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What are biomarkers? A biologist explains how doctors measure your health – and how combining cells from different people can find new markers
Why are some people hit harder by certain diseases than others? Why do some patients respond better to a treatment, while others see no effect? Biomarkers can help answer these questions.
Octo Health Launches Beta to Make Proactive, Personalized Healthcare More Accessible
Octo Health brings medical records, lab results, medications and health data into one health timeline, giving consumers a more complete picture of their healthBy combining annual testing of more than 100 biomarkers with unified health data, the platform helps members identify patterns and track health trends over timeAs consumers take a more active role in managing their health, Octo Health gives them greater ownership of their data and helps them understand what it means NEW YORK, Nov. 05, 2026
Finding biomarkers for aggressive prostate cancer
Proteins linked to the immune system, cell adhesion, blood vessel formation, and known prostate cancer genes, were associated with the future risk of developing prostate cancer, including aggressive disease, in a new study led by researchers at Oxford Population Health.
Improving breast cancer treatment; improving prostate cancer diagnosis; listen to your knee pain; plus other stories with Vanderbilt Health sources
WTVF News Channel 5’s “Morningline” program interviewed Denise Garcia, MD, Assistant Professor of Surgery, about new technology that helps surgeons identify cancer during surgery and improve breast cancer treatment. A Men’s Health story about PSA screening for prostate cancer quoted Kelvin Moses, MD, PhD, Professor of Urology. Men’s Health posted a story, “What Your Knee Pain is Trying to Tell You,” that quotes Charles Cox, MD, MPH, Associate Professor of Orthopaedic Surgery. William Schaffner, MD, Professor of Preventive Medicine, was quoted by several news outlets about public health issues, including: WSMV Channel 4 News (importance of flu shots); MedPage Today (mRNA flu shots); WTVF News Channel 5 (19 people sent to hospital after a sickness outbreak at Walmart facility in Lebanon); Prevention (West Nile virus); HuffPost (prevention pill for COVID); and Newsweek (measles cases continue to increase in the U.S.). Becker’s Hospital Review and Nashville Post covered the Vanderbilt Health News story from Rebecca Warren that Chief Communications Officer John Howser is retiring in March 2027, closing out a nearly 40-year career at Vanderbilt. A Healio story on research about OCT-A biomarkers and diabetic retinopathy quotes Vanderbilt University School of Medicine student Rachel Liu. WPLN Nashville Public Radio quoted Amanda Mixon, MD, MPH, Associate Professor of Medicine, in a story about adverse drug interactions.
New Tools and Fresh Thinking Are Reshaping the Science of Addiction
A new Frontiers Research Topic argues that biosensors, longitudinal phenotyping, and transdiagnostic biomarkers are transforming addiction from a static label into a dynamic, mechanism-based science.
Science on Target: Q3 Research We Fund
$2.4 million Invested in Biomarker Innovation ALS is a heterogeneous disease with distinct subpopulations of cases clustering together based on common underlying biology and with distinct differences in the clinical time course and manifestation of disease. Biomarkers are therefore critical for enabling precision medicine to deliver the right therapy to the right individual at the […]
Yale School of Medicine On the Science of Childhood Anxiety, Say, Anxiety Disorders Are the Most Common Mental Health Challenges In Youth
Credit: Matt Bradbury October 5, 2026 - By Isabella Backman - Anxiety disorders are the most common mental health challenges in youth. Left untreated, they can disrupt the lives of both children and their families. The good news is that with intervention, most children will overcome these conditions. Across Yale School of Medicine, scientists are working to understand anxiety at every level, from common anxious behaviors to molecular biomarkers in the brain. They are using their findings to develop and disseminate new evidence-based treatments for childhood anxiety. Today, the go-to treatment for childhood anxiety disorders is cognitive behavioral therapy (CBT). This is a form of psychotherapy that teaches children skills for confronting anxious thoughts and helps them practice managing situations that cause anxiety. While it is the gold-standard treatment backed by considerable scientific evidence, up to 50% of children will not see sufficient benefit from CBT alone. Wendy Silverman, PhD, Alfred A. Messer Professor in the Child Study Center, co-directs the Anxiety and Mood Disorders Program alongside Eli Lebowitz, PhD, associate professor in the Child Study Center. One of their main interests is learning how to improve outcomes beyond CBT. “We’re developing cutting-edge, research-based knowledge that can reduce the suffering that anxiety causes children and their families,” says Silverman. Changing parent behavior YSM experts are investigating how to improve CBT outcomes for children by involving the parents. Silverman’s research has uncovered two main components of parent intervention that improve childhood anxiety: not enabling children to completely avoid the things that make them anxious and taking steps to enhance their autonomy. Parents may unintentionally reinforce their child’s anxiety by allowing them to avoid what makes them anxious. They also may unintentionally limit the children’s sense of autonomy by being overly intrusive. “One of the things that we take pride in is that we’ve focused on trying to understand what parents need to do, and to test our ideas and see if changing the parents’ behaviors is enhancing the effects of CBT,” Silverman says. “Our findings thus far suggest that they do." As much as CBT can be helpful, it can also be challenging to get one’s child to do the necessary steps for CBT to work. This is one important reason why Lebowitz created a novel intervention program for parents named Supportive Parenting for Anxious Childhood Emotions (SPACE). Existing intervention programs often teach parents to act as therapists for their child, such as training them on how to practice breathing exercises. “It makes sense, but this doesn’t work very well in practice,” says Lebowitz. “And part of the reason, I think, is that it’s not easy to get your kid to do things, especially if they’re not excited about doing it.” SPACE is unique because it focuses entirely on parent involvement and changing parental behavior—children are not involved in the sessions. For example, parents learn how to use supportive messages that convey confidence that their child can tolerate and manage distress. “It might sound like a parent saying to a child, ‘I get that this is really hard for you, but I know that you can handle it,’” Lebowitz says. The program also works with parents to identify the ways in which they are accommodating anxious behaviors. “We’ll pick one thing that parents are doing that is an accommodation and help them make a detailed plan for how they’re going to change that,” Lebowitz explains. Treating Anxiety in Children and Adolescents Much of the existing research on SPACE has focused on parents of children under age 14. Ongoing studies are now exploring its use with parents of older teens. “Both anxiety and accommodation can interfere with normative developmental shifts during the teen years, including increased autonomy and individuation from parents,” says Rebecca Etkin, PhD, associate research scientist in the Child Study Center. “In this sense, SPACE may be particularly well-suited for anxious teens and their parents. We want to see whether it is effective during this distinct developmental window.” Unfortunately, many families in need of CBT face barriers, including limited availability of services and geographic constraints. One way to improve access is digital interventions. Silverman and her team are developing an evidence-based digitized intervention program for parents that they can access directly from their computer or smart phone. “The work we’re doing will be one of the very few parent interventions that is digitized and importantly tested for effectiveness,” she says. Creating interventions for anxiety-related challenges Silverman and Lebowitz recently received a generous gift to develop and test other interventions that help parents reduce other child anxiety-related behavioral and emotional difficulties, such as restrictive eating and unexplained somatic symptoms. One of these projects in particular focuses on understanding the risks of social media and its potential benefits, including offering a sense of connection. “A lot of research has focused on the idea that social media is harmful and the less of it the better,” says Lebowitz. “But we actually see is that this is not quite right—there are negatives, but there are also positives. So, we’re trying to get a little bit more nuanced of a picture.” The team is working with teens with social anxiety and their parents over an extended period to better understand their social media habits and how their anxiety levels affect engagement with different platforms. The teens will answer questions sent to an app on their phones about mood and social media usage in an effort to capture emotional responses as they unfold. “We hope to develop interventions that can help make the best of social media while protecting against the more problematic effects,” Lebowitz says. The brain’s role in anxiety Researchers are also testing therapies to address anxiety at the neurological and molecular levels. In collaboration with Dylan Gee, PhD, professor of psychology in Yale's Faculty of Arts and Sciences, and Hilary Blumberg, MD, John and Hope Furth Professor of Psychiatric Neuroscience at Yale School of Medicine, Lebowitz and Silverman are using brain imaging to identify changes in a child’s brain before and after parents enroll in SPACE. In one study, children viewed anxiety-inducing images while undergoing magnetic resonance imaging (MRI); the researchers conducted scans with and without the children’s parents nearby. Before SPACE, children’s brains were better able to activate the regulatory circuitry needed to turn off an anxious response when their parents were nearby. But after SPACE, children could activate this circuitry even without the parent around. “As parents work on gradually reducing some of their accommodations, you can see a child get better at regulating their own fear system in the brain,” Lebowitz says. “It’s remarkable.” Research into the molecular underpinnings of anxiety can also inform new childhood anxiety treatments. In a recent study, Lebowitz, Silverman, and Flora Vaccarino, MD, Harris Professor in the Child Study Center, discovered that a protein known as fibroblast growth factor 2 (FGF2) could be protective from the toxic effects of stress. FGF2 levels in children and their parents were linked to the children’s risk of developing anxiety and depression, the study showed. The findings could help explain why some children who are exposed to early life trauma such as poverty or abuse are more prone to developing mental health disorders. And FGF2 could be a target for treatment. “This is very novel because it starts to give a clue to what is the molecular chain that connects those lived experiences to the actual psychological outcomes,” Lebowitz says. New ways to study and treat childhood anxiety Michael Crowley, PhD, associate professor in the Child Study Center, collaborates with Silverman and Lebowitz to study the role that attention plays in development and maintenance of childhood anxiety. There is a large body of research that shows that anxious children, like anxious adults, are prone to focus on threatening stimuli such as angry faces compared with neutral faces. This has led to innovative interventions that involve attention retraining. The idea is that if experts train children to look away from threatening stimuli, it may reduce their anxiety—especially children with social anxiety who are most prone to attend to threats. The researchers have just completed a clinical trial for attention retraining with 10- to 14-year-olds with social anxiety disorders and are currently analyzing the findings. Besides this innovative attention retraining research, as Crowly notes, “I like to design tasks that are engaging to kids,” Crowley says. “My goal is to assess something without the kids knowing what we are assessing.” With this goal in mind, Crowley has created a virtual game, named Boom, to study threat processing in children with anxiety disorders. The game is similar to that of hot potato—the child and three digital players take turns virtually passing a ball to each other’s gloves. At some point, the ball turns into a bomb, and as the bomb lands in each player’s glove, the outline of the glove turns yellow. The goal is to avoid having the bomb go off in your glove. What isn’t obvious is that the game is designed to measure different types of threatening stimuli, both ambiguous and direct. In the game, the direct threat occurs as the bomb is traveling towards your glove. The ambiguous threat is the yellow outlined glove as it is unknown where the bomb will travel next. While children play the game, Crowley’s team measures their brain activity using electroencephalography (EEG). The researchers have discovered that in kids with anxiety, the brain reacts more strongly to ambiguous threats than it does in their peers, but less strongly to direct threats. They believe that the initial abnormally large brain response to not knowing where the bomb is going impairs the brain's ability to properly respond when the threat is actually traveling the child’s way. “The brains of children with anxiety are unable to differentiate between threats you need to do something about and those that are not your problem.” Michael Crowley, PhD, develops innovative games for studying anxiety in children and adolescents.Credit: Matt Bradbury Based on these insights, Crowley hopes to study whether interventions like attention training could restore appropriate threat processing. Crowley’s team is also working on a test called the Balloon Risk Avoidance Task, which evaluates risk-taking and avoidance behaviors. It features a digital balloon that is full of air and about to burst. Kids have six seconds to let air out of the balloon. The more air they let out, the less risk they face that the balloon will pop. But at the same time, the balloon becomes less valuable as it deflates. “The more air you keep in the balloon, the more points you get,” Crowley explains. So far, the researchers have found that when the balloons pop unexpectedly, teens with social anxiety show distinct brain responses. Studying these responses can help psychologists understand the underlying pathways driving the various manifestations of anxiety. The genetics of anxiety When Thomas Fernandez, MD, associate professor in the Child Study Center and of psychiatry, was still in training, there was a lot of excitement about understanding the genetics associated with autism spectrum disorder. Since then, scientists have identified around 250 genes associated with autism. The genetic contribution to anxiety disorders, on the other hand, has historically received less attention. Anxiety is less heritable than autism, but the genetic contribution for anxiety disorders that emerge in childhood may be higher than for anxiety disorders overall. While scientists estimate the heritability of anxiety disorders in general to be around 30% to 50%, some studies suggest higher heritability for certain childhood-onset anxiety presentations. “I saw firsthand how researchers in the field went about finding vulnerability genes for autism,” Fernandez says. “So, we’re using a very similar playbook for childhood anxiety.” “I saw firsthand how researchers in the field went about finding vulnerability genes for autism. So, we’re using a very similar playbook for childhood anxiety.” Thomas Fernandez, MD Associate Professor In the Child Study Center and in Psychiatry Now, Fernandez and Emily Olfson, MD, PhD, assistant professor in the Child Study Center, are studying children and their parents to identify genetic changes that are present in the child but not the parents, known as “de novo mutations.” “All of us have some de novo mutations—maybe about 50 to 100 sprinkled throughout the genome,” Olfson says. “But when they occur within the coding regions of genes, they can be really disruptive.” Previous research shows that people with autism have higher rates of damaging de novo mutations than the general population. In 2022, Olfson, Lebowitz, Silverman, and Fernandez published a study on 68 children and their families that found that children with anxiety had similarly high levels of these mutations. Studying de novo mutations can help point the researchers to where they should be looking for genes associated with anxiety. “The end game is using the genes to steer us toward the right part of biology that we can then target to come up with better treatments,” Fernandez says. Building on those findings, the team is now studying more families to better understand how these de novo mutations, along with other genetic and environmental factors, shape pediatric anxiety disorders. They recently received a National Institutes of Health grant to enroll 750 new families over the next five years. Olfson is the principal investigator, with co-investigators Lebowitz, Fernandez, Silverman, and Shuangge Steven Ma, PhD, department chair and professor of biostatistics at Yale School of Public Health. Neurodevelopment, Risk Genes, and Mental Health Conditions - The Olfson Lab Joel Gelernter, MD, Foundations Fund Professor of Psychiatry, is interested in how different anxiety disorders differ genomically. “We are studying social phobia, panic disorder, and generalized anxiety disorder, working to understand why people differ in their risk to these specific anxiety disorders and evaluating various risk factors,” he says. Gelernter was recently involved in one of the largest studies to date of the genomics underlying anxiety disorder. The study included around 122,000 people with anxiety disorders and around 730,000 without. It found that some genetic differences associated with anxiety were linked to signaling that helps reduce overactivity in the nervous system. Many anxiety medications available today work by targeting this process. “It’s nice when the biology that you get out of a large genome-wide study ratifies things that we already know because that can help increase confidence in further findings from the study,” Gelernter says. Uncovering the neurobiology of psychiatric disorders John Krystal, MD, Robert L. McNeil, Jr. Professor of Translational Research and chair of the Department of Psychiatry, is interested in the neurobiology of psychiatric disorders, including post-traumatic stress disorder (PTSD), of which anxiety is a major symptom. In the late 1980s, Krystal’s team discovered that the drug yohimbine activated symptoms in patients with PTSD. “This was the first time we could link a specific biological mechanism to the symptoms of PTSD,” Krystal says. At the time, he adds, this finding was highly controversial. “A lot of people felt that PTSD was a purely psychological syndrome that didn’t have an underlying biology.” Since then, Krystal has dived deep into understanding the neurobiology of PTSD to learn how to better treat it. His team is evaluating the use of ketamine and psychedelics. These would be among the first treatments to be developed specifically for PTSD. They may also be applicable for other disorders including anxiety disorders, Krystal adds. An important gap in PTSD treatment is the absence of biological tests that inform how to best help patients manage their PTSD symptoms. A doctor doesn’t diagnose cancer based on how they feel. Rather, they use tests of the biology of the cancer to determine the best course of treatment. “And we can’t do that in any psychiatric disorder other than Alzheimer’s disease,” Krystal says. “But now we are building a foundation for this approach to the treatment of anxiety disorders for the first time.” Source: Yale School of Medicine
GrayMatters Health Highlights Growing Role of Digital Biomarkers in Advancing Personalized, Objective Psychiatry
/PRNewswire/ -- GrayMatters Health, the pioneers of digital brain biomarkers for mental healthcare, highlight the role biomarkers are playing in expanding...
Tackling the Health Care Interoperability Problem | Targeted Oncology - Immunotherapy, Biomarkers, and Cancer Pathways
Study Findings Conflict with Body of Science Linking Pesticides to Attention Deficits and Autism - Beyond Pesticides Daily News Blog
A recent study finds no connection between levels of urinary biomarkers of organophosphates and autism-related traits, conflicting with a wide body of research.
“Broken heart syndrome” can look just like a heart attack. This test can tell them apart
“Broken heart syndrome” can mimic a heart attack so closely that patients often need invasive testing to tell the difference. Researchers have now developed the BioTAK score, which combines biological sex with blood biomarkers to identify the condition before cardiac catheterization. In a validation study of nearly 1,800 patients, it correctly classified almost 90% of participants.
The Future of Lymphoma Care Is Moving Forward With Science | Targeted Oncology - Immunotherapy, Biomarkers, and Cancer Pathways
Collagen Peptides Support Bone Health for Female Runners
The study found that biomarkers associated with bone formation increased and inflammation decreased with collagen peptide supplements
Efzimfotase alfa demonstrated improvements in bone health in treatment-naïve pediatric patients with hypophosphatasia achieving median difference of 1.67 vs placebo in RGI-C Score at week 25 in MULBERRY Phase III trial
Positive results from the MULBERRY Phase III trial showed that efzimfotase alfa (ALXN1850), an investigational enzyme replacement therapy, demonstrated a statistically significant and clinically meaningful improvement in bone health in children (2 to
Ezekiel Emanuel: My father lived into his 90s. He understood something many successful men miss
The wellness industry wants you obsessing over biomarkers and supplements. One physician's life offers a simpler—and more effective—blueprint for aging.
Major review finds vaping likely causes lung and oral cancer
Researchers have concluded that nicotine vapes are likely to cause lung and oral cancers, based on evidence ranging from human biomarkers to animal and laboratory studies. The findings challenge the idea that vaping is a harmless alternative to smoking and suggest health risks may be emerging much sooner than many expected.
Using AI for medical advice; pelvic floor exercises; the hidden dangers of burning incense; plus other stories with Vanderbilt Health sources
Colin Walsh, MD,Associate Professor of Biomedical Informatics, was on WTVF News Channel 5‘s “Morningline” show in an interview about whether or not it is safe to use AI for medical advice. Time magazine reporter Stacey Colino interviewed Elisabeth Sebesta, MD, Assistant Professor of Urology, for a story about pelvic floor exercises for issues including menopause, erectile dysfunction and urinary incontinence in men. “Each Breath,” published by the American Lung Association, quoted Brian Christman, MD, Adjunct Professor of Medicine, for a story about the hidden dangers of burning incense. William Schaffner, MD, Professor of Preventive Medicine, was quoted by several news outlets about public health issues, including: Healthline (low vaccination rates lead to more cases of measles, whooping cough and other preventable diseases); ABC News (U.S. measles cases surpass 2,000 for second year in a row); and CIDRAP News (high-dose flu shots cut rates of hospitalization in older adults). Sarah Rohde, MD, Associate Professor of Otolaryngology-Head and Neck Surgery, was quoted in a People magazine story on patient Makalii Andrade, a surfer from Kauai Island who suffered a serious neck injury in 2022 and recently underwent surgery at Vanderbilt Health to begin the final phase of his recovery. James Crowe, MD, Director of the Vanderbilt Center for Antibody Therapeutics, for a piece in Nature about antibodies against a strain of Ebola. SFGATE reporter Gillian Mohney interviewed Xue Zhong, PhD, Research Assistant Professor, Division of Genetic Medicine and Clinical Pharmacology, for a story about a study of a blood test looking at Alzheimer’s disease biomarkers. Matthew Franklin Mart, MD, Assistant Professor of Medicine, was quoted in a Healio story about how inflammation and illness severity is linked to less cognitive resilience after a person has been an ICU patient. The “How We Really Feel” podcast host Sula Windgassen, PhD, interviewed Lindsey C. McKernan, PhD, MPH, Associate Professor of Psychiatry & Behavioral Sciences, Physical Medicine & Rehabilitation and Urology, for an episode focusing on pelvic and bladder health. The podcast is also available on YouTube and the podcast website. In addition, podcaster Monica Sanford interviewed cardiologist Mark Glazer, MD, for her podcast “The Monica Sanford Show”; the two-part interview is here and here.
Materials lab in national program to develop wearable eye health system
The Advanced Research Projects Agency for Health, an agency within the U.S. Department of Health and Human Services, has awarded up to $75.8 million to four research teams through its Ocular Laboratory for Analysis of Biomarkers program. Researchers from Penn State will develop biosensors for the Closed-Loop Sensing and Microdosing for Dry Eye and Systemic Disease Management (COSMIC) team led by Lacristat, a California-based ophthalmology company.
Scientists reversed biological age in older adults with a 4-week diet change
A four-week diet change was enough to make some older adults appear biologically younger in a new University of Sydney study. Participants who reduced fat intake or shifted toward more plant-based protein showed improvements in key health biomarkers tied to aging. The strongest results came from a lower-fat, higher-carb diet, while people eating closer to their usual diets saw almost no change.
The 5 key biomarkers that can tell you how well you're aging — the most crucial is the most overlooked
How aggressive breast cancer turns off the immune system
Researchers are launching a new project to crack the mystery of aggressive breast cancer, where predicting disease progression remains a major hurdle. By studying how tumors interact with and suppress the immune system, scientists aim to identify new biomarkers that reveal how the cancer evolves. Using real patient samples, the team hopes to turn earlier discoveries into practical clinical tools. The goal: more precise, personalized treatments that can outsmart even the most dangerous tumors.
Why are people turning to at-home blood testing? Meet SiPhox Health
SiPhox Health makes at‑home blood testing easy with up to 60 biomarkers starting at $99 — no needles, no lab visits, just clear health insights.
Scientists discover hidden gut signals that could detect cancer early
A new study reveals that gut bacteria and metabolites may hold the key to detecting serious digestive diseases earlier and more easily. Using AI, scientists found that biomarkers linked to one condition can often predict others, showing these diseases are more interconnected than previously thought. This cross-disease insight could lead to faster diagnoses without invasive procedures.
NIH awards $15.8 million to University of California for study of Latino brain health
A multisite study led by UC San Diego and UC Davis will examine changes in brain imaging, blood biomarkers and cognition over time in Latino and Hispanic people.
GrayMatters Health Announces Appointment of Five Expert Advisors
/PRNewswire/ -- GrayMatters Health (GMH), the pioneers of digital brain biomarkers for mental healthcare, today announced the addition of five expert advisors....
Your Thymus and Your Healthspan
Our thymus gland plays a central role in the development or our immune system, specifically for supporting T cell development (how these cells got their name, maturation and differentiation in the thymus) and discriminating between self and foreign, non-self antigen proteins with production of dendritic cells. As we age, our thymus gland shrinks—the process known as involution—with progressive change from spongy to fatty tissue, with loss of functionality. But this process, with respect to timeline and extent, markedly varies from one person to the next. And to make things even more complicated, our thymus gland anatomy and precise location in the chest also is highly variable. So the famous Frank Netter diagrams from the 1960s (such as at left below) don’t capture the remarkable heterogeneity that a random set of 12 chest CT scans (below at right). What I consider as 2 landmark papers in Nature this week (here and here) used AI to quantify health of the thymus in 2 large cohorts, and then correlate the metric to a broad array of health outcomes. In this edition of Ground Truths, I’m going to cover three questions: (1) How was thymus health determined by AI?; (2) How is thymus health linked to key clinical outcomes? and (3) Are there ways we can promote a healthy (aka rejuvenate) thymus gland in our later years? Subscribe 1. How was thymus health determined by AI? This was accomplished by extensive work developing and validating an AI pipeline for 2 stages, the first for localization and segmentation of the thymus bed, and the second to quantify a digital marker, termed the thymic health score. There’s a lot to this algorithmic development, so I won’t go into all the details, but just provide a rudimentary outline of what was done. The 1st stage used supervised learning with 2 radiologists reviewing 2,461 chest CT scans. That work trained a 3D U-Net model to automatically identify the thymic bed’s 3D cropped region using center of mass coordinates, which reached 99.8% accuracy. The 2nd stage used a foundation model that was pre-trained with SwAV (which stands for Swapping Assignment between multiple Views), a self-supervised model, that generated a high-dimensional thymus representation of 4,096 features. That compares to the radiology reductionist and subjective scoring of 0 to 3 where 0 means the thymus is fully degenerated and fatty, and 3 is considered dense, intact glandular soft tissue. Notably, the self-supervised learning (SSL) performance was superior to supervised (AUC ~0.75 vs 0.55, respectively) reflecting the shallowness of the 0-3 classifier vs SSL’s holistic, self-taught AI. The thymic health score ranged from 0 to 100, with the highest number indexed to fully preserved thymic health. The algorithmic work extended to explainability with both Shapely value distribution, meaning the model was holistic not relying on any “magic” pixel, and occlusion sensitivity, demonstrating the model’s performance was not affected by ribs, sternum, lung tissue, but rather focused on the thymic bed directly. Below are a few saliency maps from the occlusion sensitivity that indicate the thymic bed focus, not affected by neighboring structures, using the jet color scale. Now the AI was ready for processing ~25,000 CT scans, each over 30 MB files, from the 2 large participant cohorts to provide a thymic health score, it did so in less than 14 hours, which is less than 2 seconds per scan! Share 2. How is thymus health linked to key clinical outcomes? The two cohorts were the National Lung Screening Trial, NLST (N=25,031) and the Framingham Heart Study, FHS (N=2,581) each with baseline demographics and long term follow up of >12 years for health outcomes. From the NSLT, you can see below that increased age and body-mass index were correlated to reduced thymic health. And, overall, men had reduced thymic health scores compared with women. There are a lot of graphs in the paper for outcomes, for both the NLST and FHS cohorts. To simplify the major outcomes, below is a composite Figure with striking reduction of all-cause mortality and for the different causes of death. The results were consistent between the 2 cohorts. For example, the cardiovascular mortality hazard ratio average was 0.57 in NLST and 0.38 in FHS (weighted to be 0.53 for the aggregate). The reduction of mortality also extended to digestive diseases and pulmonary disease (data not shown below). Lung cancer incidence was reduced by 36% for high vs low thymic health (Figure below, with a panel -incidence and b panel-mortality, adjusted for age, sex, BMI, smoking status). Notably, there was a smoker’s paradox: lower incidence and improved survival for lung cancer in smokers who had a high thymus health score. Smoking was associated with lower thymic scores whereas alcohol was not. Higher thymic health was linked to higher HDL cholesterol, lower triglycerides, lower fasting blood glucose, and lower systolic and diastolic blood pressure. Inflammation biomarkers, such as C-reactive protein and interleukin-6, were elevated in the people with lower thymic health scores. In their second paper, the same team looked at the relationship between thymic score and outcomes for 3,476 patients receiving cancer immunotherapy. The non-small cell lung cancer progression-free survival was reduced in patients with low thymic health score. A parallel relationship for survival was seen for other types of cancer including melanoma, breast, and kidney with a 44% lower risk among high thymic scores (Figure). A similar pattern was seen with different immune checkpoint inhibitors. The thymus health score outperformed programmed death ligand-1 (PD-L1)and tumor mutation burden (TMB) assay of the tumor and was an independent prognostic marker of progression-free survival. In this dataset, a direct connect with thymus score and adaptive immune function was noted with a correlation before cancer treatment for both T-cell diversity and thymus T-cell production (a metric known as T cell receptor excision circles). Thymus Removal Study There is a highly relevant citation about thymus function before moving onto ways to rejuvenate it. In 2023, a very important study of thymus removal during cardiothoracic surgery was published, with 1146 patients undergoing thymus removal vs 1146 matched controls (mean age 55 years). The adverse outcomes for thymus removal were striking, with a 2.9 higher risk of all-cause mortality and doubling of cancer incidence, 1.5 fold increase in cancer mortality, and 1.5-fold increase in autoimmune diseases. The immune function showed marked compromise after thymus removal, as reflected by CD4+ and CD8+ T cells (Figure below) Share Ground Truths 3. Are there ways we can promote a healthy (aka rejuvenate) thymus gland in our later years? In recent months we’ve learned a lot about the process of thymus involution and the pathways by which this may be modulated. Thymus involution is primarily due to loss to thymus epithelial cells (TECs) and there are 2 subtypes with different functions: the cortical, responsible for positive selection of T cells, and the medullary, for negative selection. When adipose tissue infiltrates the thymus, thymic adipocytes are pro-inflammatory, knocking out T-cell output. Likewise, systemic inflammation, or “inflammaging,” from smoking, obesity, and chronic stress promote thymic adipocytes. Now, from preclinical studies, we know about key pathways that account for these processes. Historically, back in 2014, FOXN1 was recognized as a single master transcription factor essential for TEC function, with studies in mice with forced FOXN1 upregulation leading to thymus regeneration. That laid the foundation for potential regrowth of quiescent thymus cells. It took awhile to find pathways to accomplish this goal and to even refute its role as the master regulator. The Liver-Thymus Axis Feng Zhang and his team recently showed that injection of an mRNA vaccine to the liver encoding DLL1, IL-7 and FLT3-L in combination, factors known to support thymopoiesis (Figure), successfully enhanced immune function in aged mice. However, the effect was transient. The FGF21 Story Two reports in 2025 addressed the thymus gland’s production of FGF21, a growth factor (fibroblast growth factor 21) and its control of thymus involution. This growth factor is also produced by the liver, but it doesn’t have impact on the thymus in aged rodent models. In contrast, The liver’s hepatocyte growth factor (HGF) has been shown to reverse senescent TEC structural changes. Growth hormone stimulates production of insulin growth factor-1 (IGF-1) in the liver and the thymus. Two small studies in human participants (TRIIM, for Thymus Regeneration, Immunorestoration, and Insulin Mitigation) of 6 and 50 people, respectively, treated with combined human growth hormone, metformin and DHEA, suggested the potential of slowing epigenetic aging and improving thymus mass and function. But the combination of drugs, small sample, and lack of controls make conclusions murky. Increased thymus FGF21 led to increased CD8 T cells in old mice and extended healthspan and improved physical performance. Building on the previous FOXN1 data, ablation of β-klotho, the obligatory co-receptor for FOXN1, accelerated thymic aging. The benefit to FGF21 was confirmed in a companion paper using an FGF21 knock-in mouse model showing thymus enlargement and increased TECs throughout the lifespan. (schematic Figure below). The accompanying editorial for these 2 papers speculated: “The proposed link between age-associated thymus involution and organismal aging is intriguing, and suggests we might seek to achieve systemic rejuvenation by counteracting thymic involution.” Other Factors Lessons from the Axolotl (Mexican Salamander) In an elegant set of experiments of the axolotl (Figure), known for its complete thymus regeneration after total surgical removal, mediators were identified. Surprisingly FOXN1 was dispensable. But midkine, a growth factor, appeared to be the driver, the initiator of thymus cell growth, survival, and repair. Other components that contributed were Postn+ (periostin-expressing mesenchymal niches) and Ccl19, a chemokine protein from the bloodstream. RANK and RANKL RANK (receptor activator of nuclear factor κB its ligand (RANKL) have been considered key regulators of medullary TECs. In a study of both aged mice and human thymus cell cultures, their key role was confirmed, with multiple benefits of resorting TEC function, recruitment of progenitor cells, and T cell development. Subscribe Summing Up This body of work strongly supports the health of the thymus gland as a critical regulator of human healthspan, not just a correlate or link. The new landmark studies are reinforced by the regenerative biology experimental models that have shown, via an array of mediators, that healthspan of aged mice is at least in part dependent on thymus gland function and its critical role for maintaining adaptive immunity. It sure seems that we’d be better off having an immune reservoir of naive T cells instead of a profile in older adults of exhausted, low quality, memory T cells, with a senescent phenotype. It is striking that we ignored the importance of the thymus gland for many decades. A wake-up call was the results of the thymectomy matched control study reviewed here, with the opposite of high thymic health score improved health outcomes. The convergence of AI and healthspan here is notable. The exceptional and laborious work for developing and validating (no less explaining) the AI to quantify thymus health set the foundation for probing the connect the major health outcomes in two cohorts with extensive follow-up. We’ve never had a way to meaningfully quantify the thymus gland before, so this represents important leverage of supervised, self-supervised, and transformer models. The study wouldn’t have been possible without AI. And it begs the question as to whether there are ways we can maintain our thymus at a high health score. But it’s not so simple to rejuvenate our thymus. There are multiple risks including the induction of autoimmunity, increasing the risk of cancer, and inducing a pro-inflammatory state. For example, factors that increase TEC proliferation could compromise the medulllary negative selection process and leak out auto-reactive (self-attacking) T cells. Thymic cells could be induced to proliferate, but we know, for example, that growth hormone and IGF-1 are associated with an increase risk of cancer. If thymus rejuvenation doesn’t clear out the accumulated senescent cells in older adults, then inflammation within the gland could block the production of TECs. Keeping these risks in mind, we now have identified many ways to keep our thymus healthy as we age that undoubtedly will be tested in clinical trials going forward. Ultimately, the benefit-to-risk tradeoffs will be defined. In the meantime, we have desperately needed an immunome. As I’ve stressed in multiple prior Ground Truths, we have no test in the clinic to assess a patient’s immune status! It was very encouraging for me to get an email from Hugo Aerts, the senior author of the landmark papers in the days after they were published: “I also wanted to say that your Substack on “Why We Need an Immunome” was inspiring for this work. We found it a very compelling perspective and greatly enjoyed reading it.” Just having an assessment of a person’s immune status via a chest CT scan, with millions of these performed per year, might help in guiding the right immunotherapy for cancer (e.g. more intensive, combinations for those with low thymic health scores) and help define people who are increased risk for age-related diseases of cancer, cardiovascular, and neurodegenerative. The main theme of Super Agers is that we now have many layers of data (genetics, proteins, biomarkers, organ clocks that can be integrated via multimodal AI) for us to define a person’s specific risk decades before one of these age-related diseases leads to symptoms, enabling prevention. From the new studies this week, we can add thymus health score as yet another way to understand a person’s risk, a window into their adaptive immune system and healthspan. And perhaps someday we will be able to safely rejuvenate the thymus, or maintain its health through one’s life, and use the thymus health score to monitor. NB: I wrote this post (No A.I.) A Quick Poll Loading... ********************************************************************* Thanks to Ground Truths subscribers (now > 200,000) from every US state and 212 countries. Your subscription to these free essays and podcasts makes my work in putting them together worthwhile. Please join! If you found this interesting PLEASE share it! Share Ground Truths Paid subscriptions are voluntary and all proceeds from them go to support Scripps Research. They do allow for posting comments and questions, which I do my best to respond to. Please don’t hesitate to post comments and give me feedback. Let me know topics that you would like to see covered. Leave a comment Many thanks to those who have contributed—they have greatly helped fund our summer internship programs for the past two years. It enabled us to accept and support 47 summer interns in 2025! We aim to accept even more of the several thousand who will apply for summer 2026.
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