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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.
Today’s Papers – Italy’s World Cup mission, Napoli’s comeback
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Frank Vizetelly’s illustration titled “Night Amusements in the Confederate Camp” appeared in the Illustrated London News on January 10, 1863. It was one among a number of wartime scenes that Vizetelly captured for the newspaper. Subscribe Following the war, the illustration appeared in a number of books, including John O. Casler’s Four Years in the Stonewall Brigade (1893) and Campfires of the Confederacy (1898) by Ben La Bree. The scene depicts a Confederate camp at night with an enslaved man, most likely a camp servant, performing a dance around a fire with the music provided by a soldier playing a banjo. Another enslaved man looks on at the right. Vizetelly likely witnessed the scene—one that would have been common throughout the war. It’s a wonderful example of the way in which Confederates—slaveowners and nonslaveowners alike—experienced the presence of slave labor in the army. Vizetelly was deeply sympathetic to the Confederate cause. His depiction of the enslaved man as more than happy to entertain the very people who were fighting to keep him enslaved was precisely the kind of image designed to reassure a British audience that slavery was benign, and by implication, that Britain need not feel morally troubled about recognizing or supporting the Confederacy. Share Just as importantly, the sight of a dancing slave reassured Confederates themselves that the institution of slavery remained secure even after President Lincoln signed the Emancipation Proclamation. I’ve come across this illustration many times before and I plan on using it in my next book project on the role of enslaved labor in the Confederate army during the Gettysburg Campaign, but this is not the reason I am sharing it with you today. It has to do with where I recently found it, which came as a complete surprise and is incredibly revealing. Let’s take a look.
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Daniel Miller
Daniel Miller is a reporter at POLITICO covering the intersection of entertainment, media, sports, technology and politics.Part of POLITICO’s California team since 2026, he examines how Hollywood and Southern California function as engines of political power. Daniel also covers the rainmakers, dealmakers and cultural figures who shape policy debates, elections and public life far beyond the state’s borders.Daniel previously spent 13 years at the Los Angeles Times, most recently as an enterprise reporter in the newspaper’s Metro department, where he worked on investigations and features. He wrote about allegations of sexual misconduct at L.A.’s Magic Castle, chronicled the cratering ventures of a celebrity vegan chef and detailed themystery of a missing million-dollar pocket watch once owned by J.P. Morgan. In 2019, he wrote, reported and hosted "Larger Than Life," an award-winning podcast about the life of an enigmatic L.A. street racer.He previously covered the business of entertainment for The Times, examining the fraught political ties between the Walt Disney Co. and the city of Anaheim, probing the world of second-tier talent agents operating on Hollywood’s fringes and uncovering allegations involving several #MeToo figures.Daniel was named Journalist of the Year at the 2015 National Arts & Entertainment Journalism Awards and, a year later, received the L.A. Press Club’s Entertainment Journalist of the Year award. He was also a finalist for the 2016 Loeb Awards for "Selling Stardom," a series on unscrupulous Hollywood operators. His narrative reporting has been honored by organizations including the Society for Features Journalism, the National Association of Black Journalists and the Motor Press Guild.Daniel began his career reporting in Southern California, writing for the Ventura County Star, the Los Angeles Business Journal and the Hollywood Reporter. He attended Beverly Hills High School and UCLA. He lives in Los Angeles.
DAV announces new partnership with Solace Health supporting veterans’ care
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Behind a collection of gravestones, Fred “Corky” Donatelli III arranges papers at his desk. His hands are big and rough, dusted with dirt...
Some Florida voters foresee voter access changes if SAVE America Act becomes law
The act would require voters to bring photo ID and proof of citizenship, such as passports, an original birth certificate or naturalization papers.
Danbury OKs ‘ugly on paper’ zone change to benefit local business
"To be very frank, the petition looks ugly on paper, because we just got finished getting rid of these things,” said Theodore Haddad.
A Tragedy of Early COVID Has Finally Been Explained
Dangerous blood clotting associated with certain vaccines had a genetic cause, according to a new paper.
NASA's Viking Mission May Have Found Alien Life In 1976 And Accidentally Killed It
A new paper suggests that BARSOOM may have been alive on the planet, and was killed in the Viking experiments.
Scientists See Growing Risk of 'Hothouse Earth' as Warming Gains Pace
Warming is accelerating, threatening a cascade of tipping points that destabilize the climate. In a new paper, scientists say the risk of "hothouse Earth" is greater than once believed.
Why Jeff Bezos gutted the Washington Post
Hundreds of jobs have gone at the newspaper that broke the Watergate scandal. Was profit or politics behind the decision? Jeremy Barr reports
Sports leagues race to capture Gen Z and Gen Alpha with AI, influencers and Italian brainrot
CHICAGO (AP) — Trevor McOmber and his 14-year-old son, Tye, share a love for the Chicago Blackhawks. When Trevor was his son's age, he watched the Blackhawks on TV, caught highlights on ESPN and read about the team in the newspaper.
Capital One Seizes Control of Discovery Behavioral Health After Defaulting on Debt
Capital One has taken over Webster Equity Partners’ portfolio company, Discovery Behavioral Health. Court documents show that Capital One and its
An Olympian Made One Small Comment About the State of the Country, and MAGA Lost Its Mind
The president and his sycophants really do have paper-thin skin.
Jon Kudelka, much-loved Australian political cartoonist, dies aged 53
Award-winning Tasmanian artist’s work was published by The Australian, The Saturday Paper and The Hobart Mercury
Washington Post owner Jeff Bezos gives first statement after layoffs
Washington Post owner Jeff Bezos has put out his first statement since the paper's cuts. He said "data tells us what is valuable and where to focus."
Washington Post union calls for Jeff Bezos to sell the paper
In a statement released Saturday following the ouster of Washington Post CEO Will Lewis, the Post's union called for Jeff Bezos to sell the paper.
Washington Post CEO out days after sweeping layoffs
Will Lewis, the CEO of The Washington Post, announced his departure from the beleaguered paper on Saturday afternoon.
After Almost a Century, Readers Close Mass Market Paperbacks
E-books and pricier formats push cheap pocket novels toward extinction
Saying Goodbye to the Mass Market Paperback
The mass market paperback, light in the hand and on the wallet, once filled airport bookstores and supermarket media aisles. You may never buy a new one again.
Nationals praise Washington Post sports reporters
The Washington Nationals gave a shoutout to Washington Post reporters, a day after the newspaper announced plans to shut down its sports department as part of company-wide cuts. “Journalists from T…
House Republicans sound alarm over CCP-linked fake research threatening US taxpayer-funded science
House Republicans warn Chinese "paper mills" may be flooding U.S. science with fake research, potentially compromising taxpayer-funded programs and grants.
This paper-thin chip turns invisible light into a steerable beam
Researchers have built a paper-thin chip that converts infrared light into visible light and directs it precisely, all without mechanical motion. The design overcomes a long-standing efficiency-versus-control problem in light-shaping materials. This opens the door to tiny, highly efficient light sources integrated directly onto chips.
‘Deep and profound sadness’: Washington Post sports reporter shares emotions after mass layoffs at the paper
Jesse Dougherty was among those who lost their job Wednesday as part of the mass layoffs that gutted the staff of the D.C.-area’s hometown newspaper The Washington Post. He shared the emotions upon hearing the news with WTOP’s Nick Iannnelli.
It’s Time to Pay Our Last Respects to The Washington Post
Democracy, the Post says, dies in darkness. Nowadays, newspapers are murdered in broad daylight.
The Murder of The Washington Post
Today’s layoffs are the latest attempt to kill what makes the paper special.
MIT's new brain tool could finally explain consciousness
Scientists still don’t know how the brain turns physical activity into thoughts, feelings, and awareness—but a powerful new tool may help crack the mystery. Researchers at MIT are exploring transcranial focused ultrasound, a noninvasive technology that can precisely stimulate deep regions of the brain that were previously off-limits. In a new “roadmap” paper, they explain how this method could finally let scientists test cause-and-effect in consciousness research, not just observe correlations.
OVC Celebrates National Girls and Women in Sports Day
February 4th marks the 40th Annual National Girls & Women in Sports Day™ (NGWSD).
'Win within Edinburgh's grasp but for poor kicking'
Edinburgh have played four games in the past two seasons that have been officiated by Andrea Piardi and have lost all of them. On paper, we should have had a chance against Leinster but by now we all know that the paper lies. A few decisions felt like they went against Edinburgh, least of all the chalked-off try on the 25 minute mark.
Baladins Is An Adorable Tabletop-Inspired Co-Op RPG With A Papercraft Aesthetic
Coming to Switch later this month
ICYMI: Paper Mario-Styled RPG 'Escape From Ever After' Has Launched On Switch
And it's riding high on Metacritic
‘Ending the HIV Epidemic’ Health Fair set for Feb. 11
The Office of Community Advocacy and the Florida Department of Health (DOH) in Miami-Dade County will join various community providers to co-host the annual “Ending the HIV Epidemic” Health Fair....
Scientists discover hidden geometry that bends electrons like gravity
Researchers have discovered a hidden quantum geometry inside materials that subtly steers electrons, echoing how gravity warps light in space. Once thought to exist only on paper, this effect has now been observed experimentally in a popular quantum material. The finding reveals a new way to understand and control how materials conduct electricity and interact with light. It could help power future ultra-fast electronics and quantum technologies.
Health Department releases food inspection reports for week of Jan. 18
Find out how your favorite restaurant, convenience store and other food establishments in Jefferson County are performing on Health Department inspections.
The Detroit News now part of USA TODAY Network
The Detroit News is officially part of USA TODAY Co.’s network of more than 200 newspapers.
Dr. Michael Greger’s Bias Is Food for Thought
How can we distinguish between a sufficiently objective science communicator and an advocate? Communicating science to the public means choosing scientific papers, reading them, and appraising their
Make an Honest Living in Three New GTA Online Odd Jobs
Join the ranks of the Los Santos Fire Department as a Firefighter, load up delivery vans for Alpha Mail as a Forklift Operator, or deliver the old-fashioned printed version of the Los Santos Meteor with a Paper Route in three new Odd Jobs now available...
Are These Unprecedented Times for Science, Really?
A science historian looks to the past to understand our current moment, and how ghostwriting in scientific papers is harming public trust.
Samsung's Cool New Gadget Has The First Display Of Its Kind In The World
The 13-inch Samsung Color E-Paper features the world's first display housing made in part with a bio-resin crafted from phytoplankton, a type of microalgae.
Samsung Debuts 13-Inch Color E-Paper, a World-First Display Built With Bio-Resin Derived From Phytoplankton
Built with UL-verified phytoplankton bio-resin materials, the display delivers ultra-low-power performance with local and remote management via Samsung E-Paper App and Samsung VXT
OpenAI’s latest product let’s you vibe code science
OpenAI just revealed what its new in-house team, OpenAI for Science, has been up to. The firm has released a free LLM-powered tool for scientists called Prism, which embeds ChatGPT in a text editor for writing scientific papers. The idea is to put ChatGPT front and center inside software that scientists use to write up…
How AI is transforming research: More papers, less quality, and a strained review system - Haas News
Mathijs De Vaan has long recognized the labor required to effectively communicate scientific findings. For the Netherlands native and UC Berkeley Haas associate professor of management, data and analyses are only half the battle; the rest is a time-intensive process of ensuring that complex, nuanced ideas are articulated with the precision that top-tier research demands. […]
Climate-risk scores shape billion-dollar decisions, and new study says science behind them needs to be more transparent
A new paper published in Proceedings of the National Academy of Sciences argues that trustworthiness of climate-risk scores depends not just on the sophistication of the models used to produce the scores but also on whether the science behind them is open, reusable and transparent enough for others to examine, test and improve.
SellYourWay.org Publishes a New White Paper on the Role of Seller Financing in Closing Small Business Sales
Today, SellYourWay.org, a website dedicated to the education of small business owners, is pleased to announce the release of a new, in-depth white paper titled, The Role of Seller Financing in Closing Deals. Lauren Drummond Dale, MCBI, shares expert insights on what seller financing is, how frequently it is used and what small business owners should know before selling their businesses. Ms. Dale is Principal and M&A Advisor at Coastal Consultants, LLC. SellYourWay.org is powered by the Internati