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Anna Faris reacts to Chuck Lorre’s claim he hesitated casting her on ‘Mom’: ‘Of course it hurts’
Anna Faris has broken her silence on Chuck Lorre’s claim that he was ‘correct’ to feel ‘reluctance’ over casting her on ‘Mom,’ saying, ‘Of course it hurts’ on social media. ‘I’m proud of what we made together.’
Yankees should make obvious $10 million David Bednar decision
The Yankees should not hesitate to do this.
Pentagon draws up new Iran strike plans as Trump hesitates
The U.S. military has drafted options for three days of strikes, but in recent months the president has repeatedly vetoed plans to restart the war.
Calvert's Science Scores Climb, but Eighth Grade Won't Budge
Where Calvert County students shine, they shine. High school government students have finished first in Maryland for the fourth straight year, 30 points above the state. Where they are stuck, the school board did not hesitate to ask why. Calvert County Public Schools officials gave the Board of Education the district’s 2026 MCAP results in […]
From the Mayor’s Desk: Politics and transparency
Election time is upon us again. If you are like my family, you may find many of the ads, flyers, and TV commercials to be unbelievably negative and false. This robs us of good candidates by making people who are considering running for office hesitate to do so. Excuses such as “Someone else who supports […]
Eagles Coach Unleashes Truth On Makai Lemon’s Debut vs Commanders
Despite missing Makai Lemon for a chunk of training camp, the Philadelphia Eagles didn’t hesitate to start the rookie in Sunday’s Week 1 action against the Washington Commanders. Lemon was the third wide receiver alongside DeVonta Smith and Dontayion Wicks, and the Eagles attempted to draw up some plays to get him going early. Unfortunately, […] The post Eagles Coach Unleashes Truth On Makai Lemon’s Debut vs Commanders appeared first on HEAVY.
Vinicius Junior hesitates on Real Madrid renewal amid Arsenal push
Vinicius Junior is reportedly not particularly keen on renewing his contract with Real Madrid, with Arsenal fully aligned on trying to lure him to north London.Photo by Judit Cartiel/Getty ImagesAt th...
Science-based testing powers better health at Plus10 - Cross Timbers Gazette | Southern Denton County | Flower Mound
Flower Mound resident Yves Lafortune has competed in his fair share of Ironman events, 100-mile runs, and national-level triathlons over the years. And if you ask him if he plans to do more, he wouldn’t hesitate to say yes. Clearly, the challenge isn’t finding the passion or commitment to keep going. As a lifelong athlete, […]
McConnell says a fall led to his hospitalization, breaking weeks of silence about health condition
McConnell, 84, explained the long silence about his condition by saying that “folks of my generation often hesitate to share the vulnerability that comes with growing older.”
McConnell says a fall led to his hospitalization, breaking weeks of silence about health condition
McConnell, 84, explained the long silence about his condition by saying that “folks of my generation often hesitate to share the vulnerability that comes with growing older.”
The Case For Harold Fannin Jr. In 2026
Kevin Tompkins lays out the bull case as to why fantasy managers should not hesitate to aggressively draft Harold Fannin Jr. in 2026.
Peterson didn’t hesitate in calling James the GOAT
Peterson didn’t hesitate in calling James the GOAT
The work you can't always see: Beer is political, part 2
Recently I published a piece about beer, politics, and the question of who speaks up and who doesn’t. I meant every word of it. I still do. And then my inbox opened up. Cleveland Prost is a reader-supported publication. To receive new posts and support my work, consider becoming a free or paid subscriber. Subscribe I’ve been writing about beer since 2014. For most of that time, I kept things deliberately light — taproom profiles, new releases, the people behind the pints. Gradually, over years of building this thing, you gave me something I didn’t expect: permission. Permission to go deeper. To say what I actually saw in this industry and what I actually believed about it. That trust isn’t something I take lightly. It’s why that piece existed at all, and it’s why this one does too. I’m not walking anything back. But I want to go further. In that piece, I wrote that beer has never existed outside the system. That immigration policy affects who staffs breweries and harvests ingredients. That labor policy affects taproom workers. That civil rights policy affects who feels safe walking into a taproom. That “beer does not exist in a vacuum. The idea that it does is comforting. It is also false.” I believe that as much now as I did when I wrote it. But one idea came back at me, in different forms, over and over (from reader emails, comments, and conversations): that beer itself isn’t political — that it only becomes political when someone decides to make it that way. That what we’re really seeing is a choice by individuals to inject division into something that doesn’t inherently require it. It’s a comforting idea. It’s also wrong — and I think it’s worth being precise about why. That framing assumes that breweries operate outside the conditions shaping everything else. That politics is something you choose to bring into a room that was, until then, clean and neutral. That if you stay quiet, you stay clear of it. But the room was never neutral. It was never clean. Politics is already in the room. It’s in who walks through the door comfortably and who hesitates. It’s in whether a space can be used for organizing without fear. It’s in whether helping someone quietly might carry consequences you have to think carefully about in advance. It’s in who staffed the brewery, who harvested the grain, who can afford to be a regular. The idea that you opt out of all that by staying quiet is an illusion. You only change how visible your response to it is. This is, I realize, a hard thing to hear if you came to a beer newsletter for something lighter. I wrote recently that “beer, for me, has always felt like a refuge — a third place in an increasingly fractured world.” I meant that. I still do. But a refuge is not an escape from reality. It’s a place to gather strength to face it. Here’s what I actually missed — and what I want to correct. Multiple people in the industry reached out to me. I’m not naming them and I’m not identifying their businesses, because that’s not my call. If and when they want to be loud about what they’re doing, that agency belongs to them. What I can share is the substance of what they said, because it complicated something I presented too cleanly. The overall message: *You don’t know what we all are doing.* And they’re right. I don’t. One example involved a collaboration brewed quietly to support another business facing serious challenges in a whole different region, with proceeds directed toward solidarity, community, and keeping operations afloat. No announcement. It could have been broadcast widely. The point was never publicity. Another example involved logistical support for community efforts: organizing safe transportation, providing space for meetings on otherwise closed days, facilitating gatherings under difficult conditions. All of it happening while balancing real financial pressure and genuine concern for personal safety. None of what they described is a brewer “deciding to make beer political.” It’s people responding to the conditions around them — conditions that are already shaping who feels safe, who has access, who can gather, who needs help, and who has the capacity to offer it. Politics, again, already in the room. Already shaping choices. Whether anyone announced it or not. I’ve spent decades in taprooms, at barrel releases, at festivals, in back offices and brewing floors, talking to the people who built this industry from nothing. I know how much happens that never makes it onto social media. I know the owner who quietly comp’d a tab for someone having a crisis. The brewer who drove an hour to pick up a stranger who needed a safe ride. The taproom that stayed dark on a Tuesday so a community group could use the space without it becoming A Whole Thing. None of that gets a post. Most of it never will. So when I wrote recently about silence — when I said that “silence right now doesn’t feel neutral, it feels like complicity” — I was writing about what I could see. And I was right about what I saw. The public silence of breweries that have the platform, the stability, and frankly the safety to say something and choose not to? That still troubles me. I’m not softening that. But some of what I read as silence is actually something else entirely. It’s people doing the work with their hands instead of their phones. It’s people who are genuinely afraid — not of being canceled, but of real consequences for their families, their employees, their ability to keep the doors open at all. That deserves more than a footnote. It deserves to be named clearly. Here’s the tension I want to sit with honestly: public statements matter. They matter because people can’t rally around something they can’t see. Visibility creates awareness and solidarity. It helps people find each other. It tells someone standing outside your taproom door, uncertain whether they’ll be welcomed inside, something they need to know — or whether it’s even safe for them to be in public at all. That’s not performative. I wrote recently that the craft beer movement “was built on collective defiance. It was built on rejecting consolidation. On pushing back against homogeneity.” I believe that too. And I’ll extend it: breweries should be at least as loud about their values as they are when they drop a new seasonal. Your hazy IPA gets a full rollout — the label art, the tap handle photo, the countdown post. Human dignity deserves the same energy. Be as loud about human rights as you are about your beer. There is no reason those two things should require different levels of courage from you. But visibility isn’t the only form of courage. And not everyone can be visible right now without real consequences — financial, personal, sometimes physical. There are people in this industry doing hard, unglamorous, sometimes risky work in the background, and announcing it would compromise it or paint a target on someone who’s already stretched thin. That’s not silence as complicity. That’s operational discipline under pressure. What I want to push back on — clearly, not gently — is the idea that behind-the-scenes action and public visibility are in competition with each other. The person organizing quietly in the back room and the person posting a statement of solidarity on a Tuesday morning are both doing something real. We need both. We need the quiet infrastructure and we need the visible signal. We need people to know that this industry — at its best, at its most independent, and human — gives a fuck. I closed that piece with a question: “Reactive and fearful? Or clear and values-driven?” That question still stands. But having heard from you, I’d add a corollary: the values-driven path isn’t always the loudest one. Sometimes it’s a phone call and a recipe. Sometimes it’s a room made available on a closed Tuesday. Sometimes it’s a drive across town for someone who needed a safe ride home. All of it is political. All of it was always political. You don’t get to opt out of that — you only get to decide what you do with it. I’ve spent more than a decade writing about this industry because I believe it can be exactly that. I’ve been lucky enough to build an audience that lets me say so plainly. That’s a privilege I intend to use. The work is happening. Some of it you’ll see. Some of it you won’t. Support it either way. Cleveland Prost is a reader-supported publication covering beer and brewing across New York state. To receive new posts and support this work, consider becoming a free or paid subscriber. Cleveland Prost is a reader-supported publication. To receive new posts and support my work, consider becoming a free or paid subscriber. Subscribe
🥐☕️FC Breakfast: Zlatan's shaved head, the UNFP blunder!
Zlatan’s shaved head ✂Zlatan Ibrahimović lost a bet with American football legend Tom Brady, who didn’t hesitate to follow through… clippers in hand.UNFP awards: another incomprehensible snub...
Science & Medicine: Weight loss surgery without the scalpel
Obesity rates in South Texas exceed the national average, but many patients hesitate to pursue bariatric surgery due to the risks involved. UT Health San Antonio now offers endoscopic alternatives that achieve comparable weight loss results with no incisions, shorter recovery times, and lower risk.
The State of Politics: Why UW President Candidates May Hesitate
The clumsy firing of Jay Rothman might discourage some top candidates.
Inside the sudden downfall of Eric Swalwell
As one California Democrat prepared to formally endorse Rep. Eric Swalwell for governor this spring, the lawmaker hesitated. They had heard rumors the married father of three slept around in Washington and worried about putting their name behind him in a crucial contest.
Losing Dexter Lawrence Would Make the Giants’ Defense Collapse
After years of contract issues, New York Giants superstar defensive tackle Dexter Lawrence II has requested a trade. Lawrence’s disgruntledness doesn’t come as a surprise. Despite his All-Pro production, he ranks just 12th among NFL interior defensive linemen in terms of salary. So, with Lawrence’s established, elite production at 28 years old, the Giants shouldn’t hesitate […] The post Losing Dexter Lawrence Would Make the Giants’ Defense Collapse appeared first on The Lead.
Exclusive: Worries over science, new addicts stymie US nicotine pouch fast-track scheme
Popular nicotine pouch products have yet to be cleared for sale in the United States despite a fast-track Food and Drug Administration scheme, as agency scientists hesitate to authorise them due to potential risks to new users, including children, three sources told Reuters.
Navigating the social media minefield
Scientists and researchers seeking to announce promising findings, exchange ideas or contribute to policy discussions outside of academic circles may find social media an expedient tool.But increasingly, scientists and other professionals are discovering that online platforms can be a double-edged sword: while sharing their work and expertise is crucial for visibility and meeting funder expectations, it also exposes them to baseless criticism and even accusations of spreading false information."It is getting harder and harder for scientists, and researchers in general, to convey their findings without facing attacks on their legitimacy and accuracy of their research," says Valère Ndior, a professor of public law at the University of Western Brittany in Brest, France, who has spent more than a decade studying misinformation on social media. Researchers attempting to challenge deceptive online information may themselves be accused of political bias or not being objective in their research, he explains, adding that some scientists disengage because they feel overwhelmed and unable to sustain meaningful dialogue. "It is quite sad to see in some instances that researchers end up leaving social media altogether because they feel like the pressure is getting too intense or feel threatened," he says.Ndior, a past president of the Francophone Network of International Law, is also involved in European efforts to make science and research findings more accessible to the public. As an ambassador for the Science Comes to Town (SCTT) project, he has participated in recent discussions on public perceptions of science and online misinformation. The European Commission-funded initiative connects Brest and two other cities — Kiel in Germany and Split in Croatia — and aims to strengthen ties between communities, universities and research institutions to promote science awareness and cooperation across Europe.Coordinated campaigns around contentious topicsNdior draws a clear distinction between critical thinking and thoughtless criticism. Yet he sees online discussions being increasingly shaped by suspicious behaviour and coordinated information campaigns — including "raids" aimed at dominating discussions and "astroturfing," where small groups act as larger movements to sway debates. Tracking these patterns has become harder because some platforms have restricted data or charge for it, despite provisions of the European Union's Digital Securities Act aimed at ensuring researchers can have access to such data. According to Ndior, "platforms became more reluctant from the moment access to data became a legal requirement rather than a voluntary initiative."Unfounded claims and scepticism about science existed long before Internet chat groups. But the noticeable rise in online hostility has intensified around contentious topics, such as the coronavirus pandemic and climate change, alongside the weakening of gatekeepers to moderate content.For Ndior, dubious claims about pandemic countermeasures and vaccine safety highlighted the struggle between "balancing freedom of expression and the protection of public health and order." Efforts to remove social media content deemed false or risky for public health triggered accusations of censorship and the silencing of legitimate discussion, and in some cases, legal challenges.Concerns about attacks on the credibility of scientists and researchers have generated a flurry of academic papers in recent years and prompted professional communities to address ways to counter online attacks. Such unease extends to the generation that has grown up with digital media. Ndior points out that his students, some of whom research artificial intelligence regulation, hate speech, online surveillance and other controversial topics, hesitate to share their work or viewpoints online. "Many of them don't want to expose themselves too much because they don't feel ready to be faced with the backlash of other people criticising their research," he explains.Safer harbours for engagementLegal challenges against false or defamatory posts are not necessarily a solution — especially given the trans-jurisdictional nature of the Internet. Lawsuits also take time and money, and if they fail, can be counterproductive. Instead, Ndior advises scientists and researchers to be selective in how and where they communicate. Professional online platforms and moderated discussion spaces offer a better environment for engagement. He also highlights the value of more traditional formats, such as radio interviews and in-person discussions at schools, libraries and science fairs, which encourage dialogue with the public. "Personal contact makes a big difference," he says, while acknowledging that these approaches lack the global reach of social media.Ndior’s interest in digital law and online misinformation stems from his time as a doctoral student in international law in the early days of social media. He began analysing posts from governments and heads of state to determine if they could be considered official and thus used as evidence in litigation. His work attracted media attention and led to conference and speaking invitations. "This was not part of my plan," he says, "but this is what happens as a researcher — your interest is sparked by a certain event or phenomenon, and it suddenly becomes your focus."Ndior believes SCTT provides "a double benefit" for researchers, enabling them to connect with peers and interact with the public. "There is a wide community of people who are not in academia who are critical thinkers looking for opportunities to ask questions, to get information and contribute their ideas,” he says. "I really value that kind of feedback."Science|Business, which connects policymakers, academics and industry through its news reporting, analysis and events, is an SCTT partner.
Navigating the social media minefield
Scientists and researchers seeking to announce promising findings, exchange ideas or contribute to policy discussions outside of academic circles may find social media an expedient tool.But increasingly, scientists and other professionals are discovering that online platforms can be a double-edged sword: while sharing their work and expertise is crucial for visibility and meeting funder expectations, it also exposes them to baseless criticism and even accusations of spreading false information."It is getting harder and harder for scientists, and researchers in general, to convey their findings without facing attacks on their legitimacy and accuracy of their research," says Valère Ndior, a professor of public law at the University of Western Brittany in Brest, France, who has spent more than a decade studying misinformation on social media. Researchers attempting to challenge deceptive online information may themselves be accused of political bias or not being objective in their research, he explains, adding that some scientists disengage because they feel overwhelmed and unable to sustain meaningful dialogue. "It is quite sad to see in some instances that researchers end up leaving social media altogether because they feel like the pressure is getting too intense or feel threatened," he says.Ndior, a past president of the Francophone Network of International Law, is also involved in European efforts to make science and research findings more accessible to the public. As an ambassador for the Science Comes to Town (SCTT) project, he has participated in recent discussions on public perceptions of science and online misinformation. The European Commission-funded initiative connects Brest and two other cities — Kiel in Germany and Split in Croatia — and aims to strengthen ties between communities, universities and research institutions to promote science awareness and cooperation across Europe.Coordinated campaigns around contentious topicsNdior draws a clear distinction between critical thinking and thoughtless criticism. Yet he sees online discussions being increasingly shaped by suspicious behaviour and coordinated information campaigns — including "raids" aimed at dominating discussions and "astroturfing," where small groups act as larger movements to sway debates. Tracking these patterns has become harder because some platforms have restricted data or charge for it, despite provisions of the European Union's Digital Securities Act aimed at ensuring researchers can have access to such data. According to Ndior, "platforms became more reluctant from the moment access to data became a legal requirement rather than a voluntary initiative."Unfounded claims and scepticism about science existed long before Internet chat groups. But the noticeable rise in online hostility has intensified around contentious topics, such as the coronavirus pandemic and climate change, alongside the weakening of gatekeepers to moderate content.For Ndior, dubious claims about pandemic countermeasures and vaccine safety highlighted the struggle between "balancing freedom of expression and the protection of public health and order." Efforts to remove social media content deemed false or risky for public health triggered accusations of censorship and the silencing of legitimate discussion, and in some cases, legal challenges.Concerns about attacks on the credibility of scientists and researchers have generated a flurry of academic papers in recent years and prompted professional communities to address ways to counter online attacks. Such unease extends to the generation that has grown up with digital media. Ndior points out that his students, some of whom research artificial intelligence regulation, hate speech, online surveillance and other controversial topics, hesitate to share their work or viewpoints online. "Many of them don't want to expose themselves too much because they don't feel ready to be faced with the backlash of other people criticising their research," he explains.Safer harbours for engagementLegal challenges against false or defamatory posts are not necessarily a solution — especially given the trans-jurisdictional nature of the Internet. Lawsuits also take time and money, and if they fail, can be counterproductive. Instead, Ndior advises scientists and researchers to be selective in how and where they communicate. Professional online platforms and moderated discussion spaces offer a better environment for engagement. He also highlights the value of more traditional formats, such as radio interviews and in-person discussions at schools, libraries and science fairs, which encourage dialogue with the public. "Personal contact makes a big difference," he says, while acknowledging that these approaches lack the global reach of social media.Ndior’s interest in digital law and online misinformation stems from his time as a doctoral student in international law in the early days of social media. He began analysing posts from governments and heads of state to determine if they could be considered official and thus used as evidence in litigation. His work attracted media attention and led to conference and speaking invitations. "This was not part of my plan," he says, "but this is what happens as a researcher — your interest is sparked by a certain event or phenomenon, and it suddenly becomes your focus."Ndior believes SCTT provides "a double benefit" for researchers, enabling them to connect with peers and interact with the public. "There is a wide community of people who are not in academia who are critical thinkers looking for opportunities to ask questions, to get information and contribute their ideas,” he says. "I really value that kind of feedback."Science|Business, which connects policymakers, academics and industry through its news reporting, analysis and events, is an SCTT partner.
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. 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