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Samsung’s Galaxy A57 gets thinner, faster, and more expensive
Samsung’s 2026 midrangers have arrived.
Political donations in cryptocurrency could be blocked in blow to Reform UK
Government review also recommends political funding from Britons living abroad be capped at about £300,000 a year
How live selling is helping one entrepreneur grow his business
Running a business has been a "roller coaster of a ride," said Scott Wool, who nearly went bankrupt in 2013. Today, he's growing like never before.
5 events in Lancaster County this weekend, from \'Heated Rivalry\' dance party to magic swap meet
Before you make your weekend plans, make sure these events are on your radar.
Woods targets Masters after return to action in TGL
Tiger Woods says he is "trying to play" at next month's Masters after returning to action for the first time in more than a year in the TGL.
Le Bris 'at his brilliant best' to mastermind derby win
Leading up to Sunday's derby at Newcastle, all the talk centred around which of our injured players might be available and it ended up becoming a bit of a distraction from what was actually important - the players who were definitely fit to play their part. While I'm sure Regis le Bris would have loved a fully fit squad, he is not daft enough to get too distracted by the possibilities of having several of his walking wounded involved at the last minute. It meant that while Newcastle were distracted by European football, we were on the training ground figuring out how we were going to walk away from St James' Park with three points.
Congress needs to protect 340B for rural Colorado
By Rod Pelton A lot of politicians talk about understanding what life is like for our rural communities, but not many really do. I’m a third-generation Cheyenne County farmer and rancher; I grew up on the eastern plains of Colorado, raised my family here, and as such am deeply committed to our state’s agricultural communities. I […]
How magnetic is the moon? A new study cracks the long-standing mystery
Researchers believe rock samples taken from the Apollo missions gave scientists a misleading impression
Mike Tomlin Signs With Sports Media Agent Sandy Montag
Sandy Montag and sportscaster-turned-agent Alex Flanagan will represent Mike Tomlin in potential talks with networks and streamers.
The Trump FCC is leveraging public trust for political gain
Tom Wheeler discusses FCC Chairman Carr's recent threat against broadcasters and the broader implications for democracy.
‘R U OK?’ Day bringing awareness to mental health resources in Pitt County
One county in eastern North Carolina is using that question to encourage greater awareness of mental health resources.
Cloudflare’s new Dynamic Workers ditch containers to run AI agent code 100x faster
Cloudflare says dynamically loaded Workers are priced at $0.002 per unique Worker loaded per day, in addition to standard CPU and invocation charges
Marathon has sold 1.2M copies across Steam, PS5, and Xbox
Alinea Analytics estimates show that Marathon has generated gross revenues of $55M via 1.2M copies sold on Steam, PS5, and Xbox: Looking at the split between Steam, PS5, and Xbox, Steam is clearly the main platform for Marathon, accounting for a little under 70% of the audience (800K copies sold). Meanwhile, PS5 takes about 19% (217K) and Xbox (including console, PC, and cloud) accounts for a bit over 11% or 133K. Marathon is technically a first-party Sony title, so seeing the home console struggle to break 20% of the volume is a notable data point for the ongoing platform-agnostic debate. PlayStation Studios online games will almost certainly continue being multiplatform (despite Sony reportedly pulling back on PC releases). Subscribe for free to get the most accurate games estimates in your inbox twice a week 🫶 Subscribe As for Marathon, the consensus among hardcore players who pushed through the awkward onboarding phase – myself included – is that it’s fantastic. The gunplay, aesthetic, and presentation are among the best in the shooter genre. A great game doesn’t always equal an immediate hit, though, as shown by our estimates. Things are looking lukewarm right now. But this might be one of those marathon-not-a-sprint situations. Had to, didn’t I? Why wasn’t Marathon a hit on the same level as Arc Raiders? One topic that came up in a lot of conversations at GDC this year was why Marathon hasn’t hit the same stratosphere as Arc Raiders. On paper, they’re both extraction shooters, and Marathon has the Bungie pedigree – the house that built the gold standard for gunplay in Halo and Destiny. Marathon’s neon-futuristic aesthetic also distinguishes itself from the gritty realism of Tarkov or the post-apocalyptic hope of ARC Raiders. But vibes can only get you so far for first impressions if the onboarding feels like a brick wall. Marathon is a sweaty PvP-focused experience with a first-time user experience and UI that I can only describe as dreadful. Players are dropped into a complex ecosystem where the UI, though visually striking, is functionally uninformative, forcing users to manually hover over nondescript, identical icons just to identify basic gear or weapon mods. This lack of clarity is compounded by punishing mechanics like a severe heat gauge for movement and a scarcity of vital resources, all without a clear tutorial or a low-stakes mode to learn the ropes. Most people – even top streamers and veteran shooter players – have no idea what’s going on in Marathon at first. Arc is on the complete other end of the spectrum. As we covered here and here, Arc Raiders offers a more collaborative, approachable loop where players often work together toward shared goals. And the objectives are instantly clear. To many players, this contrast only emphasised Marathon’s issues, especially during the testing period. Players understand the Arc Raiders loop within 30 minutes, while Marathon acts as a massive filter, chewing up newcomers and spitting them out before they can experience the depth of Bungie’s signature gunplay. What I’m getting at here is that the poor first-time user experience of Marathon’s Server Slam likely stifled launch sales, while the opposite was true for Arc. Let’s look at the pre-launch copies sold for each game during their respective Server Slams (launch-aligned) : Looking at the trajectory: Arc Raiders saw a massive 80% jump in copies sold during its three-day Server Slam (day -13 to -11). Players jumped in, realised the water was fine, and immediately opened their wallets. Marathon, meanwhile, saw a 49% increase in the four days following its Slam (Day -7 to -3). At the time of each game’s respective launch, Arc Raiders had nearly double the Steam footprint of Marathon – and word of mouth only continued to grow. Bungie could have had more time to fix the onboarding process had the beta happened earlier. But Marathon launched three days after the beta finished. These factors limited the launch sales quite a bit, I reckon. Marathon has found a niche audience, though Despite the friction-heavy start, the data suggests that those who survived Marathon’s onboarding are loving life. We’ve been tracking cross-platform DAUs, and while there’s the expected post-launch leakage, many players are sticking with it. After peaking at 478K total DAUs on its first Saturday, Marathon has settled into a respectable rhythm, holding 345K DAUs as of yesterday and averaging 380K DAUs across the weekend. Steam continues to do the heavy lifting here, consistently accounting for the lion’s share of the daily players. Players have been putting in the hours, too: On Steam, Marathon’s average playtime has climbed to 27.8 hours, significantly outpacing the console averages on PS5 (16.5h) and Xbox (17.3h). Even more telling than the averages: 22% of the Steam audience has surged past the 50-hour mark, and nearly 7% have already logged over 100 hours. Subscribe for free to get the most accurate games estimates in your inbox twice a week 🫶 Subscribe This data suggests that once the Bungie magic clicks, it hooks players deeper than the average extraction shooter. There’s also started to be a shift in the game’s discourse. Marathon launched as one of those games that’s cool to hate. But as Marathon’s 100-hour club grows, we’re seeing conversations around its mechanical merit outweigh the negativity. Several high-profile creators, who were initially vocal critics, have spent the last week coming around on the mechanical depth of the endgame. It’s a subtle but positive signal; the hate train is losing steam, and a new narrative about the game is emerging. Bungie faithfuls unite Another interesting metric in Marathon’s first few weeks is who, exactly, is playing. Bungie leans heavily on its prestige as the “makers of Halo and Destiny,” in its marketing, and that message has clearly hit the mark. On Steam, the gravity (hammer) of Bungie’s previous work is unavoidable. A staggering 78.2% of Marathon players also played Destiny 2. The trend carries across other platforms, with 74.2% of PS5 players and 82.7% of Xbox players also having played Destiny 2. The Halo legacy lives on, it seems. More on that in a bit. While Destiny 2 went free to play, these numbers still represent a high-intent migration of a fanbase that trusts Bungie’s specific brand of kinetic gunplay and cryptic world-building. The Xbox data adds another layer of legacy. About 85.7% of Marathon players on Xbox have played Halo Infinite, while over half of the Steam audience has spent time in Halo Infinite and 36.1% in the Master Chief Collection (a paid collection of the old Bungie-made legacy games). Interestingly, we see a 55.9% overlap with ARC Raiders on Steam. Overlap is even higher there on PlayStation (60.5%) and Xbox (66.5%). And there’s also significant crossover with Helldivers 2 on all platforms, too. Subscribe for free to get the most accurate games estimates in your inbox twice a week 🫶 Subscribe Bungie has found some of its fans with Marathon, and the challenge now is keeping this engaged in a high-stakes PvP environment when they’ve spent the last decade primarily enjoying the power fantasies of PvE. On that note… Go the full 26 miles? Or cut and run? Time for some could’ve, should’ve, would’ve. These things would have improved Marathon’s performance at launch: A more robust onboarding process, perhaps in the form of a short single-player/PvE campaign. We know Bungie fans love this stuff. A traditional arena-based mode akin to Destiny’s Crucible could have been a bridge for the cautious players who’d have been otherwise deterred by the Server Slam. It’s also a great palate cleanser after getting merked. Introducing a dedicated PvE environment would have similarly diversified the conversation and lowered the barrier for the Bungie faithful who found the pure PvP extraction loop too abrasive. PvE is safer than PvP these days. There’s an argument that a thin PvE mode would have just felt like a budget Destiny, potentially hurting the brand more. But given how dire the FTUE is, I think it would have been a net positive. Any kind of tutorialised loop that demystifies the stakes, really. While there is merit in a studio sticking firmly to a singular creative vision, and going all in on the hardcore extraction loop. Less forgiving is the technical reality is that the user interface and first-time user experience (FTUE) were not at a commercial standard for launch. Subscribe for free to get the most accurate games estimates in your inbox twice a week 🫶 Subscribe In a landscape where player time is oversaturated and the most contested currency, a flawed FTUE is a critical failure point. But it’s not all doom and gloom, as Marathon has an incredible, unique gameplay loop, suggesting that financial success is still attainable if Bungie can pivot effectively. Bungie and PlayStation now face a difficult strategic crossroads, though – one within a challenging games market. They could: Double down on Marathon with a long-term Rainbow Six Siege- or No Man’s Sky-style recovery plan, which is something I heard Last Stand Media’s Chris Maldonado mention last week. While this could be a sunk-cost fallacy in action, it could eventually yield the audience the game’s mechanical depth deserves. Shift focus toward the inevitable Destiny 3 or another project, mitigating the escalating opportunity cost and cutting their losses, so to speak. Doing both is an expensive proposition, given the high overhead and burn rate of operating out of Bellevue, Washington. With Sony recently demonstrating a lower threshold for underperforming studios and projects, the margin for error has vanished. Whatever happens, the next six months will determine whether Marathon becomes a cornerstone of Sony’s live-service portfolio or a cautionary tale of vision exceeding accessibility. I’m hoping it’s the former, because Marathon rocks. As always, hit subscribe to get updates on Marathon and other relevant games. Subscribe Want to get your hands on our data for yourself – for free? We’re offering a free trial of our platform for games companies. Send us a message here, or reply to this email, and we’ll set you up. The last word Reply to this email – or reach out here – if you have any feedback for the newsletter – or want to request a game for us to cover. [Alinea Analytics boasts the most accurate PC and console estimates in the business. Game makers use our platform to understand their audience, keep an eye on the competition, monitor sales trends, and spot new opportunities. We equip game studios and financial institutions with accurate data and the confidence to make smarter, data-driven decisions. Want to talk about all things games market data? We’d love to chat!]
A rare active volcano on Mars may be causing the whole planet to spin faster
Data from NASA's InSight mission suggests the Red Planet's Tharsis region is more active than previously thought and may be why Mars is spinning more quickly over time.
Scottie Scheffler withdraws from Houston Open, likely won't play again until 2026 Masters
The World No. 1 withdrew from his Masters tune up event on Tuesday
From The Sports Desk: NBA playoff push
The Orlando Magic and Cleveland Cavaliers face each other on Tuesday in a game between two Eastern Conference teams hoping to salvage disappointing seasons.
Ed Davey accuses Reform UK and Tories of importing ‘Trump-style divisive politics’
Lib Dems will focus on ‘rolling up their sleeves and getting things done’, leader says at launch of local election campaign
Why going to an HBCU might be better for Black students’ health
A study found correlation between the environment and long-term wellness in sample of 1,978 who attended college between 1940-80
Holland & Knight Health Dose: March 24, 2026 | Insights
Congress faces a tight deadline on DHS funding and the SAVE Act as Easter recess nears, while healthcare hearings continue amid uncertainty.
US democracy has settled into diminished state, experts find
Bright Line Watch researchers see stabilization in democratic health but at lower levels after sharp decline
‘Corpus Christi’ returns to the Bartell, years after protests
StageQ, Madison’s LGBTQ community theater, stages Terrence McNally’s controversial retelling of Jesus’ life and crucifixion through Easter weekend.
Scientists Discover Alaska Glaciers Are Melting Weeks Longer Than Expected
New radar data reveals Alaska’s glaciers are melting longer and reacting faster to heat.
Josh Shapiro endorses James Malone in key Lancaster County Senate race
Gov. Josh Shapiro has officially endorsed James Malone’s bid for reelection in the Lancaster County state Senate district that both parties say could determine party control next year.
As winters warm, Minnesotans grapple with climate grief
Winters in Minnesota are warming faster than any other season. That’s jeopardizing seasonal traditions in the state — and mental health experts say that takes a toll on mental health.
An asteroid sample contains all the key components for life on Earth
DNA from a distance
Victorian business fined for telling influencers to lie about paid Instagram post in first of its kind penalty
Watchdog also fines PhotobookShop for editing a paid review from an influencer who had described process as ‘fiddly’
NIU Today - Two business graduate degrees reimagined with a bold AI focus
Beginning this fall, two graduate degrees within the College of Business’s Department of Operations Management and Information Systems (OM&IS) will be reimagined to emphasize their focus on artificial intelligence and analytics. Formerly known as the Master of Science in Data Analytics (MSDA) degree, this degree has been transformed into the Master of Science in Business...
WHO recommends new diagnostic tools to help end TB
On World TB Day, the World Health Organization (WHO) is urging countries to accelerate action to end tuberculosis (TB) and expand access to lifesaving services by using new innovations such as diagnostic tests that can be used near the point-of-care and tongue swabs that can help detect the disease faster reaching more people.
Science Through Shadows: How Astronomical Alignments Reveal the Universe
When one celestial object passes in front of another, it can cast a shadow that travels across space – and sometimes across Earth. These moments of alignment, known as eclipses, occultations, and transits, allow scientists to study distant objects in remarkable ways. By observing how light changes when an object briefly blocks another, astronomers can measure sizes and shapes, detect atmospheres, and refine the orbits of asteroids and planets.
Manor Township Democratic committee person kicked off May 19 primary ballot
Kirk Barrett, a candidate for a Manor Township seat on the Lancaster County Democratic Committee, has successfully kicked the incumbent’s name off the ballot for the upcoming May 19 primary.
2026 NCAA Tournament second round schedule: March Madness bracket, game dates, tip times, TV channels
Check out the master schedule for the first and second rounds of the 2026 NCAA Tournament so you can watch all the March Madness
Bipartisan Senate bill would ban sports betting on online prediction markets
Bill was introduced in the Senate on Monday as prediction market companies face greater scrutiny on state level
Antarctica could warm 1.4 times faster than the rest of the Southern Hemisphere in the coming decades, study finds
Antarctica could warm much faster than its surroundings over the next few decades due to a phenomenon known as polar amplification that is well established in the Arctic.
Trump sued by historic preservation groups to block Kennedy Center changes
A coalition of preservation groups is suing to stop major physical changes at the Kennedy Center under President Donald Trump’s renovation plans. On Monday, the groups filed a lawsuit against
Intel Core Ultra 7 270K Plus & Core Ultra 5 250K Plus Official Benchmarks: Faster Than 14900K & Comparable To Ryzen X In Gaming, Much Faster In Apps, Superb Value
Intel shared official benchmarks of its Core Ultra 7 270K Plus & Core Ultra 5 250K Plus in gaming, apps, and more, against AMD Ryzen CPUs.
Add this one line to your AI prompts for faster, better answers
This handy prompt add-on can save you from tedious back-and-forths with your AI.
Cycling, crystals and cutting-edge science: the secrets of Hodgkinson and Hunter Bell’s success
The training duo who oversaw famous medal success in Torun believe the best is yet to come for their athletes
Data Is at the Heart of What Public Health Does
Data is key to protecting the health and safety of a community, from identifying and tracking disease outbreaks to ensuring that water is safe to drink. Data is also vital to understanding where resources are most needed. This value is especially apparent to the officials charged with protecting public health, such as Dr. Janet Berreman, Kauai’s (Kauaʻi’s)* district health officer.
Starmer says ‘every lever’ will be explored to ease rising costs of living from Iran conflict
PM will chair Cobra meeting with key ministers and Bank of England on Monday, as experts warn of economic shock
Trump whistleblower Alex Vindman: ‘Sitting on the sidelines was not an option’
Democratic Senate hopeful says experience of being key witness in Trump’s first impeachment makes him right choice for Florida
Why the BTS Comeback Concert Was a ‘Disaster’ for Some Businesses
The turnout for the K-pop titans’ show was much lower than projected by officials, hitting the bottom line of some restaurants. Shares in the group’s management company also fell.
Small swings, high drama: why UK polls are less volatile than they seem
In what is beginning to look like a fragmented five-party system, small swings carry outsized political consequences
‘Anyone but Labour’ or ‘anyone but Reform’? Clash of animosities likely to define May local elections
While Labour braces for a rout that could see off Starmer, a rising drive to keep out Farage is complicating expectations
What’s at stake for UK in May’s local elections: six key questions
Reform, Plaid Cymru, the SNP and the Greens are all banking on big gains and nationwide repercussions
AI Swarm Attacks Are Coming, Is Your Business Ready?
Leaders need a new cybersecurity playbook for the agentic era, with stronger governance, faster response systems, workforce awareness, and up-to-date security frameworks.
Breaking the Cycle review – meet the charismatic Thai politician striving to change his country’s history
Gripping documentary examines the Future Forward Party’s unprecedented 2019 election result, and its leader’s aim to break Thailand’s repeated military coups
Funding for populist-right ‘media-political complex’ exceeded £170m in five years, research finds
Handful of billionaires gave huge sums in particular to media organisations that boosted rightwing politicians, says Liam Byrne MP
Surging Hawks look to take advantage of short-handed Grizzlies
The streaking Atlanta Hawks will try to enhance their push for playoff positioning in the Eastern Conference when they host the struggling Memphis Grizzlies on Monday.
Third annual 'Hop into Health' draws families for free screenings and Easter fun
In Jacksonville Sunday afternoon, Onslow Memorial Hospital hosted a fun and free opportunity for families to enjoy activities like an Easter egg hunt, and take
Luke Doncic facing suspension as Lakers oppose playoff-bound Pistons
The Los Angeles Lakers barely kept their winning streak alive on Saturday. They'll go for 10 in a row when they visit the Eastern Conference-leading Detroit Pistons on Monday.
Midtown's '42 Below' retail occupancy rising faster than the rest of Manhattan
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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