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6 Common Medications That May Decrease Dementia Risk
Some vaccines, along with heart medications and other drugs, appear to have a protective benefit.
Why Promising Cancer Drugs Failed: Scientists Uncover the Missing Piece
A new study helps explain why a promising class of cancer drugs has often failed to meet expectations in clinical trials.
Scientists discover natural hormone that reverses obesity
A hormone called FGF21 can reverse obesity in mice by activating a newly identified brain circuit tied to metabolism. Surprisingly, it works in the hindbrain—the same region targeted by GLP-1 drugs like Ozempic and Wegovy—but through a completely different mechanism. Instead of suppressing appetite, FGF21 ramps up the body’s energy burning. This insight could pave the way for more targeted weight-loss and liver disease treatments.
What is ‘Ozempic personality,’ and why does it make life feel ‘meh’?
Doctors and patients across social media are reporting a kind of emotional flattening while on GLP-1 drugs.
Drugmakers raised prices on hundreds of drugs despite Trump deals, Senate Democrats report finds
The findings raise questions about whether the administration’s “most favored nation” deals are having a meaningful impact on patients.
This CEO wants to cover weight loss drugs for employees. They're just too expensive.
As demand for GLP-1 drugs surges, employers and insurers are struggling to keep up with the cost. Some are dropping coverage altogether.
Analysis of Alzheimer’s Drugs Stirs Debate About Their Effectiveness
The review said a certain class of drugs had little clinical benefit, but many Alzheimer’s experts criticized the analysis, saying it unfairly lumped failed drugs with two recently approved treatments.
Common IBS medications linked to higher risk of death in major study
A massive, nearly 20-year study tracking over 650,000 Americans with irritable bowel syndrome is raising new questions about the long-term safety of common treatments. Researchers found that some widely used medications—including antidepressants and certain antidiarrheal drugs—were linked to a small but noticeable increase in the risk of death over time.
RFK Jr. promotes peptides. Now the FDA weighs easing limits on the unproven chemicals
A panel of outside advisers will review seven peptides at a meeting in July to determine if the unapproved drugs can be safely produced by pharmacies.
Cubans self-medicate as crisis takes toll on mental health: ‘There is no idea to hold on to’
Many people are turning to prescription drugs – and some to herbal remedies and even hard drugs – amid an outlook that feels bleaker than the collapse of the Soviet Union
Opinion | GLP-1 Experimentation Is Everywhere, and Science Can’t Keep Up
Millions of Americans are experimenting with the drugs. Science can’t keep up.
Opinion | GLP-1 Experimentation Is Everywhere, and Science Can’t Keep Up
Millions of Americans are experimenting with the drugs. Science can’t keep up.
Another US strike on suspected drug boat in the eastern Pacific kills 4
The U.S. military has launched a strike on another boat accused of carrying drugs in the eastern Pacific Ocean, killing four people | 830 WCCO
Some people don’t lose weight with GLP-1s. Evidence is building that the drugs are helping anyway
The majority of people who start taking GLP-1 medicines with the hope of losing weight, the drugs can quiet cravings and help them shed stubborn pounds. But research is also continuing to reveal GLP-1 medicines’ benefits independent of weight loss — even if people gain weight.
GLP-1 medicine improves liver health independent of weight loss, study finds
Researchers at Toronto's Sinai Health have found that semaglutide—the active ingredient in popular weight loss drugs that mimic the gut hormone GLP-1—acts directly on a subset of liver cells to improve ...
US states drop Medicaid coverage of GLP-1 weight-loss drugs as demand rises
Experts say any short-term financial benefit will be outweighed by long-term health costs related to obesity
Exclusive: GOP pushes sweetener for cash-pay drugs
Paying cash for drugs so far has limited appeal for insured patients.
The ‘Wild West’ of peptides is booming. Here’s what’s real, what’s risky and what’s next
In the early 2020s, interest in GLP-1 weight loss drugs exploded. Now, as we move deeper into the decade, a new buzzword is taking over: peptides.
Strikes on alleged drug boats kill 5, leave 1 survivor in eastern Pacific, US military says
The U.S. military says it blew up two boats accused of smuggling drugs in the eastern Pacific Ocean | KMBZ
Strikes on alleged drug boats kill 5, leave 1 survivor in eastern Pacific, US military says
The U.S. military says it blew up two boats accused of smuggling drugs in the eastern Pacific Ocean | 830 WCCO
Why Ozempic doesn’t work for everyone: Scientists just found a hidden reason
A new study reveals that popular diabetes and weight-loss drugs like Ozempic and Wegovy may not work as effectively for about 10% of people due to specific genetic variants. These individuals appear to have a puzzling condition called “GLP-1 resistance,” where their bodies produce higher levels of the hormone targeted by these drugs—but don’t respond to it properly.
Scientists Found a Common Brain 'Fingerprint' Across 5 Psychedelics
"This is a breakthrough in how we think about psychedelic drugs."
Scientists say we’ve been treating Alzheimer’s all wrong
Alzheimer’s isn’t just one problem—it’s a tangled mix of biology, aging, and overall health. That’s why drugs targeting a single factor have fallen short, even as new treatments show modest benefits. Scientists are now pushing toward multi-pronged strategies, from gene editing to brain-cell rejuvenation and gut health interventions. The goal: stop treating Alzheimer’s as one disease and start tackling it as a complex system.
Penn researchers use AI to surface unreported GLP-1 side effects in Reddit posts
Could mining Reddit with AI help spot drug side effects earlier? A new Penn study suggests it might. Using large language models to map patient posts to standardized medical terms, researchers analyzed more than 400,000 Reddit posts about GLP-1s and found both known side effects and possibly underrecognized symptoms, like menstrual changes. The team says the approach could eventually help generate early safety signals for other drugs and wellness trends discussed online.
Divorce boom may follow use of Ozempic and other GLP-1 drugs, experts warn
Research suggests GLP-1 drugs like Ozempic and Wegovy could double divorce risk, mirroring trends seen in bariatric surgery patients, experts say.
Hawaiʻi weighs shorter probation, lighter punishment for drugs
The proposed changes come after criminal justice stakeholders from across the state took an extensive look at the state’s penal code in a effort to address concerns and outdated practices
If you aren’t losing weight with GLP-1 drugs, this may be one reason why
Two genes involved in gut hormones that influence appetite and digestion may be a factor in how people respond to GLP-1 drugs, according to a new study.
'Ketamine Queen' to be sentenced for selling Matthew Perry drugs that killed him
Perry died at age 54 of an overdose of ketamine
'Ketamine Queen' to be sentenced for selling Matthew Perry drugs that killed him
Perry died at age 54 of an overdose of ketamine
'Ketamine Queen' to be sentenced for selling Matthew Perry the drugs that killed him
a e n prisons indictments general-news criminal-punishment courts u-s-news entertainment | Newsradio 1140 WRVA
'Ketamine Queen' to be sentenced for selling Matthew Perry the drugs that killed him
a e n prisons indictments general-news criminal-punishment courts u-s-news entertainment | KCBS All News 106.9FM and 740AM
'Ketamine Queen' to be sentenced for selling Matthew Perry the drugs that killed him
a e n prisons indictments general-news criminal-punishment courts u-s-news entertainment | KYW Newsradio
Scientists identify ‘neural fingerprint’ of psychedelic drugs in the brain
Analysis of more than 500 brain scans finds LSD, psilocybin and other psychedelics increase cross-talk between brain systems
To lower cholesterol, these patients got a one-time tweak to their genes
Doctors have never had so many cholesterol-lowering drugs at their disposal, but getting patients to take them every day is difficult. Gene-editing could open a new frontier.
Why the U.S. Spends So Much on Healthcare
A big reason is the high prices Americans pay for surgeries and drugs.
Study suggests GLP-1 drugs have mental health perks
The study doesn’t prove causality or determine why GLP-1s could be a boon to people with mental illnesses.
Album Review: 6WA by BigXthaPlug & 600 Entertainment
BigXthaPlug spent eight months in Nashville making a country-rap album that debuted at No. 7 on the Billboard 200, put “All the Way” with Bailey Zimmerman at No. 4 on the Hot 100, got him a Rolling Stone cover, and filled arenas with Jelly Roll. And then he came back to Dallas, rounded up four of his signees, and made a gangsta-rap record with N.W.A’s Straight Outta Compton on the cover. 6WA is the second group release from 600 Entertainment, named after the 600 block of Meadowridge Street in Ferris, Texas, where BigX and his people grew up. The whole thing is loaded with West Coast samples. From N.W.A.’s “8Ball,” Eazy-E’s “Real Muthaphuckkin G’s” and “Boyz-N-The-Hood,” Ice-T’s “6 in the Mornin’,” Snoop Dogg’s “Nuthin’ but a ‘G’ Thang” and more. BigX is staking his name on the lineup he built—Rosama, MurdaGang PB, Yung Hood, KevanGotBandz, KaineMusic—and claiming a lineage from 1,400 miles away while insisting Dallas is its own thing. A million dollars in cash, split and handed straight to his mother. That’s the first place BigX goes on “From the Bottom.” He’d probably still be in the streets if he didn’t have his son and daughter. He only started rapping to make life better for Carter. Couldn’t start his car back then, now people get starstruck at Starbucks, and he throws the whole field away in one sentence: “How you think we competin’? You on the same bag, I just made me some millions off country.” Goyard bags off a Nashville payday, and he wants you to know exactly how far he’s come from everybody else. “Safe to Say” does something similar but looser. It’s a straight Ice Cube “It Was a Good Day” flip, and BigX nails it. Wakes up, checks both phones, nobody’s locked up, kid accounts look good. Gets pulled over, only catches a warning. Pulls up on the squad to liquor, ladies, and haze. Rosama takes the second verse and matches him. Wakes up to his girl cleaning his cuticles, twins playing peekaboo, pays off his car, calls a cousin, sees the opps and they don’t trip. Lawyer calls, he beat his case. Rosama is the strongest voice in the 600 camp after BigX, and “Life of a Gangster” is why. Third person, riding low, blacked-out windows, snub-nose revolver. A character who chose sticking people up over selling dope. “Quick eraser like a number-two pencil.” He never breaks character, and his delivery drops lower and slower than anything he does on the group cuts, like he’s telling you something at a cookout that he probably shouldn’t. Then on “Long Live Fre$h” he’s a completely different rapper. “Short-bus diamonds, these bitches retarded,” wide-body Durango he can’t even park. That kind of range matters on a group record. MurdaGang PB’s best verse is on the title track. Feds at his door at 6 AM, cameras busted, flushing dope, ram truck putting everybody on the floor. Yung Hood on “The Hottest” just lays out four reasons to keep hustling. Who wants to be broke, women cost money, you need bail, and home has to be straight. It’s funnier and more honest than most rappers get when they’re trying to explain why they sell drugs. KevanGotBandz on “Ain’t Never Slowin’ Down” talks about his father getting caught on the dope while he’s sitting on $300K somewhere in the hills, which is a specific kind of guilt that doesn’t usually make it onto crew tapes. KaineMusic, the newest signee, takes the back half of “Who Dunnit” and introduces herself in third person—“Took flight just to show these hoes how to perform”—but it’s too short to know if she can hold a full song. The flex tracks fill the middle of the LP and mostly run together. “I Go” is Rosama and PB trading brands, guns, and food punchlines. Rosama’s “anemic, my iron tucked low in this shirt” is a slick gun bar, PB fires back with “.223 with a clip ‘bout as big as a toddler” and “I go Burger King, stay with that whopper.” Quick, funny sometimes, but it’s all shopping lists. “Dopeman” is a chant. “6ixer Party” brings Snoop Dogg, who does exactly what you’d expect Snoop Dogg to do. BigX contributes the night’s wildest overshare: “She say she brought a friend too, well, I’m tryna put sausage on her dental.” These songs move fast and don’t overstay, but three or four of them could trade verses and nobody would catch it. Midway through, The D.O.C. shows up for a spoken-word interlude. Tracy Curry. West Dallas native, former N.W.A affiliate, co-writer on a lot of the records getting sampled on this very album. He thanks BigX for the tribute and then gets direct: “This your time, this DFW time. You need to do it like we do it down here.” Leave bread crumbs so everybody behind you can eat. Keep God in your life. It’s fatherly and generous, and it does raise the question of whether 6WA follows that advice. The album borrows heavy. The cover art, the Eazy-E samples, “Amerikkka’s Most Wanted” opening with a direct “Boyz-N-The-Hood” lift, Yung Hood rapping “Flag on my left side, Crip until I die.” But the stuff that actually stays with you is Dallas. BigX talking about Pleasant Grove, Rosama calling himself a country boy, PB recounting a raid that could’ve been last Tuesday. The record smells most like itself when it smells like Ferris, Texas, and least like Compton. BigX on “The Hottest” says his father was the first person he knew who had chickens. Not the way rappers usually wave at the drug trade. He means his actual father, his actual family. On “600 Degrees,” Rosama compares his chopper’s stutter to a speech disorder, PB claims he still has the block on his back even after leaving the city. BigX closes that one saying he used to spin and smack, and now the plaques are platinum. Thirty-two minutes was right for this. Nobody overstays, Tony Coles and Rance and Charley Cooks keep the production punchy, and BigX gives his signees real room instead of crowding every song. 6WA doesn’t reinvent anything. Five rappers, good beats, short clock. Most of what they say you’ve heard before. Some of it—the million to his mother, the cuticles and peekaboo, the four reasons to hustle—you won’t forget. Solid (★★★½☆) Favorite Track(s): “Safe to Say,” “From the Bottom,” “The Hottest” Subscribe
EPA puts microplastics, drugs on tap water list
A $144 million study into microplastics in water was also announced
Hims & Hers Health, Regeneron, Biogen, BioMarin Pharmaceutical, and Moderna Shares Are Falling, What You Need To Know
A number of stocks fell in the afternoon session after reports revealed that the US may impose up to 100% tariffs on imports of branded and patented drugs.
Trump expected to impose new tariffs on certain pharmaceutical drugs
President Donald Trump plans to impose new tariffs on pharmaceutical companies that have not struck deals to sell their drugs directly to consumers as part of his “Most Favored Nation” pricing initiative, according to a draft of an order obtained by CNN.
How the Internet Became the ‘Cookbook’ of the Drug Trade
A baffling overdose death took investigators to the frontier of ultra-potent synthetic drugs. The clues were hauntingly familiar.
Butterfat, Bots, and Bureaucrats: The Limits of Optimization
Across various fields, we constantly attempt to refine, control, and optimize complex systems. But whether it’s chatbots reshaping beliefs, cows engineered for more nutritious milk, drugs that suppress desire, or regulators chasing vanishingly small risks, each effort reveals the same tension: control involves tradeoffs. The issue isn’t whether optimization works—it’s what it costs and whether we notice it in time.
The Guardian view on peptides: Robert F Kennedy Jr would leave public health policy to the hucksters
Editorial: The US health secretary says he is a big fan of peptides. Many are promising drugs, but the only way to know their utility is proper clinical trials
Psychedelic therapies are becoming mainstream. Deutsche Bank thinks this drug developer could triple
This biopharma play with two key drugs for treatment-resistant depression could see its stock rise by more than 230%, according to a Deutsche Bank analyst.
Can We Ask Our Son to Go on Weight-Loss Drugs in Exchange for a House?
My husband wants to condition the gift on our son’s getting on a GLP-1 program. I feel that a gift is a gift and you should not extort a grown man.
Vanderbilt Lung Transplant Program sets new record
The Vanderbilt Transplant Center is now the second largest lung transplant center in the United States by volume, with 149 lung transplants in 2025, the most ever in one year at Vanderbilt Health. The Vanderbilt Lung Transplant Program leads the nation in organ preservation and regeneration and is among the best in long-term outcomes, demonstrating the success of the interdisciplinary team in caring for these complex patients. Several features make the program unique in the United States, said Konrad Hoetzenecker, MD, PhD, professor of Thoracic Surgery and surgical director of the Vanderbilt Lung Transplant Program. Vanderbilt serves as a “second opinion center” and accepts most complex candidates that are turned down by other centers due to increased perioperative risk. This includes patients over 70 years old, patients requiring combined procedures with their transplant, multiorgan transplantations and sensitized patients (individuals who have pre-formed anti-HLA antibodies who are at higher risk for complications). The expertise and excellent outcomes have attracted patients far beyond the borders of Tennessee; almost half of Vanderbilt Health’s lung transplant recipients come from out of state. “Another unique feature is our minimally invasive transplant program,” Hoetzenecker said. “By using distinct surgical instruments and techniques, the incisions can be kept as small as 7 to 8 centimeters, which results in better healing, less pain and faster recovery. “This minimally invasive approach is embedded in an Enhanced Recovery After Surgery (ERAS) protocol, a multimodal, evidence-based perioperative care pathway designed to reduce surgical stress, minimize complications and speed up recovery. Our unique ERAS protocol, by a dedicated interdisciplinary approach, aims to improve recovery after lung transplant and reduce ICU and hospital stay.” The lung transplant program recently celebrated a milestone — 1,000 lung transplants since the program began in 1990. “This significant achievement reflects the concerted effort of a multidisciplinary collaboration by the Departments of Thoracic Surgery, Medicine, Anesthesiology and Critical Care,” said David Erasmus, MD, associate professor of Medicine and medical director of Vanderbilt Lung Transplant. Lung transplants have been attempted since the 1960s, but they were largely unsuccessful until the 1980s, when surgical techniques were refined and new antirejection drugs proved effective. Patient outcomes steadily improved from the 1990s to the present. Vanderbilt’s fourth lung transplant recipient in 1990, Pam Everett, is the longest-living, single-lung transplant known in the world, recently celebrating 35 years since her transplant. The Vanderbilt Lung Transplant surgical team is led by Hoetzenecker and Caitlin Demarest, MD, PhD, the surgical director and associate surgical director of the Vanderbilt Lung Transplant program. Erasmus is the medical director of Vanderbilt Lung Transplant along with Anil Trindade, MD, associate medical director and associate professor of Medicine.
Scientists discover why cancer drugs don’t work for everyone
Scientists have uncovered a hidden reason why cancer treatments don’t work equally well for everyone. Certain drugs can become trapped inside lysosomes within tumor cells, forming slow-release reservoirs that create uneven drug distribution. This means some cancer cells are heavily exposed while others are barely affected. Understanding this process could help doctors better tailor treatments and improve outcomes.
13 surprising ways GLP-1s may benefit the body, according to science
A condition-by-condition guide to GLP-1 drugs breaks down what’s proven, promising and still untested.
How to Turn a Chicken Egg Into a Drug Factory
A biotech start-up is testing a novel way of efficiently producing pharmaceutical drugs.
The brain's cleaning system can be boosted to rid Alzheimer's proteins
A duo of drugs that boosts our glympathic system, which clears waste from our brain, also improves the removal of proteins associated with the onset of Alzheimer's disease
Julio Fuentes: Florida amends SB 1760 to protect access to lower-cost drugs
Lawmakers preserve competition to keep prescription drugs affordable for Floridians
Stopping GLP-1 drugs like Ozempic erodes heart health benefits quickly, new study finds
Stopping GLP-1 drugs like Ozempic quickly erodes heart protection, with two years off the medication raising cardiovascular risk by 22%, a new study finds.
Demand for GLP-1 pills and shots surges, and not just for weight loss
Use of blockbuster anti-obesity drugs like Wegovy and Zepbound is growing, with about 1 in 8 adults in the U.S. saying they currently take the medications.
As demand for GLP-1 pills and shots surges, healthy habits are still key
Whether they’re using weekly shots or daily pills, more Americans than ever are turning to anti-obesity drugs to lose weight and boost health.
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.
Inside a rare lab that's blazing a bold trail as it hunts for new drugs
A scientist from Zambia who loves — LOVES! — chemistry runs a lab in South Africa that is being hailed for "extraordinary" work.
Inside a rare lab that's blazing a bold trail as it hunts for new drugs
A scientist from Zambia who loves — LOVES! — chemistry runs a lab in South Africa that is being hailed for "extraordinary" work.
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Assessing Suzhou Ribo Life Science’s Valuation After Recent Share Price Weakness
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