Markimrk

[SciTech Girl @scitechgirl]

🚨 ONE INJECTION COULD CHANGE OSTEOARTHRITIS FOREVER

What if damaged joints could repair themselves with just one injection?

Researchers at the University of Colorado Boulder are developing an experimental regenerative treatment designed to recruit the body’s own cells to rebuild damaged cartilage and bone.

In animal studies, a single injection delivered a regenerative drug gradually over several months. Treated joints showed major recovery within 4–8 weeks, with impressive regeneration even in severe injuries. Tests using human cells also showed promising regenerative effects.

But there’s a catch: this treatment has not yet been tested in human clinical trials. Researchers are now working through safety studies before moving toward human testing.

Source:
University of Colorado Boulder. (2026). Regenerative osteoarthritis treatment research. University of Colorado Boulder; Advanced Research Projects Agency for Health (ARPA-H), NITRO Program.

[Daniel Tawfik @dantawfik]

A specific strain of bacteria steadily disappears from your gut as you age. Researchers identified it, gave it to old mice, and reversed multiple hallmarks of aging across organs. A Nature Aging study reveals how this works.

Researchers at multiple Chinese institutions analyzed gut microbiome samples from hundreds of people across different age groups. They built a microbiome-based aging clock called MicroAge to track biological aging through bacterial composition.

One species kept appearing as depleted: Bifidobacterium pseudocatenulatum. The pattern held across both sexes and multiple independent cohorts. As people aged, levels of this bacteria consistently dropped.

Bifidobacteria are among the first colonizers of the infant gut. They dominate early in life, then decline over decades. The question was whether this decline contributes to aging or simply accompanies it.

The researchers tested this by giving B. pseudocatenulatum to naturally aged mice. The bacteria was administered orally as a monotherapy, meaning no other interventions, just this single bacterial strain.

The results showed improvements across multiple systems:

• Intestinal barrier function restored
• Inflammation reduced in gut, brain, liver, and muscle tissue
• Cognitive performance improved on memory tasks
• Motor coordination enhanced on physical tests
• Overall healthspan extended

Think of inflammation during aging, called inflammaging, as a slow fire burning across organ systems. It accelerates tissue deterioration, impairs function, and drives age-related disease. The probiotic treatment dampened this inflammatory state systemically, not just in the gut.

But probiotics work through the compounds they produce. The researchers identified the key metabolite responsible: 5-aminovaleric acid betaine, abbreviated as 5-AVAB.

This compound is produced by B. pseudocatenulatum during normal metabolism. When the researchers measured 5-AVAB levels in human samples, they found the same pattern as the bacteria itself. Levels declined with age.

To test whether 5-AVAB alone could produce the benefits, they supplemented aged mice with the pure metabolite, bypassing the bacteria entirely.

5-AVAB supplementation replicated much of what the probiotic did:

• Cognitive function improved
• Motor performance enhanced
• Inflammation suppressed across multiple organs
• Cellular senescence markers reduced

The metabolite worked without changing the gut microbiome composition. This distinguishes it from interventions that require microbial remodeling to function. 5-AVAB acts directly on host tissues.

The mechanism appears to involve suppression of inflammatory signaling pathways. Chronic low-grade inflammation is a central driver of functional decline during aging. Compounds that dampen this inflammation without broadly suppressing immune function could preserve healthspan.

This creates a framework for understanding why certain bacterial species matter during aging. It's not just about microbial diversity or total bacterial load. Specific species produce specific metabolites that directly influence aging processes in host tissues.

When those species decline, their metabolites disappear. The protective effects fade. Inflammation rises. Tissue function deteriorates. The aging trajectory accelerates.

The study doesn't answer whether supplementing B. pseudocatenulatum or 5-AVAB in humans would produce similar benefits. Mouse models of aging don't perfectly mirror human aging biology. The inflammatory profiles differ. The microbiome compositions differ. Translation requires human trials.

It also doesn't clarify optimal timing. Would supplementation work best when started in middle age as levels begin declining, or does it retain effectiveness even when begun late in life after substantial depletion has occurred?

The bacteria-metabolite axis identified here offers a testable target. B. pseudocatenulatum is already present in some probiotic formulations. 5-AVAB could potentially be synthesized and supplemented directly. Both approaches are technically feasible.

What the study establishes is a clear link between a specific depleting bacterial species, a declining metabolite, and measurable improvements in aging-related dysfunction across multiple organ systems. The mechanism operates through inflammaging suppression, one of the most consistent drivers of biological aging.

Whether this particular bacteria and metabolite become viable interventions in humans depends on trials that haven't happened yet. But the framework it provides for identifying microbiome-aging links through metabolite profiling applies beyond this single species.

[Grow Smarter @GrowSmarter_x]

Did you know ?

[Ashlee Vance @ashleevance]

The most influential longevity and aging investor is someone you likely have not heard of - Alex Colville.

Over the past decade, he's been dishing out millions to biotech starups, only doing so very quietly.

There is no more confusing field than longevity and aging. Celebrities, gurus, scientists will say just about anything to get you hyped and buying stuff.

Alex has long struck me as a different sort. He's been trying to find the real science that could affect lifespan. He reads the papers. He goes deep. He dodges a lot of the stuff others back.

This is our two-hour chat with Alex where gets into the technology that he thinks is real.

Thx, as always, to @brexHQ and @sendcutsend for making the Core Memory podcast possible. Get it on all major platforms and on our YouTube channel.

[Camus @newstart_2024]

David Sinclair takes daily Cialis for blood flow, aging, and a possible cancer edge.

On Modern Wisdom he says some ED drugs appear to flip the immune system from shielding certain tumors to attacking them. He also argues low circulation is a major, underappreciated driver of decline in muscle and brain.

A 2012 paper from his lab tied better blood flow to SIRT1. He takes a small morning dose hoping to delay dementia and keep hair follicles supplied. At that level he says there is no unexpected erection problem.

Useful discoveries sometimes hide in the last place anyone thought to look, including drugs first built for something else entirely.

[Rand @rand_longevity]

simulated human trials are coming

[Chubby♨️ @kimmonismus]

Crazy what we are witnessing: An experimental oral drug called TOFA made obese male mice lose 18% of their body weight in four weeks, mostly fat, without eating less or losing significant muscle.

It appears to increase energy expenditure by blocking new fat production while activating fat-burning pathways and worked even better alongside semaglutide or tirzepatide.

Literally dreams come true, fat losing pills are within reach. And you dont lose muscle. Study attached:

[Dr Singularity @Dr_Singularity]

Amazing

One of the most insane breakthroughs of this year so far

Scientists created an implant that mimics exercise, and fights aging.

Researchers built self contracting muscle grafts that continuously “exercise” inside the body. In mice, the implants increased muscle mass and strength, boosted bone density, reduced fat and inflammation, improved metabolism and even showed cognitive benefits while slowing several age related changes.

In the future, people will be able to eat whatever they want, never need to go to the gym, and still have bodies like Achilles. This is where we’re heading.

[Smart Science @SmartScience]

🎗 A brain tumor nearly vanished in just 5 days after one dose of a breakthrough treatment.

Experts say this may be the beginning of a cure.

In a landmark clinical trial at Massachusetts General Cancer Center, researchers have reported rapid and dramatic responses to a next-generation CAR-T cell therapy in patients with glioblastoma—one of the deadliest and most treatment-resistant brain cancers.
The personalized treatment reprograms a patient’s immune cells to attack the tumor, and in one extraordinary case, nearly eliminated the cancer within just five days. This novel therapy is designed to target multiple features of the tumor at once, a strategy that may help overcome the common challenge of treatment resistance in solid tumors like glioblastoma.

Although the tumors eventually returned, the early outcomes were described as unprecedented. One patient saw a 60% reduction in tumor size that lasted for half a year—an impressive result in a cancer known for its aggressiveness.

The trial’s success marks a major step forward for immunotherapy in brain cancer and raises new hopes for long-term control or even a cure. Researchers are now working to refine the treatment and extend its effects, with the ultimate goal of turning a once-terminal diagnosis into a survivable condition.

source
Source: Mass General Cancer Center. “A Major Milestone in Glioblastoma Research.”

[Daniel Tawfik @dantawfik]

Aging tissues become stiff. Heart, kidney, lung, and ovarian tissue all accumulate excess structural scaffolding that traps cells and blocks normal function. The process has been considered irreversible, part of the mechanical deterioration that defines aging.

A new study tested whether this could be reversed in aging ovaries. Researchers identified the inflammatory signal driving tissue stiffening and blocked it in mice and rats, restoring fertility that had already declined. The findings matter beyond reproduction because the same inflammatory signal drives stiffening across multiple aging organs.

That signal is interleukin-11, or IL-11, an inflammatory protein elevated across aging tissues. In ovaries, IL-11 activates fibroblasts to secrete extracellular matrix, the structural scaffolding surrounding cells. IL-11 levels rise in aging heart, kidney, lung, and liver tissue. All of these organs accumulate excessive extracellular matrix during aging. All of them stiffen in ways that impair function.

This study tested whether blocking IL-11 could reverse tissue stiffening in ovaries. The ovary served as the model system because age-related stiffness directly blocks follicle development, creating a clear functional readout.

Extracellular matrix isn't inherently problematic. Follicles need some matrix structure to develop properly. But when fibroblasts deposit too much matrix, the tissue becomes stiff. That stiffness creates a mechanical barrier that traps follicles and prevents them from growing, maturing, and ovulating.

Researchers used atomic force microscopy to measure ovarian tissue stiffness in human samples across different age groups and pathological conditions. The pattern was clear: ovaries nearly tripled in stiffness from the late twenties to early fifties.

Here's what they found:

• Young ovaries (18-28 years): 1.2 kPa average stiffness, AMH levels 3.9 ng/mL
• Middle-aged ovaries (35-42 years): 2.1 kPa, AMH 1.8 ng/mL
• Older ovaries (47-52 years): 3.4 kPa, AMH 0.6 ng/mL

The kPa measurements represent tissue stiffness, similar to how we measure blood pressure. AMH is anti-Müllerian hormone, the standard clinical marker for how many eggs remain. As ovaries became stiffer with age, the remaining egg supply dropped in parallel.

The stiffness pattern showed up in disease states too, not just normal aging. Women with PCOS, premature ovarian insufficiency from chemotherapy, or endometriosis all showed ovarian stiffness levels matching women decades older:

• PCOS ovaries: 3.2 kPa (comparable to 47-52 year olds)
• Chemotherapy-induced POI: 2.8 kPa
• Ovarian endometriosis: 2.9 kPa
• Age-matched healthy controls: 1.3 kPa

These conditions accelerate the mechanical aging process, producing the same tissue stiffness that normally takes decades to develop.

POI is premature ovarian insufficiency. All three conditions showed tissue stiffness comparable to ovaries decades older than the chronological age of the patients.

To identify what drives this stiffening, the team analyzed proteins in human ovarian tissue and gene expression in human ovarian fibroblasts. IL-11 emerged as a central regulator.

In aging ovaries, IL-11 expression was significantly elevated compared to younger tissue.

IL-11 works through a straightforward pathway. The protein binds to a receptor on fibroblast cells, which activates internal signaling that tells those cells to produce more collagen and other structural proteins. More structural proteins means stiffer tissue.

The researchers tested whether blocking this pathway could prevent the stiffening. They used three different methods in mice and rats: removing the IL-11 receptor genetically, using antibodies to block the receptor, and using RNA interference to silence IL-11 production directly.

All three approaches worked. In middle-aged mice with the IL-11 receptor removed, ovarian tissue stayed soft. At 10 months old (middle age for mice), these animals had tissue stiffness of 1.8 kPa compared to 3.2 kPa in normal aging mice. That's nearly half the stiffness of their age-matched counterparts.

Functional outcomes improved alongside the mechanical changes:

• IL-11 receptor knockout mice maintained higher follicle counts across all developmental stages (big deal)
• Primordial follicle reserve was preserved longer (another big deal)
• Ovulation rates remained higher in middle-aged knockout mice
• Fertility extended into later reproductive age

The team tested the same intervention in disease models. In chemotherapy-induced POI, blocking IL-11 signaling prevented the stiffness increase that normally follows chemotherapy treatment. Follicle counts and hormone levels remained closer to baseline compared to untreated controls.

PCOS affects about 10% of women of reproductive age. One of the defining features is irregular ovulation, where follicles either don't release eggs or do so unpredictably. The standard explanation focuses on hormonal imbalances, but this study suggests the mechanical environment plays a role too.

In PCOS mice, blocking IL-11 reduced ovarian stiffness and restored more regular ovulation patterns. The intervention worked at the level of tissue mechanics, not just hormone levels. When the tissue became less stiff, follicles could develop and release eggs more consistently.

Single-nucleus RNA sequencing revealed how blocking IL-11 changes the cellular composition of ovarian tissue.

In aging ovaries, a specific population of fibroblasts becomes hyperactive and expands over time. These cells produce excessive amounts of structural proteins and are locked in a state of continuous activation.

The activation is driven by the ERK pathway, one of the key signaling systems cells use to respond to growth signals and stress. When ERK is constantly active, it keeps telling fibroblasts to produce more matrix proteins. This creates the stiffening feedback loop that defines ovarian aging.

When IL-11 signaling was blocked, the proportion of activated fibroblasts decreased significantly. The fibroblast population shifted back toward a less activated state with lower matrix production. This explains the tissue-level stiffness reduction at the cellular level.

The most clinically relevant finding came from the therapeutic intervention experiments. Researchers treated already-aged mice and rats with nanoparticles carrying siRNA targeting IL-11. These nanoparticles were designed to accumulate specifically in ovarian tissue after systemic administration.

In 10-month-old mice treated with IL-11 siRNA nanoparticles for 8 weeks:

• Ovarian stiffness decreased from 3.2 kPa to 2.1 kPa
• Follicle counts increased across developmental stages
• Estrous cycles became more regular
• Fertility rates improved compared to age-matched untreated mice

The same treatment worked in aging rats. 12-month-old rats receiving IL-11 siRNA showed reduced ovarian stiffness, improved hormone profiles, and extended fertility compared to controls.

This matters because it demonstrates reversibility. The tissue stiffening that accumulates during aging isn't permanent structural damage. It's an active process maintained by ongoing IL-11 signaling. When that signal is removed, even in already-aged tissue, the mechanical environment can be restored.

The mechanism fits into the broader understanding of ovarian aging. Chronic inflammation increases with age in most tissues, a process called inflammaging. IL-11 is one component of that inflammatory environment.

Previous research has focused on IL-6 and TNF as drivers of age-related inflammation, but this study identifies IL-11 as specifically relevant to the mechanical aspects of ovarian aging.

The study provides mechanistic detail on how this happens. In follicles cultured in stiff environments, genes related to follicular growth were downregulated while inflammation and ECM reorganization genes were upregulated.

The mechanical signal creates a feedback loop where stiffness promotes more inflammation and more matrix deposition.

There are some really critical limitations of this mouse model study.

The human tissue measurements are correlational. Higher stiffness associated with aging and disease, but causality was established only in animal models. Whether blocking IL-11 in humans would produce similar functional improvements requires clinical testing.

The interventions were preventive or early therapeutic in the animal models. Mice and rats were treated before severe ovarian dysfunction developed or shortly after aging began. Whether the same approach works in late-stage ovarian insufficiency or after menopause isn't addressed by this data.

Safety and off-target effects need evaluation. IL-11 has roles in other tissues, including wound healing and inflammatory responses. Long-term suppression could have consequences beyond the ovary. The nanoparticle delivery system aims to concentrate the intervention in ovarian tissue, but complete specificity is unlikely.

Still, the therapeutic concept is supported by converging evidence. Surgical interventions that reduce ovarian stiffness, like ovarian fragmentation or drilling, have shown clinical efficacy in restoring fertility in some cases of POI and PCOS.

Those procedures work mechanically. An IL-11 antagonist would achieve the same mechanical outcome through a molecular intervention.

Clinical translation faces practical hurdles. The optimal dosing, delivery route, and treatment duration for IL-11 antagonism in human fertility applications haven't been determined.

Whether the treatment works for all causes of ovarian dysfunction or only those driven primarily by matrix stiffening is unknown.

What the study establishes clearly is that IL-11 is a druggable target that regulates tissue mechanics across aging. Matrix stiffness isn't a passive consequence of getting older, it's an active inflammatory process that can be modulated. Blocking one inflammatory protein is sufficient to preserve tissue mechanics and extend functional outcomes in multiple animal models.

The ovarian findings matter because they prove a concept that applies across tissues. IL-11 is elevated in aging heart, kidney, lung, and liver tissue. All of these organs accumulate excessive extracellular matrix during aging. All of them stiffen in ways that impair function. If the same IL-11 pathway drives mechanical aging across tissues, this represents a single intervention point that could address tissue stiffening systemically.

The convergence across aging, PCOS, POI, and endometriosis in ovaries suggests IL-11-driven stiffening may be a common pathway in multiple forms of tissue dysfunction. If confirmed in humans, this represents a mechanistic intervention that addresses a shared feature of age-related organ decline rather than treating each tissue separately.

Right now, we know IL-11 causes tissue stiffening that blocks normal function, and blocking it restores mechanical and functional outcomes in animal models. The ovary served as the proof of concept. Whether that translates to reversing tissue stiffness in other aging organs is the next question.

[BetterMe App @betterme]

Reach your muscle goals 💪
Stick to this simple plan to succeed:
1. Take a 1-minute quiz
2. Get a workout and meal plan
3. Follow the program (easy-peasy)

[𝕏 Travels, Hotels and Resorts @em3dia]

If you want to experience the true variety of the US, you need to drive through Arizona, Utah, and Colorado. Mapped out are the perfect 11-stop route that takes you from alien desert slot canyons to soaring alpine mountain peaks:

Stop 1: Page, Arizona; The ultimate desert hub. Home to the swirling sandstone walls of Antelope Canyon and the massive bend of Horseshoe Bend.

Stop 2: Zion National Park, Utah; Hike between towering 2,000-foot red sandstone monoliths and wade through the Virgin River in The Narrows.

Stop 3: Kanarra Falls, Utah; Squeeze through a hidden canyon to climb a rustic wooden ladder right next to a rushing waterfall.

Stop 4: Bryce Canyon, Utah; Stand at the rim to marvel at the world’s largest collection of crimson-colored rock "hoodoos."

Stop 5: Bentonite Hills, Utah; An otherworldly landscape that looks exactly like Mars, featuring rolling hills of technicolor, striped clay.

Stop 6: Canyonlands, Utah; Gaze out over a massive, rugged wilderness of deep canyons carved out by the Colorado River.

Stop 7: Monument Valley, Arizona; The classic heart of the American West, featuring giant, isolated red sandstone buttes towering over the highway.

Stop 8: Durango, Colorado; Cross into the Rockies! Board a historic 1880s coal-fired steam train through the wild Animas River gorge.

Stop 9: Million Dollar Highway, Colorado; One of the most breathtaking, thrilling drives in the world, snaking through sheer, guardrail-free mountain cliffs.

Stop 10: Ouray, Colorado; Nicknamed the "Switzerland of America," this historic mining town is nestled deep inside a jagged alpine bowl.

Stop 11: Breckenridge, Colorado; End your journey in a vibrant, high-altitude mountain village packed with historic charm and endless hiking trails.

🎥 ultimatevacationn | IG

[Smart Science @SmartScience]

Researchers at the University of Milan have identified that an enzyme called phospholipid transfer protein (PLTP) can effectively mobilize cholesterol from arterial plaques, sending it back into the bloodstream for natural disposal. This discovery is a potential game-changer because, unlike current treatments that primarily focus on preventing new plaque from forming, this method actually targets and dissolves existing blockages.

Atherosclerosis occurs when cholesterol and inflammatory cells create stable, hardened deposits in artery walls that resist traditional removal methods. When these plaques become too large, they severely restrict blood flow, often necessitating invasive procedures like stents or bypass surgery to prevent heart attacks or strokes.

The PLTP enzyme acts as a natural extraction system, pulling cholesterol out of the arterial wall and transferring it to HDL, or "good cholesterol," for transport to the liver. Scientists found that many people have naturally low levels of this activity due to genetic factors, which is why they have developed a gene therapy to boost PLTP expression directly where it is needed most.

In animal models, this localized boost in enzyme activity resulted in a 40% reduction in plaque volume in just three months, allowing narrowed arteries to reopen to nearly their original diameter. These results suggest that plaques not only become smaller but also more stable, which significantly lowers the risk of a sudden rupture that could cause a cardiac event.

While human clinical trials are currently focusing on patients with severe coronary artery disease who cannot undergo surgery, the long-term goal is a biological "reversal" of decades of arterial damage. If successful, this could shift cardiovascular medicine away from mechanical bypasses and toward a more natural, enzymatic cleaning of the circulatory system.

[Next Science @NextScience]

🚨 One Eye Drop Could One Day Replace Cataract Surgery

Scientists are testing a new eye drop called VP1-001 that may help clear cataracts without surgery. Instead of removing the cloudy lens, the drop works by repairing clumped proteins inside the eye helping light pass through normally again.

In early mouse studies:
61% of lenses regained better focus
46% became visibly clearer
Cataracts affect over 65 million people worldwide, making this discovery a potentially huge breakthrough for future vision care especially in places where surgery is difficult or expensive.

The treatment is still experimental, but researchers say it could change eye care forever.

Source:
Anglia Ruskin University. Researchers develop promising eye drop treatment for cataracts.

[David Sinclair @davidasinclair]

Rapamycin extends the lifespan of numerous species. A common “longevity” dose is 3 mg/once a week. New study reports a short-term rapamycin treatment (1 mg/d) improved immune & inflammatory markers, including reducing autoimmunity, but failed to reset the epigenetic clock

[SciTech Era @SciTechera]

reminder

Scientists just developed a 3-drug therapy that extended the lifespan of aged mice by 102.6 days 👀

"Researchers at UC Berkeley developed a three-drug combination called DMA using Dichloroacetate (DCA), Metformin, and low-dose Navitoclax (ABT-263)."

"This new therapy selectively eliminated senescent ("zombie") cells and cancer cells by exploiting their shared metabolic weakness while largely sparing healthy cells."

"In aged mice, DMA improved physical endurance, reduced age-related inflammatory markers, and extended remaining lifespan by 102.6 days (about 41.7%) using a 10-fold lower dose of Navitoclax, helping avoid its major platelet toxicity."

Study stage: Preclinical (cell and mouse studies only). Human clinical trials are still needed.

NOTE: Aging and cancer are the ultimate barriers to radical longevity.

[Aubrey de Grey @aubreydegrey]

New podcast, largely focused on Revel's breakthrough.

[David Sinclair @davidasinclair]

New episode of Lifespan: Inside the World’s First Age Reversal Trial. New updates on how the trial is going & how to maximize vision!
https://t.co/ChZb3EsOlz

[BetterMe App @betterme]

Reach your muscle goals 💪
Stick to this simple plan to succeed:
1. Take a 1-minute quiz
2. Get a workout and meal plan
3. Follow the program (easy-peasy)

[Avi Roy @agingroy]

We treat regeneration as a superpower that other animals, like salamanders, have and we don't. A 2025 study in @ScienceMagazine says it's still in us, just turned off.

Punch a hole in a rabbit's ear, and it grows back, skin and cartilage included. Do the same to a mouse, or to you, and the hole stays. A team in Beijing traced the difference to one gene, Aldh1a2, which makes retinoic acid, the signal that tells a wound to rebuild instead of scar. Rabbits turn it on at the injury. Mice carry the same gene, but evolution broke the switches that activate it.

So the team dropped one working rabbit switch into mice, and the mouse ears started closing their holes.

Mice, not people. But the program never left our genome. Evolution turned it off, and in a mouse you can turn it back on.