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Scientists spur growth of implanted liver tissue
Researchers developed a way to control the growth of lab-grown liver tissue after it was implanted into mice.
New MatterChat Model Helps AI to ‘See’ the Language of Science
From writing emails to generating computer code, much of the artificial intelligence prevalent in our daily lives has succeeded by mastering one domain: text. However, this leaves a major blind spot in the physical sciences, where models depend on the high-resolution, three-dimensional data of the physical world, like the intricate lattice of atoms in a crystal. Delivering on the promise of using AI for science requires teaching these data-driven text models to seamlessly “talk to” physics-based models. Now, a new AI framework from Lawrence Berkeley National Laboratory (Berkeley Lab), called MatterChat, solves this problem by creating a specialized “bridge.” It connects the conversational power of a Large Language Model (LLM) with a physics-based AI that models “interatomic potentials”: the complex physical forces between atoms. The resulting system already significantly outperforms general-purpose AI tools like GPT-4 at predicting material properties, and the team hopes it can accelerate scientific discovery by serving as a robust research partner that provides grounded insights and generates step-by-step instructions for synthesizing novel materials. A paper describing this work was recently published in Nature Machine Intelligence. “Traditional simulations can provide the physical rigor required for materials science, yet their computational cost remains prohibitive for high-throughput screening. Conversely, while LLMs excel at rapid knowledge synthesis, they inherently lack the ‘structural vision’ to interpret materials directly from their underlying atomic coordinates,” said Yingheng Tang, a postdoctoral researcher in Berkeley Lab’s Applied Math and Computational Research Division (AMCR) and lead author on the paper. “MatterChat was built to solve this dilemma, empowering LLMs with a structural ‘vision’ that allows researchers to leverage their full potential for solving complex, real-world materials challenges.” Empowering language models to solve complex challenges in materials science To build MatterChat, the Berkeley Lab team drew inspiration from technologies like Vision Question Answering (VQA) and Text-to-Image (T2I) generation. In these tasks, AI must translate high-level text concepts into visual images, or vice versa. Doing so requires developers to build tools that “bridge” two fundamentally different forms of data. The researchers adapted this concept to the physical sciences. With MatterChat, they created a “bridge model” that successfully connects an LLM’s general knowledge with the deep understanding of the atomic-scale world encoded in scientific interatomic potentials. Until now, researchers using LLMs to solve materials problems usually had to feed them raw data files as if they were just strings of text. It’s like asking an AI to understand a complex 3D engine based only on a parts list: the LLM can read the names, but it can’t “see” how the atoms fit together in space. MatterChat solves this by training a specialized AI bridge model, pre-trained on millions of crystal structures and an LLM, to align the LLM’s representation of the world with the interatomic potential’s representation of the world. The bridge model can translate physical insights into a format the LLM can actually understand. By giving the LLM these “scientific eyes”— a scientific “inductive bias” in the terminology of AI — the Berkeley Lab team has transformed it into a robust research tool capable of providing grounded scientific insights into complex materials challenges, such as predicting thermal stability or analyzing electronic band gaps. “We think of atoms as living in a physical space, but from a machine learning perspective, they are just vectors living in some very non-trivially structured manifold in a high-dimensional Euclidean space; and, of course, the same is true for the sentences and paragraphs that we use to express our ideas about those atoms,” said co-author Michael Mahoney, Berkeley Lab’s Scientific Data Division (SDD) AI Initiative Research Lead. “The bridge model basically gets those two structures to ‘talk with’ each other.” As a proof-of-concept of this general approach, the team trained their bridge model on a dataset curated by pairing nearly 143,000 stable atomic structures from the Materials Project with their corresponding physical properties. This training data was automatically assembled using the Materials Project’s API and deliberately enriched with properties fundamental to microelectronics design — like formation energy and bandgap — allowing MatterChat to learn the complex patterns connecting a material’s atomic blueprint to its functional performance. To validate their model, the researchers benchmarked MatterChat against a suite of other AI systems, from general-purpose LLMs to other specialized scientific AI methods. The results show that MatterChat consistently outperformed its competitors across a range of tasks. The model was more accurate in classifying material types and demonstrated superior precision in predicting numerical properties. For example, it excelled at predicting a material’s bandgap, a property critical for designing new electronics from high-capacity energy storage to next-generation computer chips. “Our design is significantly more efficient because we don’t have to build a massive AI model from the ground up,” said co-author Zhi (Jackie) Yao, a research scientist in Berkeley Lab’s AMCR. “Instead, we take two powerful, pre-trained models — a structural encoder for materials physics and an open-source LLM — and use them off-the-shelf. The only component we actually train is the lightweight ‘bridge model’ that translates between them. It’s the difference between building an entire car factory and simply designing a smart adapter that connects a world-class engine to a world-class navigation system. This approach is not only computationally efficient, but also makes the system modular, so we can easily upgrade components or adapt the bridge for other scientific domains in the future.” Crucially, this modular design highlights exactly how institutions like Berkeley Lab and the Department of Energy are carving out a highly valuable niche in the booming AI landscape. Rather than competing with Silicon Valley tech giants to build ever-larger language models from scratch, the lab is focusing on the specialized connective tissue that makes commercial AI useful for hardcore science. Because the bridge model approach underlying MatterChat is forward-compatible, it is perfectly positioned to leverage these parallel tracks of innovation. As Mahoney pointed out, “We expect that industry will continue to develop improved LLMs, and we expect domain scientists and facilities will continue to generate new data. An important part of scientific machine learning is not simply to solve problems on today’s data, but instead to develop general methods that will be forward-compatible with orders of magnitude more data, whether from scientific domains or from LLMs.” According to Yao, the MatterChat project, which was initially developed and enhanced with funding from a Berkeley Lab Laboratory Directed Research & Development (LDRD) Program, will now expand its capabilities. In a collaboration with Fermilab, MatterChat is already contributing to a U.S. Department of Energy Genesis Mission project — called Accelerating eXtreme Environment Specs-to-Silicon (AXESS) — that aims to speed up the development of next-generation, high-speed, radiation-hardened detectors for challenging particle physics experiments by using advanced 3D integrated circuits (chiplets) and AI-driven data analysis. In addition to the LDRD support, the team also credits supercomputing resources at the National Energy Research Scientific Computing Center (NERSC), located at Berkeley Lab, with MatterChat’s success. “We are incredibly grateful to NERSC; this research simply would not have happened without access to the Perlmutter supercomputer through their AI for Science program,” said Tang. Wenbin Xu, a NERSC postdoctoral fellow at the time, was also a major co-author of the work, as was Benjamin Erichson, a research scientist in Berkeley Lab’s SDD, highlighting the benefits of AMCR-SDD collaboration on AI for science. ### Lawrence Berkeley National Laboratory (Berkeley Lab) is committed to groundbreaking research focused on discovery science and solutions for abundant and reliable energy supplies. The lab’s expertise spans materials, chemistry, physics, biology, earth and environmental science, mathematics, and computing. Researchers from around the world rely on the lab’s world-class scientific facilities for their own pioneering research. Founded in 1931 on the belief that the biggest problems are best addressed by teams, Berkeley Lab and its scientists have been recognized with 17 Nobel Prizes. Berkeley Lab is a multiprogram national laboratory managed by the University of California for the U.S. Department of Energy’s Office of Science. DOE’s Office of Science is the single largest supporter of basic research in the physical sciences in the United States, and is working to address some of the most pressing challenges of our time. For more information, please visit energy.gov/science.
What’s Next for Artemis II AVATARs
Organ chips from Artemis II's AVATAR investigation have arrived at the laboratory at Emulate, Inc. in Boston, Massachusetts for analysis. The AVATAR (A Virtual Astronaut Tissue Analog Response) investigation uses personalized organ chips made from each astronaut's own cells to study the impacts of space radiation and microgravity on human health.
A grad student’s wild idea sparks a major aging breakthrough
A casual conversation between graduate students helped spark a breakthrough in aging research at Mayo Clinic. Researchers discovered that tiny synthetic DNA molecules called aptamers can selectively attach to senescent “zombie cells,” which are linked to aging, cancer, and neurodegenerative disease. The method could eventually help scientists identify and target these cells in living tissue with far greater precision.
Time matters: circadian genetics and the molecular logic of human health and disease
Nature Reviews Genetics - The circadian clock controls transcriptional and signalling networks across tissues to maintain homeostasis, with pathological consequences to its disruption. Kuo et al....
Apreo Health® Adds Independent Director and Strategic Investor to Advance Novel Airway Scaffold for Severe Emphysema
Apreo Health, a clinical-stage medical device company pioneering a tissue-sparing treatment for severe emphysema, today announced the appointment of David Amerson to its Board of Directors and a strategic investment from OSF Ventures, the corporate investment arm of OSF HealthCare. The company also announced it will present new clinical data at the American Thoracic Society (ATS) 2026 International Conference in Orlando, Florida.
Scientists discover hidden fat-burning switch that could strengthen bones
Scientists at McGill University have uncovered a hidden molecular “switch” that turns on a powerful calorie-burning system in brown fat — the body’s heat-generating fat linked to metabolism and weight control. The breakthrough centers on glycerol, a molecule released when fat is broken down in the cold, which activates an enzyme called TNAP and triggers an alternative heat-producing pathway that scientists had struggled to explain for years.
Black licorice compound shows promise against inflammatory bowel disease
Researchers have developed a stem cell-based model of the human intestine that may transform how new IBD treatments are discovered. After testing thousands of compounds, they identified glycyrrhizin — a natural substance found in black licorice — as a promising anti-inflammatory candidate. In both lab-grown tissue and mice, the compound reduced intestinal damage and cell death linked to IBD.
Scientists found the “holy grail” gene that could one day help humans regrow limbs
Scientists studying axolotls, zebrafish, and mice have uncovered a shared set of genes that may one day help humans regrow lost limbs. By identifying powerful “SP genes” involved in regeneration, researchers discovered that disabling these genes stopped proper bone regrowth in salamanders and mice. They then used a gene therapy inspired by zebrafish biology to partially restore regeneration in mice, marking a major step toward future treatments that could replace damaged limbs with living tissue instead of prosthetics.
New obesity discovery rewrites decades of fat science
Scientists have uncovered a surprising secret hidden inside fat cells that could reshape how we think about obesity and metabolic disease. A protein called HSL, long believed to simply release stored fat when the body needs energy, turns out to have a second job deep inside the nucleus of fat cells—helping keep those cells healthy and balanced. Even more surprising, people and mice missing this protein don’t become obese as expected; instead, they lose fat tissue in a dangerous condition called lipodystrophy.
Resilia tissue developed by Edwards Lifesciences associated with long-term durability
Kevin Accola, MD, spoke to Cardiovascular Business about new 10-year data on the performance of surgical valves featuring Resilia tissue. The findings are good news for Edwards Lifesciences, which also includes the tissue on many of its TAVR devices.
4D mammo may be up to four times more accurate than 3D
The 4D system harnesses X-ray diffraction to measure molecular-level signatures of disease; these tissue “fingerprints” could help providers diagnose breast cancer in its earliest stages.
Surprising obesity discovery rewrites decades of fat metabolism science
A key protein involved in fat metabolism has been found to do more than scientists once thought. Instead of just releasing fat, it helps maintain healthy fat tissue and balance in the body. When it’s missing or disrupted, the results can be surprisingly harmful. This finding reshapes how researchers think about obesity and metabolic disease.
Viewpoint: A career in science is possible, and worth it
Starting a career in science is exciting, but also demanding, with researchers often faced with intense competition, long working hours and high levels of stress. A pioneer in the field of mass spectrometry, Carol Robinson has been there. She speaks with Science|Business on the importance of creating a supportive environment, particularly for women.Robinson did not wake up one day thinking that she would become a scientist. It was only late in school that she developed an interest in chemistry. “The more you work at something, the more you think, actually, this is fascinating. So, I went much further and deeper than I ever needed to pass the exam. And then I loved it,” she says. “I thought, I’m going to give it my all. I’m going to enjoy it while I’m here. But I didn’t think this would be my career for 50 odd years.”She left school at 16 to become a lab technician with the drug company Pfizer, which is where she first worked with mass spectrometry. Fascinated, she was encouraged to take a part-time degree and then a PhD. She went on to do pioneering work in native mass spectrometry, a technique that is used to study protein structures in their natural state, paving the way for breakthroughs in drug discovery. She also broke new ground by becoming the first female professor of chemistry at the University of Cambridge, and then the first female professor of chemistry at the University of Oxford, her current home.She now wants to show young researchers that a career in science is worth it. “Sometimes, I believe the culture isn’t very encouraging, and that’s something I have worked on,” Robinson says.In 2021, she launched the Kavli Institute for Nanoscience Discovery at Oxford, whose acronym gives a sense of what she hopes it will achieve. “Maybe it is corny,” she says. “It’s just a reminder that I would like it if we could all be kind to each other and supportive, especially for early-career researchers of either gender, because there’s quite a big attrition rate in science, and maybe it just doesn’t feel like a very friendly place to work.”And yet, a career in science comes with a lot of flexibility. “There are few careers where you have that amount of freedom, to go to conferences, to the library. Just because you didn’t see me didn’t mean I wasn’t working,” she says. “And I’m excited to come in every day. So, I don’t want people to think it’s a terrible place.”Gender equality is also important when it comes to the quality of science as a career. “The more women we have, the better it becomes,” Robinson adds.Imposter syndromeAccording to EU data, women outnumber men in university education but account for just about a third of graduates in science, technology, engineering and mathematics (Stem). And while the number of women working as scientists and engineers in the 27-member bloc is on the rise, their representation remains below that of men, at 41%. This discrepancy is even more pronounced in top-tier functions across these fields, where women fill just 20% of positions.Having supervised many young scientists, Robinson sees that women continue to have a greater propensity than men to doubt their abilities, a feeling she once shared. “When I was doing my PhD at the University at Cambridge, I really felt like an imposter,” she says. “I don’t think I ever felt I deserved to be there or owned it and was proud. I just thought I was lucky.” Later on, she adds, “I was always that person who said, I can’t apply yet because my CV is not strong enough.”She has now made it her job to encourage women to break with this imposter syndrome. For example, rather than calling for volunteers to give a lecture in the groups that she mentors or teaches, which nearly always results in men stepping forward, she goes straight to the women, “because I know they won’t push themselves forward.”But the gender gap in science is not just down to imposter syndrome. The “obvious” reason, Robinson says, and the reason that is on everybody’s mind when discussing workplace gender equality, is the balance between work and raising a family. Her own path was to choose between the two, taking an eight-year break after completing a postdoctoral training fellowship to bring up three children. And she continues to advise women not to work part-time while they raise a family. “You’ll just get half the pay and continue to work full-time because you are not able to fit everything in,” she says. “You should be able to have a family and come back to have the career that you want.”The solution is for men to also take career breaks. “That kind of evens it up, so that it’s not such a big thing for women,” Robinson says. “I always encourage men in my groups to do that. I think it’s important to take your share of the duties.”Support produces resultsAccording to the Women in Stem Network, a UK advocacy group, countries with strong childcare systems and equal pay policies retain more women in technical careers. In Europe, these are primarily found in the Nordic region and parts of central Europe.At the EU level, the European Commission asks all Horizon Europe applicant organisations to have a gender action plan in place. Since this criterion was introduced in 2021, the share of women leading consortia has increased to 31%, against 23% in Horizon 2020. Their overall participation, however, has risen just 1%, to 38%. After trying to weaken the requirement for gender action plans in 2025, the Commission now intends to adopt a plan for supporting women in research and innovation.Related articlesCommission scraps plan to water down gender requirements in HorizonHow gender balance can swing who wins Horizon Europe fundingRobinson herself has benefited from three Advanced Grants from the European Research Council. “I was extremely honoured and privileged to get those, because they really allowed me to fuel my passion,” she says. “Without that, it would have been a much harder slog.”Beyond applying gender rules, she says that more work is needed on translational enterprise, where women are, once again, largely underrepresented. The European Patent Office found that only 13.8% of applications were filed by women in 2022. “We have so many more women doing amazing science; why do they feel it’s not a thing to have a company?” she asks.She founded her own spin-out company, OMass Technologies, in 2016, and remains chair of its scientific advisory board now that it trades as OMass Therapeutics. As for research, Robinson is now studying how changes in the brain may be linked to depression, using port-mortem tissue. “We’re hoping to publish soon,” she says. “We had to consult with a lot of people who knew a lot more about the brain than we did. So, we’ve learnt a lot, and that’s always a lot of fun to learn a new thing. That’s what keeps you going.”
Can Collagen Supplements Really Improve Skin and Joint Health? Here's What a Pharmacist Says
Taking collagen supplements can help improve skin and joint health, as it's an important component of skin, and bone tissue.
Scientists discover how to freeze transplant organs without cracking them
Scientists are making a major leap toward freezing organs for future use without damaging them. A new study reveals that one of the biggest obstacles—cracking during ultra-cold preservation—can be reduced by carefully tuning the temperature at which tissues enter a glass-like state. This breakthrough builds on recent successes in cryopreserved organ transplants and could bring the long-imagined idea of “banking” organs for later use much closer to reality.
Scientists finally solve mystery of strange “golden orb” found 2 miles deep
A mysterious “golden orb” found more than two miles deep in the Gulf of Alaska left scientists baffled for over two years, sparking wild speculation about its origins. After an intensive investigation combining deep-sea expertise, microscopic analysis, and advanced DNA sequencing, researchers finally cracked the case. The strange object turned out not to be an egg, sponge, or anything alien, but the remains of tissue from a giant deep-sea anemone.
You Can Actually Regrow Your Fingertips. Scientists Just Figured Out How.
You can regrow damaged skin in the area, sure—but also bone, tissue, and nerves.
What if humans could regrow tissue? New study moves science closer
For centuries, the inability to regrow lost body parts has been considered a defining limitation of humans and other mammals. While animals like salamanders can regenerate entire limbs, humans are left ...
What if humans could regrow tissue? Texas A&M study moves science closer
Researchers have successfully regenerated skeletal and connective tissue — even if not perfectly formed — demonstrating the next, critical step in limb regeneration.
Thursday Morning Links
Morning, all! Wyatt Langford has a grade 1 flexor strain in his right arm, which marks the fifth IL stint for a soft tissue injury in the first two years of his career. Skip Schumaker says it’s because he “has more muscles than most people.” Langford is hoping to spend no more than the minimum […]
For the first time, scientists pinpoint the brain cells behind depression
Scientists have identified two specific types of brain cells that behave differently in people with depression, offering a clearer picture of what is happening inside the brain. By analyzing donated brain tissue with advanced genetic tools, the researchers found changes in neurons linked to mood and stress, as well as in immune-related microglia cells. These differences point to disruptions in key brain systems and reinforce that depression is rooted in biology, not just emotions.
Offworld Life Science: Research Hardware For A Biotechnology Investigation
configures research hardware inside a portable glovebag for a biotechnology investigation exploring how bacteria affect heart tissue in the microgravity environment.
How can scientists visualize cellular life with greater precision? - Salk Institute for Biological Studies
Highlights Salk researchers collaborated with scientists at Albert Einstein College of Medicine to develop a new class of probes for imaging living cells The probes, called visible-spectrum antigen-stabilizable fluorescent nanobodies (VIS-Fbs), generate high-contrast images with minimal disruption to normal cellular activity The technology enables more precise investigation of complex biological processes, including cell signaling, development, and disease progression LA JOLLA—Fluorescent proteins have revolutionized science, enabling researchers to tag and visualize individual molecules in living cells, tissues, and animals. Using these tools, researchers have watched viruses infect cells in real time, observed cellular trash collection, and tracked the signaling that spurs tumor growth.
Mechanohealth: Where life science meets physical forces for health innovation
Integrating mechanobiological principles into disease pathogenesis, therapeutic development, and tissue engineering is reshaping our understanding of biological systems and accelerating the advancement of mechanotherapy and mechanohealth. This field reveals how mechanical cues regulate cellular behavior, such as force transmission along integrin-nucleus pathways and collective cell migration, and tissue functions. In doing so, mechanobiology connects fundamental research with clinical applications, from limiting cancer metastasis and fibrosis to promoting bone regeneration and maintaining vascular homeostasis. Building on discussion from the Inaugural International Conference on Mechanobiology (ICM) 2025, integrating mechanobiological research with clinical strategies offers new opportunities to address unmet needs, including personalized anti-fibrotic interventions or precision bone regenerative therapies. At the same time, it supports the broader concept of mechanohealth -- a paradigm focused on preserving the physiological mechanical balance within tissues.
Scientists remove “zombie” cells and reverse liver damage in mice
A rogue set of “zombie” immune cells may be driving aging and fatty liver disease by flooding tissues with inflammation. Researchers found these cells accumulate with age and high cholesterol—and can make up most of the liver’s immune cells in older mice. When scientists removed them, liver damage was dramatically reversed, even without diet changes.
Atelerix Forms Strategic Partnership With JH Health Ltd to Expand Non-Cryogenic Cell Preservation Capabilities in the Middle East
NEWCASTLE, England, April 15, 2026--Atelerix, a biotech company revolutionising cell preservation and biological transport with its pioneering hydrogel encapsulation technology, today announced it has established a strategic partnership with JH Health Ltd, a Saudi Arabian company focused on medical and health-related technology. The partnership grants JH Health exclusive rights to use and distribute Atelerix’s hydrogel-based cell and tissue preservation solutions in the Middle East, significantl
Diabetes rates are lower in high-altitude environments — and scientists may have discovered why
A new study finds that in low-oxygen environments, red blood cells absorb more glucose and convert it into a molecule that helps release oxygen into tissues, revealing an unexpected way the body regulates blood sugar.
Diabetes rates are lower in high-altitude environments — and scientists may have discovered why
A new study finds that in low-oxygen environments, red blood cells absorb more glucose and convert it into a molecule that helps release oxygen into tissues, revealing an unexpected way the body regulates blood sugar.
Scientists Discover Why Flu and COVID Hit Older Adults So Hard
A new study reveals that aging lungs may play a major role in why flu and COVID can become so dangerous for older adults. Researchers found that certain lung cells can trigger an exaggerated immune response, creating clusters of inflammatory cells that end up damaging lung tissue instead of protecting it. In experiments, activating this aging-related signal in young mice caused their lungs to behave like older ones, leading to severe illness.
Surprising study shows Alzheimer's may start in the body instead of the brain, a discovery that turns medical science upside down
Alzheimer’s disease may begin outside the brain, with inflammation in organs like the skin, lungs, and gut decades before symptoms appear.
Researcher Shows Anxiety Could Be Linked to a Nutritional Deficiency
Research shows that people with anxiety disorders had significantly lower choline levels in their brain tissue.
Scientists discover a hidden system that turns brown fat into a calorie burner
Scientists have identified a key biological system that helps brown fat burn energy by building the networks it needs to function. A protein called SLIT3 splits into two parts, with each piece guiding the growth of blood vessels and nerves inside brown fat. These structures allow the tissue to pull in nutrients and rapidly convert them into heat instead of storing them as fat.
Understanding protein motion could greatly aid new drug design
For many of us, “protein” is the key element of a food order. However, beyond your preferred choice of meats or plant-based alternatives, proteins encompass a large class of complex biomolecules whose chemical structure is encoded in our genes. Proteins have critical functions in living cells: They help repair and build body tissues, drive metabolic reactions, maintain pH and fluid balance, and keep our immune systems strong.
UM Health-Sparrow honored for organ, tissue donation impact
University of Michigan Health-Sparrow will receive an award Wednesday for its efforts in giving patients a second chance at life through organ and tissue donation.
Episode 68, Science for Success, Tissue testing and Potassium
By Dusty Sonnenberg, CCA, Field Leader, a project of the Ohio Soybean Council and Soybean Check-off In Episode 68, Dusty visits with soybean researchers involved in the Science for Success program. Science for Success provides timely, cutting-edge best management practices by coordinating the uni
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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