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Samsung restocking Galaxy Z TriFold on April 10 in US stores and online
Samsung will restock the Galaxy Z TriFold, presumably for the final time, on April 10 in the US both online...
Restock Alert: Galaxy Z TriFold Returns This Friday
In two days, Galaxy Z TriFold returns. Surprising to some, as it was reported that Samsung was discontinuing this phone after stocking it online only one time, April 10 on... #Android #GalaxyZTriFold
Apple very cautious about iPhone Ultra sales; Samsung wins concession
A new report suggests Apple is being extremely cautious in its expectations of demand for its most expensive ever smartphone,...
Apple’s 2026 Shake-Up: iPhone 18 Pro Leaks While iPhone Fold Steals The Show
Which iPhone flagship should you be waiting for? This September’s launches will be unlike any previous year.
Apple’s Foldable iPhone Remains on Track for September Debut
Apple Inc.’s first foldable phone is on track to arrive during the company’s normal iPhone launch period later this year, people with knowledge of the matter said, rebutting concerns about major manufacturing snags.
Satechi’s 3-in-1 travel stand now wirelessly charges your phone at 25W
The upgraded version of Satechi’s folding multi-device charger gets a design update and support for Qi2.2.
Report: Apple's foldable iPhone may be delayed due to engineering snags
Apple has reportedly run into "more issues than expected" with its foldable iPhone that may delay its release.
Apple’s 2026 Shake-Up: iPhone 18 Pro Leaks While iPhone Fold Steals The Show
Which iPhone flagship should you be waiting for? This September’s launches will be unlike any previous year.
Samsung updates One UI software rollout roadmap
On March 6, Samsung shared its April 2026 software rollout roadmap. It’s important information for every Galaxy device user. The company has made some notable changes in this month’s roadmap, compared to March 2026. Current Models for Monthly Security Updates Samsung offers new security updates to premium Galaxy phones and foldables on a monthly basis. […]
Apple's foldable iPhone encounters engineering snags, faces potential shipment delays, Nikkei Asia reports
Apple has been encountering setbacks in the engineering test phase of its first foldable iPhone, which could lead to delays in its mass production and product shipment schedule, Nikkei Asia reported on Monday, citing sources.
Foldable iPhone hits engineering snags, shipment delays possible: sources
April-May 'extremely critical' period for Apple to resolve issues in time
iPhone Fold Enters Trial Production Phase Ahead of 2026 Launch
Apple partner Foxconn has started trial production on the iPhone Fold, according to Chinese leaker Instant Digital. Trial production comes before mass production, which Apple plans to start in July as long as no issues come up during the earlier testing stage. So far, Apple remains on track to launch the iPhone Fold in 2026, though the latest rumors suggest that it's not going to come out in September. Instead, it could launch sometime after the iPhone 18 Pro, debuting as late as December.
Apple’s folding iPhone redesign looks stunning in new images
Get a fresh look at the upcoming folding iPhone, as leaked images reveal a refined camera design and sleek back panel.
Galaxy Z Fold ‘Wide’ will be easier to handle as One UI 9 leaks spout
Samsung’s Galaxy Z Fold “Wide” has been touched on in previous leaks, though recent One UI 9 screenshots add some...
Samsung’s new Galaxy Z Wide Fold has already won customers over
Samsung's new Galaxy Z Wide Fold isn't even out yet and people are clamoring to get their hands on it.
iPhone Fold just hit major milestone that’s good news for launch timing
The iPhone Fold is coming this year, and per a leaker, the brand new model just hit a major milestone that’s good news for launch timing.
Apple’s foldable iPhone is now a reality
The long-awaited foldable iPhone is now a reality and we can expect photos of working units soon.
Lawmakers seek permanent funding for referral hotlines connecting families to mental health care
A bill heard by a Rhode Island Senate panel last week would fold funding for telephone hotlines used by pediatricians and family doctors to connect kids and parents to mental health treatment hotlines into a health department program funded by insurer contributions.
iPhone Fold rumor suggests it will bring a 3D printed hinge
This is the same tech used on Oppo’s Find N6. A new report from China is confident that the upcoming iPhone Fold will feature a 3D printed hinge to help...
Samsung Galaxy Z Fold 8 Leaks: 5,000mAh Battery and 45W Charging Finally Confirmed?
Massive Samsung Galaxy Z Fold 8 leaks reveal a game-changing "Wide" variant with a 3:4 aspect ratio, 5,000mAh battery, and 45W charging
A Grip on Sports: A Hall of Fame weekend has unfolded in Spokane, though neither NCAA men's semifinal games reached that level
A GRIP ON SPORTS • Where were we? Oh, yes. Celebrating an incredible spring weekend with the thought basketball rocks. And “Roundball Rocks” as the soundtrack.
Nearly launched LG Rollable smartphone reveals its innovative internals in teardown video
Even Samsung’s 2026 foldables pale in comparison. If LG had not decided to exit the smartphone business, we could have seen a first rollable smartphone as early as 2021, one that was already more innovative five years ago than anything the foldable phone segment has produced recently, as a teardown shows.
New Samsung Images Confirm Galaxy Z Fold 8 ‘Wide’ Details
New images, directly from Samsung, confirm the existence of the Galaxy Z Fold 8 'Wide' and its new display design.
Gemma 4 and what makes an open model succeed
Having written a lot of model release blog posts, there’s something much harder about reviewing open models when they drop relative to closed models, especially in 2026. In recent years, there were so few open models, so when Llama 3 was released most people were still doing research on Llama 2 and super happy to get an update. When Qwen 3 was released, the Llama 4 fiasco had just gone down, and a whole research community was emerging to study RL on Qwen 2.5 — it was a no brainer to upgrade. Today, when an open model releases, it’s competing with Qwen 3.5, Kimi K2.5, GLM 5, MiniMax M2.5, GPT-OSS, Arcee Large, Nemotron 3, Olmo 3, and others. The space is populated, but still feels full of hidden opportunity. The potential of open models feels like a dark matter, a potential we know is huge, but few clear recipes and examples for how to unlock it are out there. Agentic AI, OpenClaw, and everything brewing in that space is going to spur mass experimentation in open models to complement the likes of Claude and Codex, not replace them. Especially with open models, the benchmarks at release are an extremely incomplete story. In some ways this is exciting, as new open models have a much higher variance and ability to surprise, but it also points at some structural reasons that make building businesses and great AI experiences around open models harder than the closed alternatives. When a new Claude Opus or GPT drops, spending a few hours with them in my agentic workflows is genuinely a good vibe test. For open models, putting them through this test is a category error. Something else to be said about open models in the era of agents is that they get out of the debate of integration, harnesses, and tools and let us see close to the ground on what exactly is the ability of just a model. Of course, we can’t test some things like search abilities without some tool, but being able to measure exactly the pace of progress of the model alone is a welcome simplification to a systematically opaque AI space. Share The list of factors I’d use to assess a new open-weight model I’m considering investing in includes: Model performance (and size) — how this model performs on benchmarks I care about and how it compares to other models of a similar size. Country of origin — some businesses care deeply about provenance, and if a model was built in China or not. Model license — if a model needs legal approval for use, uptake will be slower at mid-sized and large companies. Tooling at release — many models release with half-broken, or at least substantially slower, implementations in popular software like vLLM, Transformers, SGLANG, etc due to pushing the envelope of architectures or tools. Model fine-tunability — how easy or hard it is to modify the given model to your use-case when you actually try and use it. The core problem is that some of these are immediately available at release, e.g. general performance, license, origin, etc. but others such as tooling take day(s) to week(s) to stabilize, and others are open research questions — with no group systematically monitoring fine-tunability. In the early era of open models, the days of Llama 2 or 3 and Qwen pre v3.5, the architectures were fairly simple and the models tended to work out of the box. Some of this was due to the extremely hard work of the Llama, Qwen, Mistral, etc. developer teams. Some is due to the new models being genuinely harder to work with. When it comes to something like Qwen 3.5 or Nemotron 3, with hybrid models (either gated delta net or mamba layers), the tooling is very rough at release. Things you would expect to “just work” often don’t. I’ve been following this area closely since we released Olmo Hybrid with a similar architecture, and Qwen 3.5 is just starting to work well in the various open-source tools that need to all play nice together for RL research. That’s 1.5 months after the release date! This is just to start really investing more into understanding the behavior of the models. Of course, others started working on these models sooner by investing more engineering resources or relying on partially closed software. The fully open and distributed ecosystem takes a long time to get going on some new models. All of this is lead-in for the most important question for open models — how easy is it to adapt to specific use-cases? This is a different problem for different model sizes. Large MoE open-weight models may be used by entities like Cursor who need complex capabilities in their domain, e.g. Composer 2 trained on Kimi K2.5. Other applications can be built on much smaller models, such as Chroma’s Context-1 model for agentic search, built on GPT-OSS 20B. The question of “which models are fine-tunable” is largely background knowledge known by engineers across the industry. There should be a thriving research area here to support the open ecosystem model. The first step is to understand characteristics of different base and post-trained models to understand what they look like. The second step is to tune pretraining recipes for open models so they’re more flexible. Interconnects AI is a reader-supported publication. Consider becoming a subscriber. Subscribe For The ATOM Project and other Interconnects endeavors, we’ve put in substantial effort to measuring adoption trends in the open ecosystem. Everything takes a long time to unfold after a model is first publicly available — and adaptability is why. What we know for sure now, when Qwen has been going from strength to strength with its releases, is that technical staff across the industry has gotten comfortable working with Qwen models. Countless research methods and datasets were made to work with Qwen. It’ll take patience for any other model family to get to this point — a patience I’m not sure many open model builders have. This takes us to Gemma 4, Google’s latest open models. Gemma 3 was released more than a year ago, in March of 2025, and is a bit underrated. Gemma 4 comes in 4 sizes for now, with a bigger, MoE model of over 100B total parameters rumored but not released yet. The models we have today come in sizes of ~5B dense, 8B dense, 26B total 4B active MoE, and 31B dense. I’m most excited that they’re finally adopting a standard Apache 2.0 open source license. This’ll massively boost adoption. The standard of better licenses for strong open-weight LLMs was set by mostly Chinese open model labs in the last 1-2 years, and now U.S. companies are following suit. I will personally be so happy if the horrible Llama licenses and Gemma terms of service were an ~18-month transient dynamic of the industry being nervous about releasing strong open models. The Gemma 4 scores look very solid, the small models have incredible benchmark scores (especially in general domains like LMArena) and the 31B model rivals the recent Qwen 3.5 27B, which is the leading member of that class. The ~30B size range is an important one, as it’s accessible both to researchers and to enterprises looking to deploy the model in real use-cases. Where the 7B model scale is the default for tinkering and research, a 30B model is the default for seeing if an open model can unlock substantial value in your specific workflow — a good mix of intelligence, low price, tractability for downstream training, etc. This takes us back to the above adoption criteria I mentioned for open models and the bigger question — do I think Gemma 4 will be an overwhelming success? Previous Gemma models have been plagued by tooling issues and poorer performance when being finetuned. Gemma 4’s success is going to be entirely determined by ease of use, to a point where a 5-10% swing on benchmarks wouldn’t matter at all. It’s strong enough, small enough, with the right license, and from the U.S., so many companies are going to slot it in. I’m cautiously optimistic that Gemma 4 is going to work better here. Winds are shifting for open models built in America. We saw GPT-OSS go through a bumpy launch to become an overwhelming success. There’s a collective energy around the likes of Reflection, Arcee, Nemotron, Gemma, Olmo, and peers that show substantial demand for building new stacks around open models. There’s capital to be spent on AI stacks across the economy by those who want more ownership of everything, including the model. After launching The ATOM Project 240 days ago, the conversation is shifting into the next stage. Summer of 2025 was a crisis moment where the U.S. AI scene realized it can’t wait and figure out open models after building AGI. The two markets will capture different areas and proceed in parallel. Now that more companies in the U.S. are releasing strong models, we need to improve the ecosystem so that these models are easy to use, understand, and build value around. It’s the hard work to build another inflection point in these adoption plots I’ve been updating consistently, but that’s the work to be done. Join me in it. More data coming soon! Here’s a sneak peek:
One UI 9 reveals Galaxy Z Wide Fold’s wider screen
Samsung is working on a Galaxy Z Fold series device with a wider foldable screen, and One UI 9 has revealed more information about it.
Pixlel 11 Pro XL renders show Google going all-in with new camera bar
Pixel 11 Pro XL renders complete our preview of this year's non-foldable models.
Research roundup: 7 cool science stories we almost missed
Sperm gets lost in space; raccoons solve puzzles; the physics of folding a crepe; and more.
Exclusive: Google Pixel 11 Official CAD Renders & Rumors
The Google Pixel 11 is set to be released later this Summer, a bit later than the Galaxy Z Fold 8 and Galaxy Z Fold 8 Wide, which we leaked last week.
Liverpool urged to give more opportunities to young midfielder
Liverpool’s Next Midfield Evolution: Nyoni Emerging as Endo’s HeirLiverpool’s midfield has undergone a steady recalibration in recent seasons, but the next phase may already be unfolding in plai...
2026 Cook Out 400 predictions, odds, start time: NASCAR at Martinsville picks, best bets by proven model
Best bets for NASCAR at Martinsville as the 2026 Cook Out 400 unfolds on Sunday with Tyler Reddick atop the Cup Series standings
Motorola reveals when pre-orders will start for the Razr Fold in one country
A tweet from Motorola makes it clear when buyers can start to reserve their Razr Fold in this one country.
Science, mapping and art collide at ArtReach
A river story unfolds at ArtReach St. Croix with the opening of two exhibitions, Deep Mapping and Valley Pottery: 2,000 Years. Both exhibitions show a deep love for the valley
Where’s One UI 8.5 beta for Galaxy S25 Edge?
The past week was a joy ride for the One UI 8.5 beta program, with more Samsung devices joining the test phase, but without the Galaxy S25 Edge. The Galaxy S25 FE, S24, S24+, S24 Ultra, S24 FE, Fold 6, Flip 6, Tab S11 series entered the beta in the latest round. Despite being limited […]
Motorola teases Razr Fold pre-orders that start pretty soon
The Motorola Razr Fold looks like a pretty exciting new foldable, and impressive as Motorola’s first book-style entry. Its release...
Anker's New Prime 3-in-1 Foldable Charging Station Hits $104.99 Low Price on Amazon
Anker's new Prime 3-in-1 Wireless Charging Station has been marked down to $104.99 during Amazon's Big Spring Sale, down from $149.99, with no need for a coupon. This accessory just launched last month, and Amazon's sale today represents a new all-time low price. Note: MacRumors is an affiliate partner with some of these vendors. When you click a link and make a purchase, we may receive a small payment, which helps us keep the site running.
'A muzzle on elected officials': NDAs 'cloak' Louisiana's biggest business developments
Louisiana officials signed non-disclosure agreements as Amazon's $12 billion data centers unfolded in secret.
Motorola’s next Razr Ultra is even thicker in first leak, and it makes me want to scream
Motorola is making its next Razr Ultra even thicker than the last one, despite the trend of slimmer and slimmer foldables.
Motorola Razr 70 Ultra leaks on high-resolution renders for the first time
The Motorola Razr 70 Ultra can be seen for the first time in high-resolution render images. Motorola's next-generation folding flagship combines a 4-inch secondary display with slim bezels with a 7-inch main display and a dual camera.
iPhone Fold is ‘no doubt’ coming later than iPhone 18 Pro, says Gurman
Bloomberg’s Mark Gurman said today there is “no doubt” the iPhone Fold will ship a bit later than the iPhone 18 Pro.
iPhone Fold Likely to Ship Later Than iPhone 18 Pro
The new foldable iPhone won't ship to customers in the same September timeframe as the iPhone 18 Pro and iPhone 18 Pro Max, Bloomberg's Mark Gurman said today in a Q&A session. Apple will likely ship the iPhone Fold to customers after the iPhone 18 Pro and Pro Max come out in September, but Gurman did not provide a specific availability timeline.
My brief, weird time with the Samsung TriFold
A funny thing happened on the way to the TriFold.
One UI 8.5 Beta Program is expanding to more Galaxy devices
After releasing One UI 8.5 beta to the Galaxy S25, Galaxy Z Flip 7, and the Galaxy Z Fold 7, Samsung is expanding it to more Galaxy devices.
Samsung Brings One UI 8.5 Beta Programme to More Galaxy Devices
Samsung is expanding the One UI 8.5 beta programme to additional Galaxy devices. Introduced with the Galaxy S25 series, Galaxy Z Fold7 and Galaxy Z
WHO warns of health crisis ‘unfolding in real time’ across Middle East
Hostilities should halt and healthcare facilities must be treated as ‘safe havens’, WHO’s regional chief has said
Anker Smart Display 45W USB-C Foldable Charger Drops 30%, Small in Size and Smaller in Price
It's 47% smaller than most chargers, but doesn't compromise on performance.
As March Madness unfolds, NY Fed highlights sports betting toll on consumer credit health
As sports gambling becomes more popular and less restricted, consumer credit health is suffering, according to a new report by the New York Fed.
As March Madness unfolds, NY Fed highlights sports betting toll on consumer credit health
As sports gambling becomes more popular and less restricted, consumer credit health is suffering, according to a new report by the New York Fed.
Exclusive: Samsung Galaxy Z Fold 8 Wide Official CAD Renders & Rumors
Samsung is planning a second book-style fold for later this year, specifically to compete with the upcoming iPhone Fold. Apple is said to be launching a
🥐 Mbappé case, auditions at Barça... Wednesday's 5️⃣ top stories
Attention, Spain’s folders, cards, and notebooks. This Wednesday, March 25, 2026, dawns with pulses racing both in the offices and on the pitch.The news forces us to take a close look at the Valdebe...
Exclusive: Samsung Galaxy Z Fold 8 Official CAD Renders & Rumors
This is the Samsung Galaxy Z Fold 8. After a pretty huge upgrade last year, for the Galaxy Z Fold 7, Samsung doesn't appear to be making any massive
Galaxy Z Fold 8 specifications leak again
Samsung is expected to launch the Galaxy Z Fold 8 in July 2026, and its specifications have allegedly leaked ahead of the launch event.
Lithia sports facility proposal sparks heated zoning battle between neighbors, supporters
A growing dispute is unfolding in Lithia, where a proposed private youth sports complex is drawing strong reactions from both neighbors and supporters.
Ecological and demographic drivers of Oropouche virus transmission
Nature Health - Nationwide analysis of 30,086 confirmed Oropouche virus cases in Brazil between 2014 and 2025 shows that rural municipalities had over 11-fold-higher incidence than urban areas and...
Apple Reportedly Preparing 'Biggest Set of iPhone Revamps' Ever
Apple is working on "the biggest set of iPhone revamps in the product's history," according to the latest word from Bloomberg's Mark Gurman. Specifically, he is referring to the long-rumored foldable iPhone, as well as an ambitious 20th-anniversary iPhone with a truly "edge-to-edge" design.
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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