second-leading cause of maternal death around the world. Their findings are published in the Journal of Lipid Research.

The UVA scientists, led by Charles E. Chalfant, PhD, say that their finding opens the door to simple blood tests to screen patients. Further, the approach worked regardless of whether the women were on aspirin therapy, which is commonly prescribed to women thought to be at risk.

“Clinicians have been seeking simple tests to predict risk of preeclampsia before symptoms appear. Although alterations in some blood lipid levels have been known to occur in preeclampsia, they have not been endorsed as useful biomarkers. Our study presents the first comprehensive analysis of lipid species, yielding a distinctive profile associated with the development of preeclampsia,” said Chalfant. “The lipid ‘signature’ we described could significantly improve the ability to identify patients needing preventative treatment, like aspirin, or more careful monitoring for early signs of disease so that treatment could be initiated in a timely fashion.”

Preeclampsia affects up to 7% of all pregnancies. Symptoms typically appear after 20 weeks and include high blood pressure, kidney problems and abnormalties in blood clotting. The condition is associated with dangerous complications such as kidney and liver dysfunction and seizures, as well as a lifelong increased risk of heart disease for the mothers. An estimated 70 000 women around the world die from preeclampsia and its complications each year.

Doctors commonly recommend low-dose aspirin for at-risk women, but it works for only about half of patients, and it needs to be started within the first 16 weeks of pregnancy – well before symptoms appear. That makes it all the more important to identify women at risk early on, and to better understand preeclampsia in general.

Chalfant and his team wanted to find ‘biomarkers’ in the blood of pregnant women that could reveal their risk of developing preeclampsia. They examined blood plasma samples collected from 57 women in their first 24 weeks of pregnancy, then looked at whether the women went on to develop preeclampsia. The researchers found significant differences in ‘bioactive’ lipids in the blood of women who developed preeclampsia and those who did not.

This, the researchers say, should allow doctors to stratify women’s risk of developing preeclampsia by measuring lipid changes in their blood. The changes represent an important ‘lipid fingerprint’, the scientists say, that could be a useful tool for identifying, preventing and better treating preeclampsia.

“The application of our comprehensive lipid profiling method to routine obstetrical care could significantly reduce maternal and neonatal morbidity and mortality,” Chalfant said. “It represents an example of how personalised medicine could address a significant public health challenge.”

Source: University of Virginia Health System

Neuroimaging can’t Identify Psychiatric Disorders – Yet

MRI images of the brain
Photo by Anna Shvets on Pexels

Neuroimaging technologies hold great promise in helping clinicians link specific symptoms of mental health disorders to abnormal patterns of brain activity. But a new study published in the American Journal of Psychiatry shows there are still kinks to be ironed out before doctors can translate images of the brain to psychiatric disorders such as post-traumatic stress disorder (PTSD).

Several years ago, The National Institutes of Mental Health launched a multi-billion-dollar research effort to locate biomarkers of brain activity that point to the biological roots of a host of mental health diseases, which today are typically identified by clinical evaluation of a constellation of often overlapping symptoms reported by patients.

“The idea is to forget classification of disease by symptoms and find underlying biological causes,” said Yale’s Ilan Harpaz-Rotem, professor of psychiatry and psychology and senior author of the study.

For the new study, the Yale-led team attempted to replicate the findings of an earlier nationwide neuroimaging study, in which scientists linked clusters of brain activity to a variety of outcomes among patients who had arrived at US emergency departments following traumatic events. Specifically, when researchers measured patients’ brain activity during the performance of simple tasks such as mapping responses to threats and rewards, they detected a cluster of brain activity that showed high reactivity to both threat and reward signals and seemed to predict more severe symptoms of PTSD later on.

However, when Yale researchers analysed similar neuroimaging data collected from recent trauma survivors in Israel, they were not able to replicate these findings. While they did identify the different clusters of brain activity observed in the earlier study, they found no association with prospective PTSD symptoms.

“That is not to say one set of data is right and the other is wrong, just that there is a lot of fundamental work that needs to be done to develop reliable models that could generalise across different studies,” said Yale’s Ziv Ben-Zion, a postdoctoral associate at Yale School of Medicine and the corresponding author of the study.

In fact, Yale researchers are currently working with the investigators of the original study to merge datasets “to search for common underlying patterns of brain activity associated with different responses to trauma,” Ben-Zion said.

“It took about 100 years to come up with current classifications of mental illness, but we’ve only been exploring refining psychiatric diagnoses using biomarkers for the last 10 years,” said Harpaz-Rotem. “We still have a long way to go.”

Source: Yale University