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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!]

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Mar 24 • 2:06 PM EDT • Technology • alineaanalytics.substack.com
Joy Behar skips 'View' interview with Carrie Underwood after criticizing Trump performance

Joy Behar left 'The View' table Tuesday morning, skipping an interview with Carrie Underwood after publicly criticizing the 'American Idol' winner's decision to perform at Donald Trump's inauguration.

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Mar 24 • 1:14 PM EDT • Entertainment • ew.com
When to book summer flights for 2026 as oil prices rise

Rising oil prices and travel disruptions are pushing airfares higher. We asked travel and aviation experts for advice on when to book summer flights.

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Mar 24 • 12:34 PM EDT • Business • businessinsider.com
Melania Trump hosts world counterparts and tech reps to discuss children, education and technology

Melania Trump is calling on nations to work together to improve access to education and technology for children

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Mar 24 • 12:31 PM EDT • Politics • washingtonpost.com
Christal Jordan has the latest in entertainment headlines

Iconic girl groups are going on tour, plus they're an updated on The Bachelorette news.

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Mar 24 • 11:13 AM EDT • Entertainment • fox5atlanta.com
Rubio plans travel to France to sell Iran war to skeptical G7 allies

Secretary of State Marco Rubio will travel to France this week to try to sell America’s skeptical Group of Seven allies on the Iran war that has sent global fuel prices soaring

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Mar 24 • 10:31 AM EDT • Politics • washingtonpost.com
G7 Entertainment Marketing Launches Wild by G7 to Help Destinations Turn Culture Into Travel Demand

New Venture Responds to Surging Demand for Experience-Driven Travel by Helping Destinations Create Cultural Moments that Drive Visitation, Economic Impact, and Brand Loyalty Wild by G7 is producing the Rendezvous Music Festival The Head and the Heart band performed at a past Rendezvous Music Festival in Jackson, Wyoming Wild by G7 Sizzle NASHVILLE, Tenn. and JACKSON, Wyo., March 24, 2026 (GLOBE NEWSWIRE) -- G7 Entertainment Marketing, the experiential and talent booking agency behind campaigns f

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Mar 24 • 9:04 AM EDT • Entertainment • finance.yahoo.com
Tacoma Arts Live, longtime WA arts institution, files for receivership

Tacoma Arts Live, a longtime performing arts organization, has filed for receivership. The court process is similar to bankruptcy. Here's what we know.

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Mar 24 • 9:00 AM EDT • Entertainment • yakimaherald.com
Trump casts Florida mail ballot as he pushes Congress to severely limit that voting option

President Donald Trump has cast another mail ballot in Florida as he continues to publicly bash the voting method as a source of fraud and push Congress to curtail the practice

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Mar 24 • 8:13 AM EDT • Politics • washingtonpost.com
Chris Froome Joins Vekta Leadership Team to Help Shape Sports Performance of the Future

Four-time Tour de France winner Chris Froome to join Vekta as Chief Innovation Officer and Chair of the newly created Vekta Athlete Advisory Board.

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Mar 24 • 8:00 AM EDT • Sports • insider.fitt.co
US whiskey maker takes over Waterford Distillery

Tennessee Distilling Group has agreed to buy Waterford Distillery after the Irish whiskey maker entered into receivership in 2024.

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Mar 24 • 7:13 AM EDT • Business • thespiritsbusiness.com
ICE officers at airports a ‘test run’ for midterms, Steve Bannon suggests

Former White House strategist says current situation at airports will help ‘really perfect ICE’s involvement in the 2026 midterm elections’

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Mar 24 • 6:34 AM EDT • Politics • theguardian.com
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March Madness top seeds dominate: Each No. 1 team's path to Sweet 16

Only one perfect 2026 Women's NCAA Tournament bracket remains as of Monday evening following several upsets, but the top seeds have been chalk.

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Mar 24 • 6:06 AM EDT • Sports • usatoday.com
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RFK Jr. and Dr. Oz have a plan to save rural health care. Here’s the catch.

Top health officials point to AI as the solution for dying hospitals, but experts from rural areas of the country say the solution isn’t that simple.

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Mar 24 • 6:00 AM EDT • Health • washingtonpost.com
'Claude, Resize These Photos' - Anthropic's Agentic AI Will Run Photoshop For You

It can perform boring tasks.

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Mar 24 • 5:46 AM EDT • Technology • petapixel.com
Florida Democrats hope in special election to flip a state legislative district that includes Mar-a-Lago

Democrats in Florida are hoping to capitalize on the party’s recent special election overperformances and come out on top Tuesday in a special state House election for a Palm Beach district that includes President Donald Trump’s Mar-a-Lago residence.

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Mar 24 • 5:00 AM EDT • Politics • cnn.com
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Colorado’s Tamale Act may decide whether home cooks can build a business

An eclectic coalition, including the MAHA call for “food freedom,” gave the law a second chance as backers push for immigrant assistance and entrepreneurship.

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Mar 24 • 5:00 AM EDT • Business • washingtonpost.com
Tropical Cyclone Narelle Crosses Australia

The powerful storm lashed the northern edge of the continent with damaging winds and drenching rain as it made landfall multiple times.

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Mar 24 • 12:01 AM EDT • Science • science.nasa.gov
Advent International Acquires Salt & Stone

The premium body care maker will join the private equity firm’s portfolio, which also includes Olaplex and Parfums de Marly.

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Mar 23 • 11:59 PM EDT • Business • businessoffashion.com
35 Products I Bet You Haven’t Seen Yet, But I Also Bet You’ll *Love*

Nobody panic, but Summer Fridays just released a caramel-vanilla perfume.

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Mar 23 • 9:01 PM EDT • Technology • buzzfeed.com
Scientists say NAD+ could slow aging and fight Alzheimer’s and Parkinson’s

A global team of leading scientists is zeroing in on a tiny but powerful molecule that could reshape how we age. Known as NAD⁺, it plays a crucial role in keeping our cells energized, repairing DNA, and maintaining overall health—but its levels steadily decline over time, potentially fueling diseases like Alzheimer’s and Parkinson’s. Researchers are now exploring ways to boost NAD⁺ using compounds like NR and NMN, with early studies hinting at improvements in memory, metabolism, and physical function.

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Mar 23 • 8:00 PM EDT • Science • sciencedaily.com
Supercomputers just solved a 50-year-old mystery about giant stars

Astronomers have finally cracked a decades-old mystery about red giant stars—how material from their deep interiors makes its way to the surface. Using cutting-edge supercomputer simulations, researchers discovered that stellar rotation plays a powerful role in mixing elements across a previously unexplained barrier inside the star.

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Mar 23 • 8:00 PM EDT • Science • sciencedaily.com
Entertainment and more in the Mid-Ohio Valley

PARKERSBURG – The Artsbridge calendar for this week: TODAY * Geppetto Woodcarver’s Wood Quilt display, 9 a.m. to 4 p.m., WesBanco, Market Street, Parkersburg * Art is Life/Life is Art, ages 55-plus,10:30 a.m. to 12:30 p.m., Parkersburg Art Center * Butterfly Photo Holder, ages 13-plus,11 a.m. to noon, Marietta Public Library * Hygge Club, adults, […]

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Mar 23 • 8:00 PM EDT • Entertainment • newsandsentinel.com
Microsoft Aims to Supercharge Windows Performance and Cut RAM Waste in 2026

Perhaps this would help return some of the goodwill it lost in 2025.

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Mar 23 • 5:38 PM EDT • Technology • pcmag.com
MacBook Neo Silences Critics Over 8GB RAM Being Inadequate; Can Open 60 Apps In Unison While Windows Laptop Powers Off Performing The Same Task

A YouTube channel decided to take the MacBook Neo for an apps stress test and opened up 60 apps at the same time to see if that 8GB RAM will be sufficient

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Mar 23 • 5:31 PM EDT • Technology • wccftech.com
Oura Ring 5 leak reveals design tweaks and Deep Rose finish

The Oura Ring 5 has surfaced in a leak showing design tweaks and colour options. An FCC registration hints the device may launch in 2026.

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Mar 23 • 3:54 PM EDT • Technology • gadgetsandwearables.com
A Jamiroquai Music Video From 1996 Just Inspired A New Revuelto For 2026

Novitec refines the Revuelto with carbon fiber details, new wheels, and a bump in hybrid V12 performance

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Mar 23 • 3:22 PM EDT • Technology • carscoops.com
Fall River's Day of Portugal announces dates, entertainment lineup for 2026

A festival that brings food, faith, and entertainment to the city will be returning once again. Day of Portugal Fall River, which takes place every year at the Gates of the City down near the waterfront on Ponta Delgada Blvd., is back in 2026. One of the more popular events in Fall River which

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Mar 23 • 2:55 PM EDT • Entertainment • fallriverreporter.com
Top business leader demands end to stalemate over City Council's pick for zoning chair

Chicagoland Chamber of Commerce President Jack Lavin said more than 40 development projects have been stalled by City Council's failure to agree on new permanent chair for the powerful Zoning Committee. He wants Mayor Brandon Johnson to forge a compromise to break the stalemate.

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Mar 23 • 2:47 PM EDT • Business • chicago.suntimes.com
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Cheyenne Jackson performs "I'm Feeling Good" on Sunday evening, March 22, 2026, at "Un Salon Moderne à la Nouvelle-Orléans" at the gallery and private residence of Martine Chaisson in New

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Mar 23 • 2:34 PM EDT • Entertainment • nola.com
Rock and roll icon to perform in central Pa. concert this summer

The tour is in support of his new album, “Automatic,” his first original release in five years.

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Mar 23 • 1:49 PM EDT • Entertainment • pennlive.com
Intel Core Ultra 7 270K Plus Review - Intel's Fastest Gaming CPU

The Intel Core Ultra 7 270K Plus is a game-changer, featuring more cores and larger cache than the 265K, while cutting the launch price to just $300. In gaming, it outperformed all non-X3D Ryzen CPUs, and application performance is impressive as well, matching the much pricier Ryzen 9 9950X.

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Mar 23 • 12:57 PM EDT • Technology • techpowerup.com
Intel Core Ultra 5 250K Plus Review - Disrupting AMD's Entry-Level

Intel is breathing new life into its Arrow Lake lineup with the Core Ultra 5 250K Plus. Priced at an attractive $200, this little powerhouse outperforms most AMD CPUs in applications and delivers competitive gaming performance, too. It's a strong contender for budget-friendly builds, and overclocking potential is good, too.

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Mar 23 • 12:57 PM EDT • Technology • techpowerup.com
On eve of SD 14 election, Dems still lag in early vote, but data suggests possible victory in defeat

Even if Democrat Brian Nathan loses, an overperformance could send a big message.

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Mar 23 • 12:20 PM EDT • Politics • floridapolitics.com
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Voice of America Journalists Sue, Saying Trump Officials Interfered in Coverage

The journalists said in the complaint that the administration was trying to force them to be a “mouthpiece” and that one official demanded “loyalty” if reporters wanted to “keep their jobs.”

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Mar 23 • 12:15 PM EDT • Politics • nytimes.com
PC Performance Status Update

An update on the PC performance optimizations Borderlands 4 has received to-date.

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Mar 23 • 11:57 AM EDT • Technology • borderlands.2k.com
While Intel Skipped Core Ultra 9 290K Plus, It Appeared At Geekbench With A Staggering 17% Higher Single And Multi-Core Score Than Ultra 9 285K

Intel's Core Ultra 9 290K Plus scores 3747 single-core and 26117 multi-core in Geekbench, showing a 17% performance boost over the 285K.

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Mar 23 • 11:46 AM EDT • Technology • wccftech.com
Studio Entertainment: The Waddington Brothers

Bismarck, ND (KXNET) — The Waddington Brothers are performing at the Belle Mehus in Bismarck, April 24th at 7:30 pm. Tickets are on sale now and you can find them online by going to bismarcke…

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Mar 23 • 11:45 AM EDT • Entertainment • kxnet.com
Southcoast Community’s Choice Awards business spotlight: Perfect Smiles Dentistry

Nominations for the SouthCoast Community's Choice Awards are rolling in! Don't miss your chance to recognize your favorite local businesses.

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Mar 23 • 11:39 AM EDT • Business • yahoo.com
Causal Inference Is Eating Machine Learning

Your ML model predicts perfectly but recommends wrong actions. Learn the 5-question diagnostic, method comparison matrix, and Python workflow to fix it with causal inference.

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Mar 23 • 11:00 AM EDT • Science • towardsdatascience.com
Peregrine Road performs at the Jesup

BAR HARBOR — On Thursday, April 9, at 5:30 p.m., the Jesup will host a free Music and Conversation program with Peregrine Road (Rachel Bell and Karen Axelrod). Peregrine Road

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Mar 23 • 10:51 AM EDT • Entertainment • mdislander.com
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2nd Car Show Scheduled at Sangertown Square

Racing fans and families can check out high-performance cars and meet local drivers at the Mall Car Show at Sangertown Square.

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Mar 23 • 10:38 AM EDT • Entertainment • wktv.com
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Building a Culture of Health: BJACH Opens Armed Forces Wellness Center at Fort Polk

FORT POLK, La. — Bayne-Jones Army Community Hospital marked a significant step forward in supporting warfighter readiness and community well-being with the grand opening of its new Armed Forces Wellness Center on March 23. The center, located on the first floor inside BJACH, provides Soldiers, Families, civilian employees and beneficiaries with access to personalized health assessments, education and coaching designed to improve overall health and performance.

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Mar 23 • 8:00 AM EDT • Health • dvidshub.net
Report: iPhone Air is about twice as popular compared to the Plus model it replaced

According to cellular network data from Ookla, the iPhone Air is about twice as popular compared to the iPhone 16...

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Mar 23 • 6:53 AM EDT • Technology • 9to5mac.com
Inside the Turmoil at RFK Jr.’s CDC, as Told by Current and Former Employees

Forty-three current and former C.D.C. employees on the changes they say are replacing science with ideology — and making Americans more vulnerable.

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Mar 23 • 5:22 AM EDT • Health • nytimes.com
Rahm Emanuel proposes banning all federal employees from betting on prediction markets

Rahm Emanuel is proposing a far-reaching measure to crack down on betting in predictive markets in Washington as part of an effort to call attention to what he sees as a culture of corruption gripping the nation’s politics

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Mar 23 • 5:00 AM EDT • Politics • washingtonpost.com
Diabetes, Overlooked and Unchecked, Poses New Risks in Africa

As deaths from diabetes start to rival those from infectious threats like malaria, a new form of the condition linked to malnutrition is surfacing in patients who can afford neither screening nor care.

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Mar 23 • 5:00 AM EDT • Health • nytimes.com
A new twist on matter? Strange 'Half-Mӧbius' molecule has rare properties chemists have never seen before

Chemists created a strange 'half-Mӧbius' molecule, where electrons twist freely out of place to make a continuously looping surface.

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Mar 23 • 5:00 AM EDT • Science • livescience.com
The DLSS 5 Backlash Is Still Swirling

Almost a week on, the controversy and backlash over NVIDIA’s DLSS 5 announcement are still swirling, following some mixed messaging from the company about how the tech works. A reveal trailer on Tuesday showcased multiple games like “Resident Evil Requiem,” “Starfield”, and “Hogwarts Legacy” using the new technology, which goes beyond simple upscaling and leads […]

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Mar 22 • 11:26 PM EDT • Technology • darkhorizons.com
A DNA test ruled him out. He was convicted of murder anyway.

Forensics has its share of high-profile problems. There’s phony “junk science,” like bogus bite-mark and blood spatter analyses that have sent innocent people to jail. And there’s the steady drumbeat of lab scandals, where analysts make up results. But there’s a subtler and more pervasive problem at work in many cases: lab analysts and lawyers who take perfectly legitimate science and twist it. Globe Opinion is exploring these distortions with a series we’re calling “Twisted Science.” And there may be no better place to start than with the case of Terrel Barros.

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Mar 22 • 9:57 PM EDT • Science • bostonglobe.com
Apple already has the perfect platform for deploying conversational AI

When Apple initially rolled out Apple Intelligence, the company was pretty openly against the idea of creating a Siri chatbot....

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Mar 22 • 6:10 PM EDT • Technology • 9to5mac.com
Man Born with ‘Butterfly Syndrome’ Is Fighting for Change for ‘the Worst Disease You’ve Never Heard of’ (Exclusive)

Ohio resident Shane DiGiovanna, who has the rare disorder epidermolysis bullosa (EB), is advocating for legislation to help cover costly medical bandages for patients with the disease, which is also known as ‘butterfly syndrome.’

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Mar 22 • 6:00 PM EDT • Health • people.com
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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