Lifespan Research Institute Launches Public Longevity Group

Date Posted: September 17, 2025

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Lifespan Research Institute Launches Public Longevity Group

[Mountain View, September 17, 2025] — Lifespan Research Institute (LRI) today announced the launch of the Public Longevity Group (PLG), a new initiative focused on bridging the cultural gap between scientific breakthroughs in aging and their public acceptance. To kickstart its work, PLG has opened a crowdfunding campaign to develop tools that measure and strengthen public trust in longevity science.

While the science of longevity biotechnology continues to advance, skepticism and cultural resistance limit progress, with some studies showing that more than half of Americans would reject a safe, proven therapy to extend life. This hesitation poses risks of raising costs, delaying health-promoting regulation, and slowing the delivery of treatments that could combat age-related diseases and extend healthy lifespan.

“The breakthrough that unlocks all other breakthroughs is public trust,” said Sho Joseph Ozaki Tan, Founder of PLG. “Without it, even the most promising therapies may never reach the people they’re meant to help. PLG exists to change that.”

“Persuasion is a science too,” said Keith Comito, CEO of Lifespan Research Institute. “To bring health-extending technologies to the public as quickly as possible, we must approach advocacy with the same rigor as our research. With PLG, we’ll be able to systematically measure and increase social receptivity, making the public’s appetite for credible longevity therapies unmistakable to policymakers, investors, and the public itself.”

PLG is developing the first data-driven cultural intelligence system for longevity—a platform designed to track real-time sentiment, test narratives, and identify which messages resonate and which backfire. Early tools include:

The Longevity Cultural Clock: a cultural barometer mapping readiness and resistance across demographics and regions.
Sentiment Dashboards: real-time monitoring of public, investor, and policymaker perceptions.
Narrative Testing Tools: data-driven analysis that will enable robust pathways to public support.

The crowdfunding campaign will provide the initial $100,000 needed to launch these tools, creating the cultural foundation required for healthier, longer lives.

With a lean, data-driven team, the group aims to provide open-access cultural insights for advocates and policymakers while offering advanced analytics to mission-aligned partners.

Campaign Timeline:

Campaign completion: November 2, 2025
Dashboard development: Dec 2025 – Feb 2026
First survey deployment: Feb – Apr 2026
Beta dashboard launch: May 2026
First public insight report: June 2026

Supporters can contribute directly at: https://lifespan.io/campaigns/public-longevity-group/

The PLG campaign is sponsored by the members of LRI’s Lifespan Alliance, a consortium of mission-aligned organizations that believe in the promise of extending healthy human lifespan. Newly-joined members include OpenCures, AgelessRx, and Lento Bio.

About Lifespan Research Institute

Lifespan Research Institute accelerates the science and systems needed for longer, healthier lives by uniting researchers, investors, and the public to drive lasting impact. LRI advances breakthrough science, builds high-impact ecosystems, and connects the global longevity community.

Media Contact:

Christie Sacco

Marketing Director

Lifespan Research Institute

christie.sacco@lifespan.io

(650) 336-1780

We would like to ask you a small favor. We are a non-profit foundation, and unlike some other organizations, we have no shareholders and no products to sell you. All our news and educational content is free for everyone to read, but it does mean that we rely on the help of people like you. Every contribution, no matter if it’s big or small, supports independent ethical journalism and sustains our future.

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Date Posted: August 3, 2026

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Rejuvenation Roundup July 2026

The fight for longevity treatments that measurably improve and lengthen quality of life is ongoing in research, treatment, and policy, with promising successes and a horrifying failure. Here’s what’s happened in July.

Interviews

Gabriel Cian on Building the 2060 Longevity Ecosystem: In this follow-up interview, we speak with Gabriel Cian about how the 2060 ecosystem has evolved since last year’s Forum, what he learned from the first edition, and how he is thinking about investment, scientific credibility, health optimization, policy, and the future of longevity in Europe.

José Pedro Castro on Inflammation and Aging: We discussed the idea that inflammation underlies both important functions and many processes of aging, and how future therapies might help us keep up this elusive youthful inflammatory profile.

Advocacy and Analysis

Optimizing Guidelines Toward Optimal Health Outcomes: In a recently published perspective paper, the author argues that the UK’s official health guidelines on physical activity and protein intake should be revised to recommend levels necessary to achieve optimal health, rather than the bare minimum currently recommended.

NYC Woman Dead After Receiving a “Longevity Infusion”: According to the experts that we spoke to, the death, which followed an intravenous NAD⁺ infusion that went catastrophically wrong, underscores the risks of unproven treatments and the need for rigorous longevity medicine.

Montana’s Right-to-Try Law Enters a New Phase: Montana’s first experimental treatment review board has brought three longevity heavyweights into the state’s effort to expand access to experimental therapies.

Research Roundup

Intermittent Fasting Increases Lifespan in Male Mice: Restricting food access to an 8-hour window increased median lifespan in male mice by 12%. However, that might be due to voluntary caloric restriction induced by the regimen.

How Muscle Loss and Bone Loss Are Related: Researchers have elucidated some of the links between the age-related loss of muscle (sarcopenia) and the age-related loss of bone (osteoporosis).

Rescuing Calcium Ion Homeostasis Extends Mouse Lifespan: Scientists have linked disrupted Ca²⁺ homeostasis to aging in both progeroid and naturally aging mice. Rescuing it with a well-known antidepressant significantly increased the animals’ median and maximum lifespan.

An Experimental Proposal for Blocking Ambient Radiation: A perspective published in Aging and Disease has recommended the use of underground laboratory space in order to remove the effects of surface radiation on biological clocks.

Combining Senolytics and Stem Cells Shows Promise in Mice: A new study associated with Immorta Bio suggests that combining a senolytic vaccine with mesenchymal stem cells might create a synergistic impact. However, the findings rest on acute, artificially induced injury models rather than natural aging.

Peripheral Inflammation May Drive Parkinson’s: A new study suggests that aging or Parkinson’s-triggering mutations create inflammation in peripheral tissues, and then circulating extracellular vesicles spread it to the brain, which might contribute to the disease.

Activating a Key Receptor Fights Thymic Involution in Mice: Publishing in Aging Cell, researchers have devised a way to delay the aging of the thymus by targeting GPR40, a key receptor in its epithelial cells.

Engineered Enzyme Reverses Age-Related Protein Damage: Scientists have engineered an enzyme that removes an advanced glycation end product (AGE) from proteins. This type of age-related modification, which affects protein function and can trigger inflammation, has previously been considered extremely hard to reverse.

Exosomes From Stem Cells Fight Liver Disease in Mice: Researchers have described a method of using exosomes derived from mesenchymal stem cells (MSCs) to fight harmful metabolic changes in the liver.

Regular Training Erases Parts of Muscle Aging Signature: A new study suggests that regular planned exercise, not just being generally active, protects against certain aspects of muscle aging.

The Progress and Future of Biological Aging Clocks: A recent review discusses the development of biological aging clocks, their capabilities and limitations, the discoveries they enabled, and possible future developments in this area.

More Autophagy Reduces Toxin-Induced Kidney Failure in Mice: Autophagy, which increases in younger mice under toxic stress, does not increase in older mice and leaves them susceptible to acute kidney injury (AKI).

How the Immune System Makes Sun Damage Worse: In Aging Cell, researchers have published an explanation of how neutrophil extracellular traps (NETs) worsen UVB damage and how inhibiting them alleviated this damage in a mouse model.

Short-Term Stresses May Undermine Clock Results: A team of researchers has concluded that while methylation-based epigenetic clocks generally give reliable outputs when given the same inputs, short-term biological fluctuations can drastically change their results.

Lifelong restriction of dietary valine has sex-specific benefits for health and lifespan in mice: This paper has found that it improves multiple aspects of healthspan in mice of both sexes, extends lifespan in male mice, and suggests that interventions that mimic it may have translational potential for aging and age-related diseases.

Early-life sugar rationing, brain aging, and long-term neurodegenerative and psychiatric health outcomes: a population-based natural experiment study: These quasi-experimental findings suggest that early-life sugar restriction is associated with attenuated neurobiological aging and lower risks of dementia and psychiatric disorders.

Enhancing the Anti-Aging Capacity of hUC-MSCs via NMN Co-Treatment in D-Galactose-Induced Mice and Cellular Senescence Models: Taken together, this study provides a promising combinatorial approach that sustains stem cell function and amplifies anti-aging efficacy.

Young cardiac telocyte-derived exosomes rejuvenate aging hearts in rats: Y-CT-exos rejuvenated cardiac aging through multiple avenues, including ameliorating the senescence of cardiomyocytes and cardiac fibroblasts.

Engineered Red Blood Cell-Derived Extracellular Vesicles With Klotho Peptide Protect the Kidney From Fibrosis: Collectively, these findings demonstrate that klotho-engineered EVs effectively inhibit TGFβ-driven fibrosis and preserve tubular integrity, highlighting a promising therapeutic strategy for targeting kidney fibrosis.

Intermittent chloroquine treatment extends lifespan and prevents mammary hyperplasia in female rats while reducing serum ldl and igfbp3 levels: These findings indicate that this treatment is associated with extended lifespan and coordinated physiological adaptations in aged rats.

Prebiotic and postbiotic synergy alleviates age-related dysbiosis and inflammation in mice: Combining prebiotics and postbiotics modulates immune responses in aged mice, restoring adult-like levels through gut microbiota changes.

Selective targeting of cancer and senescence via shared metabolic shifts extends lifespan of old mice: While the in vivo effects of DMA are yet to be fully explored, these findings suggest that it might represent a new, clinically viable way to combat cancer and senescence without toxicity to healthy cells and tissues.

Biological limits of lifespan extension: Evidence for a shift from pathway leverage to system-level buffering across species: In simple organisms, aging is governed by a limited number of high-leverage pathways, whereas in mammals it emerges from distributed, multi-tissue regulatory systems characterized by redundancy, feedback, and competing physiological constraints.

News Nuggets

Forever Healthy Launches Evipedia AI Integration: Forever Healthy has announced the launch of a set of new tools to make it easier than ever for AI agents, research pipelines, and AI environments to integrate Evipedia.

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Date Posted: July 31, 2026

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José Pedro Castro on Inflammation and Aging

For the last several years, Dr. José Pedro Castro, a Gladyshev Lab alumnus, who is now Assistant Researcher and Project Principal Investigator at the Institute for Research and Innovation in Health at the University of Porto, has been studying inflammation and its crucial role in aging and disease. Earlier this month, he received the Rising Star Award at Longevity Summit Dublin.

At the summit, Dr. Castro presented his yet unpublished concept of “inflammatory fidelity”: maintaining a healthy, balanced inflammatory homeostasis, which gets disrupted with age. We discussed the idea that inflammation underlies both important functions and many processes of aging, and how future therapies might help us keep up this elusive youthful inflammatory profile.

What is your personal story of getting into the longevity field?

Unfortunately, I don’t have one of those amazing stories about why I joined the longevity field. I finished my degree in microbiology and then started a master’s project using blood from centenarians. We were looking for oxidative changes in proteins and asking whether those proteins were better preserved than in controls.

That’s how I got excited about aging. It’s one of those fields where you start working on one thing and suddenly find yourself in a completely different system. During my master’s, I began with T cells and immunosenescence. At the time, we knew much less about it, and most of the discussion was about oxidative stress and redox biology.

From there, I moved into muscle and adipose tissue and started seeing how closely those tissues are connected. I also began to think that oxidative stress alone couldn’t explain aging. I finished my master’s, did a Ph.D. on T-cell aging and protein aggregation, and then joined Tilman Grune’s group in Germany for my postdoc. We looked more and more at metabolism and aging – for example, how oxidative stress might mimic aging in fat or muscle.

Near the end of that postdoc, I became interested in Vadim Gladyshev’s lab. I read his paper introducing the “deleteriome,” the buildup of many different harmful changes with age. I couldn’t sleep for almost two days after reading it. I kept thinking: aging isn’t just oxidative stress or DNA damage. It’s a combination of many things, including some we may not even know about.

Vadim was taking a systems approach, which was new to me: everything is connected. There may be important hubs, of course, but no single pathway explains the whole process. I wrote to him with ideas for experiments, we connected, I got a grant from Germany, and I joined his lab. Suddenly, I was working across many systems – gene expression, DNA methylation, different tissues, different species.

That completely shifted my interests. If you want to understand aging, you need tools like multi-omics that show how the whole system changes, not just one protein or pathway. So my journey was from one protein and one model to trying to look at as many connected processes as possible. It’s difficult, but it gives you a much better sense of how complex aging really is.

Does that immense complexity ever frustrate you? Do you think we will understand enough to start reversing aging in the foreseeable future?

I don’t know whether we’ll reverse aging completely, because there are so many things we don’t even know to look for, but I think we can slow it meaningfully and perhaps reverse some parts of it.

What’s both exciting and exhausting is that an amazing paper now comes out almost every day, often with powerful new tools and huge datasets. You want to use everything. You see a result and immediately wonder how your model fits into it, but then it becomes very hard to coordinate all of that and still tell a clear story or make a specific contribution.

That’s one reason I decided to focus more narrowly on inflammation. Once I really started digging into inflammation and biological age, I found that despite the enormous literature, some important questions had barely been studied.

Inflammation has been studied for decades and is recognized as a hallmark of aging. At the same time, there is a growing sense that its role may be even broader – that it underlies many aging processes and could be one of the most universal targets for longevity therapies. How should we think about inflammation in aging today?

The term “inflammaging” did something very important: it made people aware that chronic inflammation probably contributes to aging and underlies many chronic diseases. But, there’s a bias. If you search for harmful inflammation and disease, the number of papers has risen almost exponentially. Research on adaptive, regenerative, or otherwise helpful inflammation has stayed much flatter.

Basically, people have focused almost entirely on the bad side, but we need inflammation to fight infections and repair tissues. I think we’ve overlooked that side of it.

That led us to a concept we call “inflammatory fidelity,” which I discussed in Dublin. We need to find inflammatory circuits linked to aging and accelerated biological age, but also different circuits linked to development, adaptation, and regeneration.

Embryos regenerate very quickly. The neonatal heart can still regenerate too, but it loses that ability soon after birth, and inflammation is involved. Using transcriptomic data from embryonic development through late life, we found two broad inflammatory circuits. One is very active during development and early life and then drops sharply. The other starts low and rises with age.

We combine their expression into a fidelity score – very simply, beneficial inflammation divided by harmful inflammation. The score falls in aging, chronic disease, and fibrosis. It rises in regeneration and in signatures linked to longer lifespan.

So, the score seems to track the state of a cell or organism. It could add something to biological-age measures, which may or may not capture inflammation. If you were running a clinical trial, for example, it might not be enough to measure IL-6 or C-reactive protein. Someone could have high pro-inflammatory markers but still have strong regenerative or adaptive pathways that buffer the damage.

Centenarians are a good example. Some studies find high IL-6 and other inflammatory markers in centenarians, yet they stay resilient until very late in life. That suggests they have compensatory mechanisms.

Context matters enormously too. When we activate one of the inflammatory circuits we found, the effect changes with age. In a middle-aged mouse, we see harmful cytokines, inflammatory macrophages, and changes in the immune system, but the mouse can still produce many regulatory T cells that try to hold the response back.

So the question isn’t simply whether inflammation is there. When did it start? What’s the context? IL-6, for example, can be pro-inflammatory in one setting and support regeneration in another.

Or when IL-6 rises acutely in response to exercise, right?

Yes, exactly. In the liver, for example, macrophages need to secrete IL-6 to promote regeneration. The outcome depends on timing, dose, the cell type, and the combination of signals.

Tell me if I understand this correctly: inflammatory fidelity is something like maintaining a healthy inflammatory homeostasis. We have a youthful blueprint in which the system is balanced, and with age, the harmful side begins to dominate. The idea is to bring it back to that more youthful state.

Exactly. That’s the next step for us. We now have candidate transcription factors that seem to control these circuits. We want to test them in different cell types: boost the factor controlling beneficial inflammation, reduce the one controlling harmful inflammation, and see which age-related features improve.

Take macrophages. Young macrophages can help the heart regenerate, while old macrophages promote fibrosis and damage. Can we restore inflammatory fidelity in old macrophages? If we reprogram them for cell therapy, or change them directly in vivo, can we improve regeneration after injury in the heart, liver, or other tissues? And would aging clocks show a younger state? We don’t know yet.

Another big gap is causality. We know inflammation tracks with aging and disease. We give rapamycin, and IL-6 falls; we try another intervention, and some marker goes up or down. But which inflammatory pathways actually make biological age move faster or slower?

In a separate project, we used transcriptomic clocks and their inflammatory modules to predict genes linked to accelerated transcriptomic aging. We chose the strongest, most consistent candidate across datasets such as Tabula Muris Senis. When we treated cells with an agonist for the receptor we found, their transcriptome shifted toward an older state. We’re also testing it in mice.

The main point is that it’s not enough to say inflammation rises with age or falls after a geroprotective treatment. We need to find the specific circuits that actually push biological age up or down.

The inflammatory-fidelity work is still unpublished, but you recently posted a preprint on an inflammation-based epigenetic clock. Tell me more about it.

The fidelity project came later and is still at an early stage. We have a lot of in silico evidence, but we’re only starting the lab validation.

The clock project came from that inflammatory circuit linked to accelerated transcriptomic age. We had a set of genes connected to that state. I contacted Csaba Kerepesi, a former member of Vadim’s lab and a friend, and we asked: if this signature is tied to transcriptomic aging and is strongly enriched for inflammation, can we use it to build an epigenetic clock?

Most epigenetic clocks are black boxes. They can predict very well, but you often don’t know what biology the selected CpG sites represent. Is it inflammation, DNA repair, or something else?

So, you went the opposite way – from the functionality.

Exactly. We started from the biology. We already had a little over 100 inflammation-related genes with a clear function. We knew this group of genes was heavily enriched for inflammation. So we thought: if it really captures inflammation, perhaps a clock built from these genes should pick up diseases in which inflammation plays a major role.

We selected CpG sites in the promoters of those genes and built the clock. It tracks epigenetic age and age acceleration in several chronic conditions, including immune and cardiovascular disorders and many cancers. One interesting analysis compared normal tissue, tissue next to a tumor, and the tumor itself. The predicted age rose from normal to adjacent tissue and then rose again in the tumor.

We also asked whether it could pick up rejuvenation. In OSKM partial-reprogramming data, the predicted biological age went down. To me, that was exciting. We wanted to show that if you start with a meaningful pathway linked to accelerated aging, you can build a clock that still detects age acceleration and deceleration.

OSKM validation is really interesting, but on the other hand it’s all epigenetic reprogramming. You could argue that the factors do something to the epigenome, including somehow recalibrating those genes – and that’s what you see in the readout.

Yes. That doesn’t prove inflammation itself was rejuvenated. OSKM directly remodels the epigenome, so it may simply be changing those promoters, but at least it suggests that this inflammation-related signal is involved.

Have you looked then at other validations, other therapies?

We want to. That work is underway. We’d like to test rapamycin and whatever other intervention datasets are available.

Did you test your inflammation-based clock against more established epigenetic clocks?

Yes. We compared it with established clocks, including Horvath, Hannum, GrimAge, and GrimAge2. They don’t agree perfectly in every dataset, but overall we saw similar trends. That mattered because our clock didn’t come from a search across the whole methylome. We restricted it to a small, biologically chosen gene set and still picked up many of the same signals.

Did you find any organ-specific inflammatory signatures?

Not yet. The current clock was built from blood data. We want to see whether signatures trained in different organs give better or different predictions and respond differently to interventions. Only one graduate student is working on it right now, so progress is slower than we’d like, but organ-specific clocks are an important next step.

Inflammation is clearly more multifaceted than the simple division into pro- and anti-inflammatory factors suggests. Your March preprint examines IL-10, normally considered an anti-inflammatory cytokine, and suggests that chronic IL-10 exposure can instead promote inflammaging and tissue senescence. How does a protective signal become harmful, and how relevant might that be to normal human aging?

I should be careful because I’m a co-author, not the first or senior author, and the paper is still being revised. But, the basic idea is that cytokines probably have an optimal range. You need IL-10 to resolve inflammation, but if it stays too high for too long, it can turn harmful.

The work began in Margarida Saraiva’s lab, which mainly studies tuberculosis. In mice with sustained IL-10 overexpression in CD4+ and CD8+ T cells, those cells were reprogrammed. They became highly inflammatory, entered several tissues, and were linked to tissue dysfunction and signs of aging.

So, we need to understand the right range, not just whether a cytokine is “good” or “bad.” We’re not going to solve this one cytokine at a time, and we can’t simply suppress the immune system because it still has to fight infections.

That’s why I’m cautious about spectacular intervention studies. IL-11 inhibition extends lifespan in lab mice, but what happens in a natural environment? If you shut down a major pathway, perhaps the animals become worse at fighting infection.

The message isn’t that IL-10 is bad. It’s that too much for too long can be bad, and the same may be true for other “anti-inflammatory” cytokines.

In UK Biobank data, higher blood IL-10 was linked to a small increase in mortality risk, although the result was variable and shouldn’t be overinterpreted. So, dose, timing, and context matter more than the simple pro- versus anti-inflammatory label.

That seems like a recurring problem in aging research. We arrive with a simple intervention: this factor is elevated, let’s suppress it; that one is reduced, let’s increase it. Only later do we begin to understand the network. The mouse environment may also be a major confounder, especially for inflammation and immune aging. Lab mice live in unusually protected conditions. Rapamycin can suppress inflammation and some immune responses, and the mice live longer, but how well does that translate to humans who are exposed to many more pathogens?

I agree. I use mice, so I have to work within those limits, but it’s an important problem. One interesting experiment would be to give young lab mice defined inflammatory challenges – viruses, bacteria, LPS, TNF-α – and then see how those exposures change their later trajectory. We’ve started smaller in vitro proof-of-concept work.

My hypothesis is that if young cells get the right amount and pattern of inflammatory stress, they may become more resilient rather than older. It’s still very early and speculative, but some preliminary observations make us want to pursue it, at least in immune cells.

I’m also becoming more interested in non-immune cells. We see inflammatory signatures rise quite strongly in many of these cells with age.

We usually focus on two sources of age-related inflammation: immune cells and senescent cells. You are suggesting that apparently non-senescent, non-immune cells can also participate actively in inflammatory signaling.

Yes. The circuit linked to accelerated transcriptomic age is overexpressed not only in immune cells but also in non-immune cells. We see this clearly in the kidney, where several non-immune cell types become strongly pro-inflammatory with age even without the classical signs of senescence.

It makes sense. When a cell is in danger, it has to tell the immune system and nearby cells that something is wrong. Virus-infected cells do this through interferons. We see a similar pattern with MIF, macrophage migration inhibitory factor. Many cell types seem to express and release MIF when they’re under stress, whether from DNA damage, loss of proteostasis, or something else.

The idea is that non-immune cells start releasing inflammatory signals in response to the damage they build up over time. Those signals could amplify inflammation locally and perhaps eventually across the body.

We see it in the tissue too. In liver and kidney histology, many non-immune cells stain strongly for the marker linked to accelerated inflammatory aging. So, inflammaging isn’t simply an old immune system attacking passive tissues. The tissues themselves may join in.

I also wanted to discuss your 2024 paper on age-associated clonal B cells. I have long been fascinated by clonal expansion, including CHIP, and its relationship to aging and malignancy. What did you find?

I love that paper. It’s one of my favorites, and I want to stress that Anastasia Shindyapina and I were co-first authors.

We hadn’t planned the project when I joined Vadim’s lab. Anastasia and I became obsessed with it during a different intervention study. Some old control mice had very enlarged spleens, and at first we didn’t know whether B cells, T cells, or something else were responsible.

Around the same time, two relevant studies came out. One, from the late Angelika Amon’s group at MIT, linked larger cell size to senescence and aging. Another cross-species study connected larger cells in one tissue with shorter lifespan. So cell enlargement looked like a possible sign of accelerated aging.

We also knew that old C57BL/6 mice often develop B-cell lymphoma. We asked a simple question: are B cells from old mice larger than those from young mice? That same day, with only two young and two old animals, we saw a huge difference. The old B cells were much larger. We thought they might enlarge with age, become dysfunctional, and grow more vulnerable to cancer.

We then compared young mice, old controls, and old mice with B-cell lymphoma, usually identified after their spleens became greatly enlarged. With age, B-cell receptor diversity fell and clonality rose, especially in lymphoma. We then asked how a normal B cell might move toward cancer.

Age-associated B cells, or ABCs, were already known to build up with age and appear in autoimmunity and chronic infections. We thought they might give rise to a clonally expanded population we called age-associated clonal B cells, or ACBCs.

Using public single-cell data, we found markers separating follicular B cells, ABCs, and the clonal cells in lymphoma, and then confirmed them in the lab. ABCs were common in old mice without lymphoma, while ACBCs were abundant in lymphoma. That suggested a path from follicular B cells to ABCs and then to ACBCs.

CellChat pointed to CD22 signaling as one possible driver of the increase in cell size. Follicular B cells grew larger when exposed to ABCs, and blocking CD22 reduced that effect. So, communication between B-cell populations may help push cells toward the ACBC state.

The clones also had internal changes: somatic mutations, epigenetic changes including promoter hypermethylation, and c-Myc activation. These could give some clones an advantage and let them expand. The cells were IgM-positive and didn’t follow the usual germinal-center route.

So, it isn’t one event. The aged environment changes, B-cell diversity shrinks, some cells acquire mutations and epigenetic changes, and particular clones expand.

The big question was whether this mattered in humans. Mouse and human B-cell lymphomas aren’t identical, and the reviewers pushed us to be careful, but the mouse ACBC signature overlapped with human follicular lymphoma and diffuse large B-cell lymphoma. In human data, we also saw B-cell receptor diversity fall and clonality rise with age and found clonal B cells carrying the ACBC signature in people over 50.

So, ABCs may be a useful sign of age-related B-cell problems. They may lead toward autoimmunity, infection-related dysfunction, or cancer, and we still don’t know what decides the path, but they appear in all of those settings.

We also found that inhibiting mTOR or c-Myc in old mice reduced premalignant B-cell changes, so the process may not be irreversible, and those pathways could be targets for prevention.

The implications may extend beyond individual diseases. I have a pet hypothesis that clonal immune aging could be a limiting factor in extreme longevity. Clonal expansions are common in centenarians and supercentenarians, and perhaps they help impose a ceiling on maximum lifespan.

I agree it’s worth exploring. Clonal expansion may be manageable for a long time and then eventually start limiting resilience, but we need much more evidence.

Looking ahead, what is the roadmap for longevity therapies that target inflammation? In an optimistic, almost science-fiction scenario, how much could they affect human lifespan?

Potentially a lot, although I’m less sure that targeting inflammation alone can slow biological aging itself. Most chronic diseases have an inflammatory component, and many are linked to accelerated biological age. So, if we learn to control the right switches – keeping helpful inflammation while reducing harmful inflammation – we could probably extend lifespan by delaying chronic disease.

Whether that changes the aging process itself is harder to say, because many other things are happening, but even if it mainly separates healthy aging from disease and compresses morbidity, the effect could still be big.

We’re still early. As this conversation shows, there are many basic things about inflammation that we still don’t understand.

What are you personally planning to do to move the field in that direction?

I see three main directions. First, I want to find biomarkers that predict a resilient inflammatory state in humans. That would be a dream. We have a cohort of patients with chronic kidney disease that may be a good place to start.

Second, we want to reprogram immune cells so they support regeneration and perhaps lower biological age. This connects directly to inflammatory fidelity: finding the right switches and restoring a younger balance between helpful and harmful inflammatory programs.

The third direction is more speculative. I want to expose young animals and young cells to carefully controlled stimuli and ask whether the right kind of priming – even with things we normally consider damaging – can make them more resilient or biologically younger. It’s related to hormesis, but focused on inflammatory conditioning. The project is still embryonic, but I’m very excited about it.

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Date Posted: July 30, 2026

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Short-Term Stresses May Undermine Clock Results

A team of researchers has concluded that while methylation-based epigenetic clocks generally give reliable outputs when given the same inputs, short-term biological fluctuations can drastically change their results.

Technical and biological reliability

Epigenetic clocks are a way to measure biological age.

What Are Epigenetic Clocks

An epigenetic clock is a biochemical test that uses DNA methylation levels and accumulation of methyl groups on DNA to determine biological age. There are many different kinds of clocks, and these clocks are often considered to be the gold standard in aging biomarkers. Researchers are currently examining them as potential tools for uncovering the underlying mechanisms of aging, as biomarkers for anti-aging interventions, and as predictors of patient risk for morbidity and mortality.
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The authors make a clear distinction between technical and biological reliability. A technically reliable clock is one that consistently gives the same outputs when presented with the same input. A dozen researchers at a dozen different labs could present portions of the same blood sample to a technically reliable clock, and, as they are using identical material, it would give the same answer to all of them.

In the context of biological research, this is far from a trivial problem. The authors list a great many issues that may affect technical reliability, including differences between array platforms, differences in sample probing procedures including the chemistry of the probes used, and differences involving the handling, extraction, and storage of DNA. While no clock can fully account for the various ways that its input may be mishandled, some clocks that use principal components (PCs) have been designed to fight back against technical noise [1].

In general, all of the clocks that the researchers tested remained technically reliable under various laboratory conditions; While still in the ‘good’ range, CausAge was found to be the most vulnerable to such perturbations; SystemsAge and the PC versions of various clocks remained robust in the ‘excellent’ range. Certain disruptions in handling, such as slide placement, led to completely degraded technical reliability in many cases, and DNA extraction differences reduced reliability in three clocks. However, assuming proper and consistent handling, technical reliability appears to only be a mild concern.

A long-term clock can capture short-term effects instead

Biological reliability, however, is different. Aging clocks are supposed to measure long-term biological changes and remain unaffected by short-term perturbations in living conditions. However, the researchers’ findings, and the main thrust of their paper, are that they have significant problems with this and that their biological reliability is unrelated to their technical reliability.

For example, samples taken before and after eating yielded very different results in the vast majority of clocks. Only the PC version of the original GrimAge remained within the ‘good’ range of test/re-test reliability in this case; version 2 of GrimAge was very poorly reliable, as were the majority of other clocks. PhenoAge and the original Horvath clock remained in the ‘moderate’ zone after a meal.

Short-term stress yielded similar results; while many of the clocks were in the ‘moderate’ zone under stressful conditions, not a single one was considered ‘good’. Pollution exposure significantly degraded many clocks to the ‘good’ and ‘moderate’ ranges, and even a simple altitude change caused some unreliability, including in the PC version of GrimAge.

Ensuring reliability is difficult

The authors hypothesized that controlling for immune cell counts, which fluctuate under these conditions, may be a way of mitigating biological unreliability. This proved to be completely counterproductive; in nearly all of the clocks and nearly all of the conditions tested, this additional control led to a massive decrease in reliability instead. This led the authors to conclude that “changes in immune cell composition appear to reflect meaningful biological processes that are reproducibly detected by DNA methylation aging biomarkers.”

Of course, unreliable clocks cannot be used to yield reliable results. The authors claim that some of these clocks are so unreliable that their variation in z-scores fluctuates “across the full significance spectrum”, rendering their use completely untrustworthy regardless of the results generated using them.

Biological unreliability is in no way unique to methylation-based clocks [2], and the authors urge these results to be interpreted in that context. More traditional biomarkers, such as inflammatory compounds, are highly sensitive to perturbations such as exercise, markers such as hematocrit are very sensitive to hydration, and proteomic biomarkers fluctuate after meal consumption.

Additionally, the authors listed potential flaws in their own work; many of their findings were generated using cohorts of young adults, and there were no separate control groups to determine if specific perturbations or the simple passage of hours or days caused the variation in the clocks’ results. Further work should be done to ascertain more details about popular clocks’ reliability and any constraints, such as a fasting period, that should be adhered to in their use. If at all possible, future clocks should be developed to be insensitive to short-term alterations in epigenetic biomarkers.

Yes I will donate❤️

Literature

[1] Higgins-Chen, A. T., Thrush, K. L., Wang, Y., Minteer, C. J., Kuo, P. L., Wang, M., … & Boks, M. P. (2022). A computational solution for bolstering reliability of epigenetic clocks: implications for clinical trials and longitudinal tracking. Nature aging, 2(7), 644-661.

[2] Della Monica, C., Revell, V., Atzori, G., Laban, R., Skene, S. S., Heslegrave, A., … & Dijk, D. J. (2024). P-tau217 and other blood biomarkers of dementia: variation with time of day. Translational psychiatry, 14(1), 373.

Date Posted: July 28, 2026

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Montana’s Right-to-Try Law Enters a New Phase

Montana’s first experimental treatment review board has brought three longevity heavyweights into the state’s effort to expand access to experimental therapies.

How much regulation is too much?

Many people in the longevity field will tell you that regulation is holding it back. Sensible oversight of novel therapies is essential, but an overly cautious interpretation of “do no harm” can itself cause harm by delaying or denying access to potentially beneficial and life-prolonging therapies. The balance between protecting patients from risk and allowing them the freedom to seek better health and quality of life may currently be tilted too far toward the former.

Some people turn to therapies that are unproven even in terms of safety, sometimes administered by unlicensed practitioners. We have covered one case in which this led to loss of life and another in which it nearly did. Other people engage in medical tourism, seeking treatment in more permissive jurisdictions, which is expensive and not always safe. A different group has instead set its sights on advancing right-to-try legislation in the US.

The Montana way

Traditional right-to-try laws are generally limited to people with terminal illnesses, allowing them to try therapies that have not yet been fully approved by the FDA. Montana enacted a law along these lines in 2015: eligible products had to have completed Phase I and remain in an FDA-approved clinical trial. In 2018, the federal Right to Try Act became law, covering patients with life-threatening conditions who have exhausted approved treatments and cannot participate in a clinical trial involving the investigational product.

In 2023, Montana lawmakers passed SB 422, sponsored by State Senator Ken Bogner and supported by the Alliance for Longevity Initiatives and other members of the longevity community. In what was widely described as a US first, the law removed the terminal-illness restriction, potentially making the pathway available to any patient. Importantly, it did not require patients to exhaust standard care, only to have “considered all” FDA-approved options. Despite the polarized political climate, SB 422 enjoyed substantial bipartisan support.

While SB 422 removed restrictions, it did not provide investors and clinic operators with a licensing framework for establishing facilities. This was addressed in the follow-up bill, SB 535, which passed on a knife-edge in 2025.

It was designed to create that missing infrastructure by establishing a new category of health facility: the experimental treatment center. Such centers can charge for treatment and establish payment arrangements involving digital or alternative currencies – an unusual provision consistent with the legislation’s entrepreneurial and biohacking roots. The bill also loosened its predecessor’s language further, requiring patients only to have “evaluated other” approved options.

Welcome aboard

Under final rules that took effect earlier this month, an experimental treatment center must establish or contract with an experimental treatment review board, or ETRB. Board members may have no conflicts of interest involving the centers they review. ETRBs are envisioned as an important guardrail intended to improve patient safety.

The first such board has now been formed, and developers can submit eligible therapies for review for a fee of $12,500. Most eligible treatments will have completed Phase I, although Montana law also permits an alternative route based on equivalent documented safety evidence. Phase I trials primarily investigate safety and dosage and generally do not establish the treatment’s efficacy. Importantly, approval by the board does not amount to FDA approval or confer any federal legal status.

The five-member board includes three prominent figures in the longevity field: Matt Kaeberlein, a longevity researcher affiliated with the University of Washington; Jamie Justice, executive vice president of XPRIZE’s Health Domain; and Felipe Sierra, former director of the Division of Aging Biology at the National Institute on Aging. The other two members are bioethicist Jessica Flanigan and Montana oncologist James Burke.

The caliber of the board lends immediate credibility to the initiative, which was launched by Infinita, an organization founded by Niklas Anzinger and based in the Próspera special economic zone on the Honduran island of Roatán. “It’s been a lot of work, almost three years since the first bill,” Anzinger said. “Montana’s framework has been strongly influenced by the wishes of the longevity community. A patient does not need a defined disease state to be eligible – which is important because aging is not classified as a disease. This is a genuine first and only in recent history.”

Setting an example

Dr. Kaeberlein has long argued that the current development and approval process for new therapies is too slow and expensive. At the same time, he has frequently criticized the “Wild West” approach to longevity medicine.

“What interests me about Montana’s approach is that it attempts to create a middle ground,” he said. “Rather than pushing patients toward medical tourism or unregulated clinics, it seeks to establish a framework with independent review, physician oversight, informed consent, and systematic data collection. Whether that framework ultimately succeeds remains to be seen, but I believe it’s worth trying to make it as rigorous and scientifically credible as possible. That’s why I agreed to participate.”

“I joined Montana’s ETRB because this was too important an opportunity to pass up,” said Justice. “In many cases, testing of experimental therapies has moved offshore, and Montana has a chance to be at the forefront of bringing it back onshore. The board provides an opportunity for promising treatments to move forward, but with transparency and accountability built in from the start.”

Justice noted that, to avoid conflicts of interest, she will recuse herself from reviewing or making decisions involving competing teams, advisors, or other groups affiliated with XPRIZE Healthspan.

Given how narrowly SB 535 passed last year – and the reservations raised by both Democrats and Republicans – the first ETRB has an opportunity to address some of those concerns. By conducting rigorous reviews and producing meaningful safety and outcome data, it could offer a model for other states and, perhaps eventually, for federal legislation. Montana rules require review boards to publish annual summaries covering the treatments reviewed, safety outcomes, serious adverse events, and general review timelines.

“Local scientific review boards are a big part of China’s and Australia’s clinical trial success,” said Anzinger. “US states can really innovate before Washington catches up, and in the process generate valuable insight for national reform.”

Yes I will donate❤️

Date Posted: July 27, 2026

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How the Immune System Makes Sun Damage Worse

In Aging Cell, researchers have published an explanation of how neutrophil extracellular traps (NETs) worsen UVB damage and how inhibiting them alleviated this damage in a mouse model.

When defenders just make things worse

Immune activation is a common response to damage, as the immune system often perceives such damage as a pathogenic attack. Activation of immune system components in the absence of actual pathogens is known as sterile inflammation, and it is a frequent subject of aging research; chronic sterile inflammation is known as inflammaging.

Chronic Inflammation

Chronic inflammation refers to a persistent, low-grade buzz of immune activity that settles into the body without the drama of an infection or obvious injury. In the world of aging, this slow, smoldering fire is often called inflammaging, a term coined by Claudio Franceschi to capture the systemic, hard-to-detect inflammation that creeps in with advancing years.
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Damage done by UVB radiation from the sun causes an immune reaction that brings neutrophils into the skin. Exposed to this radiation themselves, these immune cells react by flooding the area with inflammatory cytokines, recruiting even more neutrophils and creating systemic inflammation that can even affect the kidneys [1].

NETs are created when neutrophils destroy themselves in a controlled demolition that releases proteins and DNA from their nuclei, and as their name suggests, NETs trap and kill pathogens. However, in sterile inflammation conditions, excessive NETs lead to autoimmune disorders, including rheumatoid arthritis [2], and previous work has found that reducing NETs alleviates UVB-related skin damage in mice [3]. This research builds upon that work, focusing on PAD4, a nuclear enzyme that is required for NET formation [4].

Stopping NETs at their source

The researchers first examined tissue samples derived from the lesions of human patients with actinic keratosis or chronic actinic dermatitis, two conditions that are related to sun damage of the skin. Compared to a control group, these samples had increased numbers of NETs.

They then began experimenting on mice, exposing the skin of wild-type Black 6 mice to UVB radiation and giving some of the exposed mice GSK484, a compound that inhibits PAD4. Compared to the untreated mice exposed to UVB, the GSK484-treated group had much less visible skin damage and reduced skin erosion, confirming previous research [5]. While it did not fully protect the mice from UVB damage, skin thickening, inflammatory biomarkers, and measurements of oxidative stress were all significantly reduced compared to the untreated group.

Cellular death by apoptosis was reduced as well. Fibroblasts and keratinocytes normally die in this way when exposed to UVB, but the rate of apoptosis, according to multiple biomarkers, was substantially reduced when GSK484 was administered.

RNA sequencing was performed to determine the pathways involved. The JNK branch of the well-known inflammation pathway MAPK, which was previously reported to be involved in NET-related damage [6] and was found to be linked to UVB damage in this study, was strongly inhibited by GSK484.

HaCaT cells, a line of immortalized human skin cells, were used in another experiment. The researchers exposed neutrophils to UVB radiation in order to generate NETs, which were then delivered to these cells. At 4 milligrams per liter of NETs, the HaCaT cells became unable to proliferate, began expressing inflammatory cytokines, experienced oxidative stress, and activated the JNK pathway, leading to apoptosis. However, exposing NETs to DNAse I before delivery degraded them, significantly reducing their negative effects on HaCaT cells.

A receptor may be a target

The researchers then investigated CCDC25, a gene in keratinocytes that responds to NET exposure. HaCaT cells that had their RNA expression of this gene silenced barely reacted to NETs, having no measurable increase in the JNK pathway and only slightly increased apoptosis.

These results were confirmed in mice. Using an adeno-associated virus (AAV) to block CCDC25 in UVB-exposed mice yielded similar results to GSK484 treatment: inflammation was significantly decreased, additional skin thickness was reduced, and markers of oxidative stress were lessened compared to the UVB-exposed and untreated control group.

This research opens up new avenues for potential treatments that might reduce long-term sun damage. While stopping the radiation itself can only be done through direct preventative measures, the immune system’s role in worsening this damage may be a treatable target. Preventing unnecessary NET formation may help curb inflammaging and reduce skin damage.

Yes I will donate❤️

Literature

[1] Skopelja-Gardner, S., Tai, J., Sun, X., Tanaka, L., Kuchenbecker, J. A., Snyder, J. M., … & Elkon, K. B. (2021). Acute skin exposure to ultraviolet light triggers neutrophil-mediated kidney inflammation. Proceedings of the National Academy of Sciences, 118(3), e2019097118.

[2] Fousert, E., Toes, R., & Desai, J. (2020). Neutrophil extracellular traps (NETs) take the central stage in driving autoimmune responses. Cells, 9(4), 915.

[3] Inaba, I., Hiramoto, K., Yamate, Y., Morita, A., Tsutsumi, T., Yasuda, H., & Sato, E. F. (2024). Inhibiting neutrophil extracellular traps protects against ultraviolet B-induced skin damage: effects of Hochu-ekki-to and DNase I. International Journal of Molecular Sciences, 25(3), 1723.

[4] Mutua, V., & Gershwin, L. J. (2021). A review of neutrophil extracellular traps (NETs) in disease: potential anti-NETs therapeutics. Clinical reviews in allergy & immunology, 61(2), 194-211.

[5] Inaba, I., Hiramoto, K., Yamate, Y., Morita, A., Tsutsumi, T., Yasuda, H., & Sato, E. F. (2024). Inhibiting neutrophil extracellular traps protects against ultraviolet B-induced skin damage: effects of Hochu-ekki-to and DNase I. International Journal of Molecular Sciences, 25(3), 1723.

[6] Hu, Z., Hua, X., Mo, X., Chang, Y., Chen, X., Xu, Z., … & Song, J. (2023). Inhibition of NETosis via PAD4 alleviated inflammation in giant cell myocarditis. IScience, 26(7).

Date Posted: July 24, 2026

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NYC Woman Dead After Receiving a “Longevity Infusion”

According to the experts that we spoke to, the death, which followed an intravenous NAD⁺ infusion that went catastrophically wrong, underscores the risks of unproven treatments and the need for rigorous longevity medicine.

Earlier this week, Elizabeth Baron, a 27-year-old woman from New York City, died after receiving an intravenous infusion at a local “wellness clinic.” The procedure was performed by 55-year-old Luis Rojas Cabrera, the owner of Bereshit Lifestyle Center. Cabrera was taken into custody by the NYPD and charged with reckless endangerment and unauthorized practice of a profession. He was later released without bail but ordered to surrender his passport. Cabrera claims to have completed his medical training in the Dominican Republic, but he is not licensed to practice medicine in the United States.

A popular but misused coenzyme

The tragic incident is directly connected to the longevity field: the infusion Baron received was supposed to contain NAD⁺ (nicotinamide adenine dinucleotide), a coenzyme central to energy production and DNA repair and a popular subject of longevity research.

NAD⁺ levels decline with age in some tissues [1], and the molecule has been linked to aspects of aging biology by multiple studies. NAD⁺ supplementation has significant appeal but is not easily achievable, as the molecule is rapidly metabolized. Most human research has therefore focused on the precursors NR and NMN, which can reliably raise blood NAD⁺ after oral administration.

NR can extend lifespan in yeast [2], and both NR and NMN have improved numerous age-related outcomes in rodents [3]. The lifespan evidence is less consistent: NR improved survival in a 2016 study [4], but failed to extend lifespan in either sex in the National Institute on Aging’s rigorous Intervention Testing Program (ITP) [5].

Human data is currently even less convincing, which has not stopped NAD⁺ and its precursors from becoming a fad in longevity circles. Numerous supplements can be bought online, including NAD⁺ nasal sprays and patches, and then there are NAD⁺ infusions, which, despite appearing more “serious” to laypeople, are backed by particularly slim evidence.

The experts weigh in

“Stories like this are heartbreaking,” said Dr. Matt Kaeberlein, a longevity researcher, University of Washington affiliate professor, and CEO and co-founder of Optispan. “Unfortunately, it isn’t the first time someone has been seriously harmed – or killed – while pursuing an unproven ‘longevity’ therapy. We still don’t know exactly what happened in this case, and it’s important to wait for the medical examiner’s findings before jumping to conclusions about the specific treatment involved. But the broader lesson is one I’ve been repeating for years: every experimental intervention comes with unknown risks. Those risks may come from the biology of the therapy itself, from manufacturing or quality-control problems, or simply from errors in preparation or administration.”

One of the cases that Kaeberlein is referring to happened last year at RAADfest, a popular gathering of longevity enthusiasts. It, too, involved injections offered in a setting where some of the practitioners reportedly were not properly licensed. The injections supposedly contained peptides, chains of several amino acids that can perform various biological actions. Two people almost died as a result.

In neither case do we yet know whether the reaction was caused by the purported active ingredient, contamination, incorrect preparation or dosing, or another aspect of administration. Unfortunately, what the general public will remember – and what will certainly resonate with its stereotypes – is that those longevity treatments turned out to be dangerous, and this one turned out to be deadly.

“The danger increases dramatically when these interventions are provided by unlicensed practitioners, through offshore clinics, or obtained through unregulated channels, whether that’s IV infusions, stem cells, or research-grade peptides purchased over the internet,” cautioned Kaeberlein.

Cabrera seems to clearly fit that bill, with his website offering a wide array of seemingly unrelated treatments alongside bombastic ‘scientific’ claims. One page features “a personalized Wellness Kit with the combination of over 100 components.” There is no indication that such a complex, personalized combination has been rigorously tested as a whole for safety, efficacy, or possible interactions among its components.

The story also reflects the gap between intense public demand for interventions that promise better health and longevity and the much slower progress of clinical science. In fact, the list of proven longevity treatments is extremely thin and headlined by “boring” lifestyle interventions such as diet and exercise. To many people, real longevity medicine – a nascent but quickly developing field – seems less glittery than the pseudoscientific talk of modern snake oil salesmen.

“Healthy Longevity Medicine is a medical discipline and, like every other medical discipline, it must be grounded in evidence, clinical governance, and patient safety,” said Dr. Andrea Maier, Oon Chiew Seng Professor in Medicine at the National University of Singapore and a longevity medicine pioneer trying to bring it to the masses. “We have created tremendous public interest in healthy longevity, but we have not done enough to educate the public about what is proven, what is experimental, and what remains unvalidated. The solution is not to question the field itself, but to strengthen physician education, international standards, and appropriate regulation so Healthy Longevity Medicine develops with the same scientific rigor and accountability expected of every other branch of medicine.”

“Alongside the need for more robust evidence and well-conducted safety trials, we also need to pay much greater attention to the potential adverse effects of different compounds, as well as the safety of their sourcing and manufacturing,” said Dr. Evelyne Bischof, Professor at Shanghai University of Medicine and Health Sciences and President of the Healthy Longevity Medicine Society. “When a substance is neither FDA-approved nor recommended by professional guidelines, and is often produced without rigorous independent quality control, traceability, or verification by accredited laboratories, there are important safety concerns that simply cannot be overlooked. It is deeply unfortunate that they are so often only recognized after tragic events like this occur.”

“I understand why people are eager to try the next promising intervention, but enthusiasm should never replace evidence or basic safety standards,” added Kaeberlein. “My advice remains the same: focus first on the interventions that have actually been shown to improve health and reduce disease risk, and when medication is appropriate, work with a qualified healthcare professional and stick to FDA-approved drugs from legitimate sources.”

Yes I will donate❤️

Literature

[1] Janssens, G. E., Grevendonk, L., Perez, R. Z., Schomakers, B. V., de Vogel-van den Bosch, J., Geurts, J. M., … & Hoeks, J. (2022). Healthy aging and muscle function are positively associated with NAD+ abundance in humans. Nature Aging, 2(3), 254-263.

[2] Belenky, P., Racette, F. G., Bogan, K. L., McClure, J. M., Smith, J. S., & Brenner, C. (2007). Nicotinamide riboside promotes Sir2 silencing and extends lifespan via Nrk and Urh1/Pnp1/Meu1 pathways to NAD+. Cell, 129(3), 473-484.

[3] Mills, K. F., Yoshida, S., Stein, L. R., Grozio, A., Kubota, S., Sasaki, Y., … & Imai, S. I. (2016). Long-term administration of nicotinamide mononucleotide mitigates age-associated physiological decline in mice. Cell metabolism, 24(6), 795-806.

[4] Zhang, H., Ryu, D., Wu, Y., Gariani, K., Wang, X., Luan, P., … & Auwerx, J. (2016). NAD+ repletion improves mitochondrial and stem cell function and enhances life span in mice. Science, 352(6292), 1436-1443.

[5] Harrison, D. E., Strong, R., Reifsnyder, P., Kumar, N., Fernandez, E., Flurkey, K., … & Miller, R. A. (2021). 17‐a‐estradiol late in life extends lifespan in aging UM‐HET3 male mice; nicotinamide riboside and three other drugs do not affect lifespan in either sex. Aging cell, 20(5), e13328.

Date Posted: July 23, 2026

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More Autophagy Reduces Toxin-Induced Kidney Failure in Mice

Autophagy, which increases in younger mice under toxic stress, does not increase in older mice and leaves them susceptible to acute kidney injury (AKI). Increasing autophagic flux by targeting a key molecule, transcription factor EB (TFEB), alleviates some of this damage.

An acute disease with lasting effects

AKI is a rapidly developing condition that causes patients to lose kidney function within days, sometimes within hours. In severe cases, kidney dialysis may become required to save the patient. Aging is a risk factor for AKI, for both incidence and severity [1], and in older people, it frequently leads to systemic inflammation and death [2].

In intensive care settings, blood poisoning (sepsis) caused by invading pathogens is a common cause of AKI [3]. However, while it is possible to artificially purify the blood and administer drugs to kill off pathogens, there are currently no methods of directly treating AKI.

The researchers have hit upon TFEB as a potential avenue for such a treatment. We have previously reported that this protein improves the maintenance of other proteins and increases cellular survival in senescence due to its effects on autophagy, a cellular maintenance process in which cells consume their own organelles. TFEB is directly related to autophagy, directly activating several associated proteins [4], and substantial previous work has found that TFEB is downregulated in various models of AKI, including septic AKI [5].

Older mice are less poison resistant

This paper’s first experiment involved administering lipopolysaccharide (LPS), a poison that is known to induce AKI, to 2-month-old and 18-month-old mice. After LPS administration, creatinine, blood urea nitrogen (BUN), tubular damage, and many other biomarkers of kidney damage were higher in the older mice than the younger mice.

LC3, a marker of autophagy, was slightly higher in the older mice before LPS administration. However, after LPS administration, LC3 was notably upregulated in the younger mice but not significantly upregulated in the older mice, and LPS caused autophagic flux to be twice as high in the younger animals as the older animals.

A cellular experiment found this to be related to senescence; ordinary kidney cells upregulated LC3 in response to this toxin, while senescent cells were unresponsive in this respect, and cells derived from older animals were less responsive from cells derived from younger animals. LC3 was found within puncta within the senescent cells, but it was not flowing freely, reflecting a lack of autophagic flux rather than an increase.

Administering Tat-Beclin 1, a peptide that directly induces autophagy, to kidney cells diminished the damage caused by LPS. Chloroquine, which inhibits autophagy, increased this damage, leading to both increased markers of cellular senescence and increased cellular death by apoptosis. Therefore, the relationship appears to be bidirectional; senescent cells exhibit less autophagy, and a lack of autophagy under toxic stress conditions contributes to cellular senescence.

Using TFEB to fight back

These results were confirmed by a gene expression analysis, which found significant decreases in autophagy-related genes in older mice compared to younger ones. One of the most downregulated proteins was TFEB; normally, older and younger mice express similar levels of TFEB, but LPS exposure caused TFEB in younger mice to decrease while it decreased even more in older mice. This finding was confirmed in cells, with LPS causing senescent cells to express significantly less TFEB than similarly treated non-senescent cells.

Using RNA to force senescent cells to express more TFEB under LPS conditions partially restored autophagy to these cells. Other autophagy-related genes were increased by this expression, and inflammatory cytokines were decreased.

The researchers then tested a curcumin analog, C1, which increases the nuclear translocation of TFEB, in older kidney cells exposed to LPS and a population of older mice also exposed to the toxin. In cells, this treatment improved autophagy by encouraging the beneficial translocation of TFEB even though it did not increase the total amount. In mice, this treatment partially but significantly reduced multiple markers of kidney damage, including creatinine, BUN, and NGAL, an established biomarker of kidney injury.

This work was done in a group of toxically injured mice and may not reflect conditions for real kidney patients. However, the findings are promising within this context. It remains to be seen whether C1 or another autophagy enhancer can ameliorate the damage caused by sepsis-induced or other AKI.

Yes I will donate❤️

Literature

[1] Hsu, R. K., McCulloch, C. E., Dudley, R. A., Lo, L. J., & Hsu, C. Y. (2013). Temporal changes in incidence of dialysis-requiring AKI. Journal of the American Society of Nephrology, 24(1), 37-42.

[2] Rex, N., Melk, A., & Schmitt, R. (2023). Cellular senescence and kidney aging. Clinical Science, 137(24), 1805-1821.

[3] Pais, T., Jorge, S., & Lopes, J. A. (2024). Acute kidney injury in sepsis. International journal of molecular sciences, 25(11), 5924.

[4] Di Malta, C., Cinque, L., & Settembre, C. (2019). Transcriptional regulation of autophagy: mechanisms and diseases. Frontiers in cell and developmental biology, 7, 114.

[5] Li, R., Zhao, X., Zhang, S., Dong, W., Zhang, L., Chen, Y., … & Liang, X. (2021). RIP3 impedes transcription factor EB to suppress autophagic degradation in septic acute kidney injury. Cell Death & Disease, 12(6), 593.

Date Posted: July 22, 2026

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The Progress and Future of Biological Aging Clocks

A recent review discusses the development of biological aging clocks, their capabilities and limitations, the discoveries they enabled, and possible future developments in this area [1].

How do we measure aging?

Developments in science and technology have allowed researchers to move beyond speculation and philosophical debates about aging to study its molecular underpinnings and the processes that govern it, creating opportunities to reverse them.

However, to measure the potential of an age-reversing intervention, we need to identify specific molecular metrics that indicate whether the body’s molecular clocks have been reversed or slowed and to what extent.

In their recent review, Tony Wyss-Coray and Eric Topol discuss the tools that enable such measurements. They focus on biological aging clocks, computational models designed to track the pace of aging and assess the biological age of an organism, organs, or cells. Those clocks “capture individual physiological differences relative to a larger reference population.” The authors elaborate on the progress made in this area and how these clocks can aid researchers in understanding diseases and extending healthspan.

Tick-tock

Aging clocks are a diverse set of tools. The first generation of biological clocks was built on DNA methylation patterns; the next generation of clocks incorporated additional molecular data, such as plasma protein levels and other large-scale arrays, as well as information such as hand strength, cognitive function, locomotion, eye and hearing acuity, and psychological testing, creating a plethora of clocks that focus on different metrics and exhibit varying predictive capacities across measured endpoints.

The field went even further, drawing on information from organ- and cell-derived plasma proteins to construct more advanced organs and cell-based clocks. Studies that used organ clocks showed that the age of each organ, as assessed by the clock, was associated with organ-specific diseases, such as Alzheimer’s disease being associated with brain age [2]. Additionally, among all the organ clocks, the brain and immune system clocks showed the strongest association with survival. Interestingly, the aging of one organ didn’t show strong correlations with the pace of aging in other organs, suggesting that organs age at different rates within the same individual [3]. Even more detailed than organ-based clocks are cell-type-specific clocks, which have found associations between accelerated biological aging in specific cell types and the risk of various diseases.

Beyond those clocks, there are other aging clocks that measure the pace of aging using various types of biological -omics data, including gene expression (transcriptomics), sugars and carbohydrates (glycomics), metabolomics, lipidomics, and microbiomics. While -omics technologies are popular among the researchers who design aging clocks, there are also clocks that use electronic health records; lifestyle factors; telomere length; standard lab tests such as HbA1c, C-reactive protein (CRP), and hemoglobin; various types of medical images such as magnetic resonance images, bone imaging, CT scans and histology slides; and physical parameters such as handgrip strength, lung function, balance, gait speed, blood pressure, and waist circumference.

Not all types of data are created equal in aging clocks. Using certain types of data can make it much more difficult to build an aging clock; for example, the complexity of the immune system makes it challenging to use it as a basis.

Despite these difficulties, researchers continue to pursue different approaches. The authors present an example of a sperm aging clock that uses small noncoding RNA expression data and has the potential to be used in the future to assess “health risks in offspring in fathers of advanced age” [4].

Limitations

As with every tool, there are limitations to using aging clocks. For example, the training sets on which the clocks were built may have demographic biases if they were created from limited populations. Despite that, such clocks, while not perfect, have been successfully used in many studies to predict all-cause mortality, cause-specific mortality, healthspan, various health outcomes, and biological age.

While aging clocks have been shown to correlate with various health outcomes, they do not establish causality; further research is necessary to do so. Additionally, aging clocks data were obtained primarily from population-level studies, so we do not know how useful those tools are at the individual level, and, as of now, aging clocks haven’t been established for clinical use. While there are products based on those clocks that are sold to the public, there is no standardization in the field and no regulatory approval for these products.

Much work done, an exciting future ahead

Biological aging clocks have already provided researchers with valuable insights into aging processes. Recent studies combining these clocks with other tools have established links between markers identified by epigenetic and proteomic clocks and various diseases, aiding researchers in understanding the mechanisms underlying disease and aging [5, 6]. Those new protein biomarkers have the potential to become drug targets to prevent various diseases [7, 8].

Some studies have provided data that links aging to “specific medications, lifestyle behaviors, menopause, foods, and occupations” [9]. They also found that epigenetic aging can be slowed down by interventions such as exercise [10] or, to a lesser degree, by omega-3 and vitamin D supplementation, multivitamins, the shingles vaccine, and GLP-1 drugs [11-14].

The technology behind aging clocks has made great strides, and we can expect further developments in this area as biological clocks have many potential uses. One of them is measuring early endpoints of geroprotective interventions under investigation; however, their use in clinical trials as a substitute for long follow-up periods requires further validation. Nevertheless, the authors believe that using a refined version of a clock in mainstream clinical care is possible in the foreseeable future, especially if the latest AI technologies are effectively employed to refine the models.

Probably the most important use for aging clocks is as a tool to help prevent age-related diseases. As the authors wrote, the opportunity to develop and properly use aging clocks lies in developing drugs to prevent diseases rather than treat them.

Yes I will donate❤️

Literature

[1] Wyss-Coray, T., & Topol, E. J. (2026). Biological aging clocks in health and disease. Nature medicine, 32(7), 2383–2394.

[2] Oh, H. S., Rutledge, J., Nachun, D., Pálovics, R., Abiose, O., Moran-Losada, P., Channappa, D., Urey, D. Y., Kim, K., Sung, Y. J., Wang, L., Timsina, J., Western, D., Liu, M., Kohlfeld, P., Budde, J., Wilson, E. N., Guen, Y., Maurer, T. M., Haney, M., … Wyss-Coray, T. (2023). Organ aging signatures in the plasma proteome track health and disease. Nature, 624(7990), 164–172.

[3] Kivimäki, M., Frank, P., Pentti, J., Jokela, M., Nyberg, S. T., Blake, A., Lindbohm, J. V., Oh, H. S., Singh-Manoux, A., Wyss-Coray, T., & Partridge, L. (2025). Proteomic organ-specific ageing signatures and 20-year risk of age-related diseases: the Whitehall II observational cohort study. The Lancet. Digital health, 7(3), e195–e204.

[4] Shi, J., Zhang, X., Cai, C., Liu, S., Yu, J., James, E. R., Liu, L., Emery, B. R., McMurray Bires, M. R., Torres-Arce, E., Rawal, H. C., Ramsay, J., Kunisaki, J., Zhou, C., Milstone, D. S., Patti, M. E., Yang, X., Jenkins, T. G., Quinlan, A., Cairns, B. R., … Chen, Q. (2026). Conserved shifts in sperm small non-coding RNA profiles during mouse and human aging. The EMBO journal, 45(4), 1362–1380.

[5] Ying K. (2025). Causal inference for epigenetic ageing. Nature reviews. Genetics, 26(1), 3.

[6] Schuermans, A., Pournamdari, A. B., Lee, J., Bhukar, R., Ganesh, S., Darosa, N., Small, A. M., Yu, Z., Hornsby, W., Koyama, S., Kooperberg, C., Reiner, A. P., Januzzi, J. L., Honigberg, M. C., & Natarajan, P. (2024). Integrative proteomic analyses across common cardiac diseases yield mechanistic insights and enhanced prediction. Nature cardiovascular research, 3(12), 1516–1530.

[7] Yao, M., Miller, G. W., Vardarajan, B. N., Baccarelli, A. A., Guo, Z., & Liu, Z. (2024). Deciphering proteins in Alzheimer’s disease: A new Mendelian randomization method integrated with AlphaFold3 for 3D structure prediction. Cell genomics, 4(12), 100700.

[8] Lind, L., Mazidi, M., Clarke, R., Bennett, D. A., & Zheng, R. (2024). Measured and genetically predicted protein levels and cardiovascular diseases in UK Biobank and China Kadoorie Biobank. Nature cardiovascular research, 3(10), 1189–1198.

[9] Sehgal, R., Borrus, D., Kasamato, J., Armstrong, J. F., Gonzalez, J., Markov, Y., Priyanka, A., Smith, R., Carreras, N., Dwaraka, V. B., DNAm aging biomarkers community, community Longevity interventional studies, & Higgins-Chen, A. (2024). DNAm aging biomarkers are responsive: Insights from 51 longevity interventional studies in humans. bioRxiv : the preprint server for biology, 2024.10.22.619522.

[10] You, Y., Chen, Y., Ding, H., Liu, Q., Wang, R., Xu, K., Wang, Q., Gasevic, D., & Ma, X. (2025). Relationship between physical activity and DNA methylation-predicted epigenetic clocks. npj aging, 11(1), 27.

[11] Bischoff-Ferrari, H. A., Gängler, S., Wieczorek, M., Belsky, D. W., Ryan, J., Kressig, R. W., Stähelin, H. B., Theiler, R., Dawson-Hughes, B., Rizzoli, R., Vellas, B., Rouch, L., Guyonnet, S., Egli, A., Orav, E. J., Willett, W., & Horvath, S. (2025). Individual and additive effects of vitamin D, omega-3 and exercise on DNA methylation clocks of biological aging in older adults from the DO-HEALTH trial. Nature aging, 5(3), 376–385.

[12] Kim, J. K., & Crimmins, E. M. (2026). Association between shingles vaccination and slower biological aging: evidence from a US population-based cohort study. The journals of gerontology. Series A, Biological sciences and medical sciences, 81(3), glag008.

[13] Li, S., Hamaya, R., Zhu, H., Chen, B. H., Pereira, A. C., Ivey, K. L., Rist, P. M., Manson, J. E., Dong, Y., & Sesso, H. D. (2026). Effects of daily multivitamin-multimineral and cocoa extract supplementation on epigenetic aging clocks in the COSMOS randomized clinical trial. Nature medicine, 32(3), 1012–1022.

[14] Maretty, L., Gill, D., Simonsen, L., Soh, K., Zagkos, L., Galanakis, M., Sibbesen, J., Iglesias, M. T., Secher, A., Valkenborg, D., Purnell, J. Q., Knudsen, L. B., Tahrani, A. A., & Geybels, M. (2025). Proteomic changes upon treatment with semaglutide in individuals with obesity. Nature medicine, 31(1), 267–277.

Date Posted: July 21, 2026

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Regular Training Erases Parts of Muscle Aging Signature

A new study suggests that regular planned exercise, not just being generally active, protects against certain aspects of muscle aging [1].

Are trained muscles younger?

With age, skeletal muscles lose strength, metabolic flexibility, and mitochondrial capacity. While regular exercise slows many aspects of functional aging [2], just how deeply training affects the molecular state of old human muscle is less known. Specifically, scientists have been trying to understand whether trained older muscles retain a more youthful molecular profile and whether physical fitness changes the way that older muscles respond to exercise.

These questions are difficult to answer since old people are generally less active than young people. Therefore, a molecular difference attributed to aging might actually reflect discrepancies in physical activity. The authors of a new study from Amsterdam UMC and Maastricht University, published in Nature Aging, tried to separate the two by comparing young adults with equally active older adults. To understand whether types of activity matter, they also included a group of highly trained older people.

The cohort contained 47 people overall: 11 young adults (average age 23), 16 trained older adults (average age 68), 15 normally active older adults, and 5 physically impaired older adults. “Trained” meant having at least three planned one-hour exercise sessions per week for more than a year. Physical impairment was defined as failing to pass the Short Physical Performance Battery (SPPB), a clinical test of balance, walking speed, and chair-standing ability.

Training seems to partially protect against muscle aging

The team examined muscles both at rest and immediately after exercise (one hour of cycling), reasoning that an acute physical challenge might expose differences that are not visible at baseline. Thigh-muscle biopsies were taken before and immediately after exercise. The researchers measured gene expression, metabolites, and lipid content.

The young group took almost the same number of daily steps (10,200) as the normally active older group (9,600). Time spent on higher-intensity activity was also broadly similar. Nevertheless, the groups were clearly separated at all three molecular levels.

Older muscles showed a particularly strong reduction in the expression of genes involved in mitochondrial respiration and energy production. Metabolomics pointed in the same direction: several metabolites in the NAD+ pathway were reduced, and NAD+ is a coenzyme needed for energy metabolism and many cellular stress-response and repair reactions. The comparison suggested that mitochondrial and energy programs decline with age even for people who remain reasonably active in daily life.

Sustained, structured training, however, appears to protect against these changes. More than half of the age-related changes in gene expression – in 56% of the upregulated and 57% of the downregulated genes – were absent in trained old adults. This effect was most prominent in mitochondrial and energy-metabolism genes, whose downregulation emerged as the clearest features of muscle aging. Some of the differentially regulated genes unaffected by training were related to synaptic or cell-signaling processes, tissue maintenance, and regeneration. The paper interprets the first group of changes as “preventable” by structured training and the second as “unavoidable.”

Reaction to acute exercise

The transcriptional response to an acute bout of exercise differed in young and older adults. However, the gap was the smallest in trained older adults; their response most closely resembled that of young people, while the impaired group was the most divergent.

The authors then examined genes that rose or fell following exercise in both young and normally active older adults. These shared exercise-induced changes included upregulation of several inflammation- and cellular stress-related genes, such as IL6, IL1B, and TNF. This acute reaction to exercise is well known from previous research [3], but here, it was most pronounced in trained adults.

The authors interpret this as a sign that healthier older muscles may be better able to activate an advantageous temporary stress and repair program when challenged. However, the research does not show a causative effect, only a correlation.

An important caveat is that exercise intensity was relative – 50% of the personal maximum – meaning that it might have been objectively higher in trained older adults than even in the young cohort, and the authors acknowledge this as a possible confounder. Regular strenuous exercise could have conditioned the trained participants’ muscles to mount a stronger acute response, rather than that response being what makes them healthier.

This study might be the most detailed analysis to date of the molecular features of muscle aging and how they correlate with structured training and physical activity. While not offering proof of causality, overall, it suggests that training muscles is as important in preventing certain aspects of aging as clocking in daily steps. On the other hand, it is not a miracle cure, and geroscience should be focused on solving the part of muscle aging that appears to be “exercise-proof.”

Yes I will donate❤️

Literature

[1] Janssens, G. E., Trętowicz, M. M., Grevendonk, L., Kotte, M., Scantlebery, A., Schomakers, B. V., … & Houtkooper, R. H. (2026). Delayed molecular aging, preservation of energy metabolism and enhanced exercise response in exercise-trained human muscle Nature Aging, 1-19.

[2] Valenzuela, P. L., Saco-Ledo, G., Morales, J. S., Gallardo-Gómez, D., Morales-Palomo, F., López-Ortiz, S., … & Lucia, A. (2023). Effects of physical exercise on physical function in older adults in residential care: a systematic review and network meta-analysis of randomised controlled trials. The lancet Healthy longevity, 4(6), e247-e256.

[3] Petersen, A. M. W., & Pedersen, B. K. (2005). The anti-inflammatory effect of exercise. Journal of applied physiology, 98(4), 1154-1162.

Date Posted: July 21, 2026

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Gabriel Cian on Building the 2060 Longevity Ecosystem

In this follow-up interview, we speak with Gabriel Cian about how the 2060 ecosystem has evolved since last year’s Forum, what he learned from the first edition, and how he is thinking about investment, scientific credibility, health optimization, policy, and the future of longevity in Europe.

Last year, we spoke about your path from software entrepreneurship into longevity and your goal of building a broader 2060 ecosystem. One year later, what has changed most in how you think about the mission?

What is the shortest path between two points? In mathematics, we would say it’s a straight line, right?

Yet a river never flows in a straight line from its source to the sea. Why is that?

Let me explain how this applies to the 2060 Foundation—and, more broadly, to the longevity field.

The mission of the 2060 Foundation is to defeat aging before the year 2060. At first glance, the obvious way to achieve this is to invest massively in R&D until we gain a precise understanding of the biology of aging and discover how to slow it down, stop it, or even reverse it. There’s no time to lose. 2060 is only 34 years away—it’s tomorrow. Understanding aging is incredibly difficult, so we should start funding large-scale research immediately, right?

Well, not so fast.

People are not ready for this. Governments are not ready for this. Much of the scientific community is not ready for this. Humanity, as a whole, is not ready for this. Trying to push society directly toward radical life extension meets fierce resistance at every level.

At the same time, however, the world is embracing preventive medicine at an exponential pace. Here, there’s no disruption, no futuristic biotech, no radical treatments—just healthier lifestyles, personalized diagnostics, and targeted supplementation. Nothing too controversial.

People resonate with this message. Governments support it because it can help contain healthcare costs. Investors are pouring massive amounts of capital into the space. Suddenly, longevity medicine seems like common sense.

I think you can see where I’m going with this.

The straight line from today to defeating aging would be to invest massively in R&D. But the resistance is simply too strong. That direct path doesn’t work.

By contrast, helping humanity move through an intermediate phase – embracing preventive medicine before becoming comfortable with the idea of radical life extension – is the path of least resistance. And it works.

Once this global movement toward preventive medicine is fully underway, even a small fraction of the enormous financial resources flowing into it can be redirected toward biotechnology and aging research. Sometimes, 1% of a huge pie is worth far more than 100% of a small one.

The biggest lesson I’ve learned over the past year is this:

In the real world, the shortest path is often not a straight line. It’s the path of least resistance.

What did you learn from the first 2060 Longevity Forum that shaped how you are approaching the 2026 edition?

The biggest insight from last year’s edition of the 2060 Forum was that financial resources are still so scarce in the longevity field that almost every participant had a strong financial incentive to attend.

VC funds were looking for new LPs. Longevity startups were raising capital. Investors were searching for promising investment opportunities. Sponsors were showcasing their products to generate revenue—and some of them were fundraising as well.

In a nutshell, everything revolved around capital.

This realization allowed us to rethink our communication strategy for this year’s edition. By aligning our messaging with the financial objectives of our audience, we were able to make our communication significantly more effective.

Looking back at the 2025 Forum, what were the most concrete outcomes? Were there partnerships, investments, or projects that came directly from people meeting there?

We’ve already received confirmation that several startups secured funding after pitching at last year’s edition of the 2060 Forum. We were thrilled to have played a part in making that happen.

Participants also loved the venue, and many are planning to return this year—this time with their partners and children. Southern France, a beautiful setting, outstanding sports facilities, and a unique blend of keynote speeches, meaningful conversations, swimming, and yoga sessions create an experience that is difficult to replicate elsewhere.

Another major outcome—although one that is much harder to quantify—has been planting the idea in investors’ minds that longevity may become one of the greatest investment opportunities of our time. Those ideas don’t transform into investments overnight. They take root, mature over time, and eventually reach a tipping point where investors begin allocating significant capital to longevity startups.

But perhaps the most significant outcome of the 2060 Forum has been the creation of the 3060 Fund of Funds. That is where the real epiphany happened.

But more on that later in this interview!

Were there any parts of last year’s event that did not work as well as you hoped, or that you deliberately changed this time?

Well, the most common piece of feedback we received from participants was about the food. It turns out that protein is just as important as vegetables – and all the other longevity-friendly nutrients.

The good news is that this is an easy fix, and we’re taking care of it this year!

The 2026 Forum appears to be larger and more ambitious than the first edition. What is substantively different this year beyond having more speakers or attendees?

For the 2026 edition, we’re aiming to go even further by bringing more investors to the event. We believe we have a responsibility to educate the investment community about the extraordinary opportunities in longevity, so this year we’re placing an even stronger focus on investors.

This should be great news for fundraising startups, as well as for investment funds looking to attract new LPs.

What did you learn from trying to bring scientists, startups, investors, clinicians, and policy advocates into the same room, and how has that shaped the 2026 program?

The biggest lesson we’ve learned is that longevity is not a vertical – it’s a mega-trend growing at an exponential pace, one that is reshaping multiple industries simultaneously: hospitality, healthcare, real estate, longevity clinics, fitness, insurance, tourism, and many others.

Conversations with participants from these different sectors made it clear just how broad and far-reaching the implications of longevity really are.

Another important insight from last year’s edition is that there is still no consensus on which industries, companies, or business models will emerge as the biggest winners. Will it be longevity therapeutics? Longevity clinics? Consumer digital health platforms? Advanced diagnostics? The truth is, nobody knows – and that’s precisely what makes the future so exciting.

This realization has strongly influenced the design of the 2026 program. We’ve placed an even greater emphasis on the diversity of our keynote speakers and on the range of longevity startups we’ll be showcasing on stage. We want investors to discover the broadest possible spectrum of opportunities across the longevity ecosystem.

Longevity conferences can sometimes become echo chambers for people who already agree with each other. How are you trying to include disagreement, skepticism, or more critical perspectives?

I don’t think the 2060 Forum is likely to become an echo chamber, because our mission is to educate investors about longevity as a new investment opportunity—not to promote a single narrative.

We want investors to understand both the opportunities and the risks, as well as the different timelines involved. That’s why we deliberately bring together experts with very different perspectives, who often disagree with one another.

For example, we’ll have:

Medical doctors who practice longevity medicine and place greater confidence in interventions that are already available than in long-term biotechnology projects.
Scientists who appreciate the extraordinary complexity of biology and believe that truly disruptive technologies may take many years to reach the market.
Pragmatic investors who focus on preventive medicine businesses—companies that may not revolutionize healthcare but are more likely to become profitable in the near term while delivering meaningful health benefits.
Long-term investors who back ambitious biotech startups, pursuing high-risk, high-reward opportunities.
Futurists who believe that artificial general intelligence is only a few years away and could dramatically accelerate the cure of many, if not all, diseases.
Startup founders developing breakthrough biotechnology who are advancing their therapies toward the clinic and the market, and who are optimistic about the results of the validation process in the coming years.

As you can imagine, these groups don’t always agree – and that’s exactly the point.

Our role is not to tell people what to think. It’s to expose them to the strongest arguments from different perspectives so they can form their own views.

Ultimately, our goal is not to provide all the answers, but to help our participants ask the right questions.

After speaking with investors through the 2025 Forum and the 2060 Investment Club, what do you now think investors most misunderstand about longevity?

Rather than saying investors misunderstand longevity, I would say that most of them simply don’t understand it yet – and for good reason. That’s exactly why the 2060 Forum exists.

On one side, there is biotechnology. The biology of aging is extraordinarily complex and largely inaccessible to most investors. Yet, this is where the truly disruptive breakthroughs are likely to emerge. This is where the next trillion-dollar company could be created. Because so few investors understand the field today, it remains a blue ocean with relatively little competition.

On the other side, there is preventive medicine: consumer health apps, advanced diagnostics, epigenetic clocks, and many other solutions that are already experiencing exponential growth. These businesses are easy to understand, highly relatable, and therefore already attract significant amounts of capital. But, because the barriers to entry are often relatively low, competition is intense. Investors can certainly generate attractive returns in this segment, but identifying the long-term winners is far from straightforward.

In my view, a sound longevity investment strategy combines both approaches. Yet many investors remain reluctant to invest in biotechnology and allocate most of their capital to preventive medicine instead.

I believe that’s a mistake.

Since last year, the 2060 ecosystem seems to have expanded beyond the Forum itself, including the Investment Club, Ikare.Health, and newer investment initiatives. How do these pieces fit together?

From day one, the vision of the 2060 Foundation has been to build a constellation of profitable, mission-driven ventures, each led by a dedicated and highly competent team, and all deeply interconnected in a mutually reinforcing ecosystem. That vision is becoming more tangible every day.

The 2060 Club makes longevity investing accessible to a broader audience by lowering the minimum investment ticket while carefully selecting high-potential startups.
The 3060 Fund of Funds enables qualified investors to gain diversified exposure to the entire longevity sector without the complexity of selecting dozens of startups or actively managing a private equity portfolio. In many ways, it is the closest thing to an S&P 500 for longevity—except that it invests in private companies rather than publicly traded ones.
Ikare helps people stay healthy for as long as possible by giving them access to the latest advances in preventive medicine. After all, investors are people too. Why invest in the longevity technologies of tomorrow if we don’t even benefit from the longevity technologies that already exist today?
Last but certainly not least, the global longevity community remains relatively small and geographically dispersed. And as social creatures, we eventually need to meet face to face.

That’s where the 2060 Forum comes in.

We want investors to shake hands with the founders they’ve backed. We want longevity physicians to meet their patients. We want Ikare patients to become investors, and investors to become Ikare patients.
In other words, we want every part of the longevity ecosystem to strengthen every other part.

Can you explain the 2060 Longevity Investment Club in practical terms? Who is it for, what role does it play, and how does it decide which startups or opportunities to present?

The 2060 Club is a community of investors who co-invest alongside me in carefully selected longevity startups.

Our goal is to invest in five to ten companies each year. Individual investments typically range from $5,000 to $20,000 per startup, allowing us to aggregate approximately $500,000 per financing round. For each investment, we create a dedicated Special Purpose Vehicle (SPV) that pools capital from all participating investors. I personally invest in every startup alongside our members.

The 2060 Club follows a straightforward and well-established venture capital model. It has two revenue streams: an annual membership fee and a 10% carried interest on successful exits.

The Club manages each investment throughout the life of the company until a liquidity event occurs, at which point the proceeds are distributed to investors.

Overall, the 2060 Club is an ideal solution for investors who want exposure to the longevity sector but lack the expertise to identify the best opportunities or the network and scale required to negotiate attractive investment terms.

When your team evaluates a longevity startup, what does the diligence process actually look like? Who assesses the science, the market, and the investment risk?

We often co-invest alongside longevity-focused venture capital funds such as Apollo Health Ventures and LongGame. Whenever possible, we leverage their due diligence as an additional layer of validation.

The broader 2060 Foundation ecosystem is also a significant advantage. Over the years, we’ve built strong relationships with universities, research institutions, leading scientists, and industry experts. In many areas of biotechnology, only a handful of people in the world have the expertise to fully understand what a company is developing. Being able to consult those experts is an invaluable part of our evaluation process.

My partner, Martial Trigeaud, brings decades of relevant experience to this effort. Before joining the 2060 Foundation, he was a serial entrepreneur in the medtech sector and later became the co-founder and General Partner of B21 Ventures, a venture capital fund focused on longevity.

Martial leads our due diligence process. His experience, network, and deep understanding of the field make him exceptionally well qualified for this role.

Has your threshold for what counts as investable longevity science changed over the past year?

I’m very bullish on disruptive biotechnology, and we will continue investing directly in these companies through the 2060 Club.

At the same time, we also invest in preventive medicine companies because they represent the path of least resistance for investors (as I explained earlier). They are easier to understand, easier to adopt, and attract significantly more capital today.

So yes, in a sense, our investment thesis has broadened. While we remain convinced that disruptive biotechnology will generate the largest long-term returns, we now also actively invest in preventive medicine companies as an essential part of the longevity ecosystem.

You have described longevity as a major investment opportunity, but biotech timelines are long and failure rates are high. How do you communicate the upside without encouraging unrealistic expectations?

Most of the time, we invest in biotechnology companies at very specific stages of their development. For example, we often invest when a company is close to completing Phase I or Phase II clinical trials, and is potentially just two or three years away from being acquired by a major pharmaceutical company.

Of course, there is never any certainty that such an outcome will materialize. But this illustrates an important point: investing in biotechnology is not necessarily riskier—or more long-term—than investing in many other sectors. When you invest at the right stage, the risk-reward profile can be remarkably attractive.

You have also discussed newer investment concepts around broader exposure to longevity, including 3060.vc. What are you trying to build there, and what problem does it solve for investors?

Let me tell you the story behind the 3060 Fund of Funds.

During last year’s edition of the 2060 Forum, a friend of mine, Martin Beaujouan—an exceptionally successful real estate investor—made an observation that completely changed the way I thought about longevity investing.

He pointed out that longevity is not a single industry. It’s an ecosystem that spans biotechnology, medtech, diagnostics, preventive medicine, nutrition, fitness, hospitality, real estate, insurance, and many other sectors. The field is simply too broad and too specialized for any individual investor to cover effectively.

To build a truly diversified longevity portfolio, you would need to invest in hundreds of startups, review thousands of investment opportunities every year, and possess deep expertise across multiple disciplines.

In short: mission impossible.

What we needed was the equivalent of the S&P 500 or the NASDAQ but for longevity: a single investment vehicle providing broad exposure to the entire longevity ecosystem.

Because there are still very few publicly traded longevity companies, an index fund isn’t a viable solution today. The closest equivalent is a fund of funds.

Our idea is simple. Each year, we select what we believe are the five best longevity-focused venture capital funds, based on factors such as track record, team quality, credibility, and historical performance. If each of those funds holds a portfolio of around 50 companies, our investors immediately gain exposure to roughly 250 startups. By carefully selecting funds with complementary investment strategies, we can provide broad exposure across the entire longevity landscape.

Today, there are roughly 50 venture capital funds dedicated primarily to longevity worldwide. As the industry matures, that number is likely to grow significantly. Our role is to continuously screen the market, evaluate these funds, rank them, and invest in the most compelling ones. The objective is to give our investors exposure to the longevity economy in much the same way that the S&P 500 provides exposure to the U.S. economy or the NASDAQ provides exposure to the technology sector.

Initially, we built this strategy for ourselves and a small group of close friends, but we quickly encountered another challenge. Many of the world’s leading venture capital funds require minimum commitments of around $500,000. Building a diversified portfolio across five funds therefore requires an investment of approximately $2.5 million.

The obvious solution was to bring together a community of like-minded investors so that we could invest alongside the world’s leading longevity funds.

That’s how the 3060 Fund of Funds was born.

To the best of my knowledge, it is the only investment vehicle specifically designed to give qualified investors broad, diversified exposure to the entire longevity sector through a single product.

Ikare.Health appears to focus on helping people act on today’s available longevity and preventive health tools. How do you distinguish responsible health optimization from overpromising or biohacking hype?

At Ikare.Health, we’re obsessed with the 80/20 principle. We constantly challenge our longevity physicians and health coaches with one simple question: “What are the 20% of interventions that will generate 80% of the health benefits for this particular patient?”

Ikare is the exact opposite of a service that overwhelms people with long lists of generic recommendations. Instead, we identify the one or two interventions that are likely to have the greatest impact for each individual.

For one person, the priority may be improving sleep. For another, it may be building muscle mass. For someone else, it could be reversing prediabetes or optimizing metabolic health. Whatever the priority, we translate it into clear, actionable steps that can be integrated into the patient’s daily routine.

This 80/20 approach naturally helps patients focus on what matters most, ignore unnecessary complexity, and consistently execute on the changes that will have the greatest impact on their long-term health.

What evidence threshold do you personally use before you are comfortable recommending or building around a health intervention?

I’m a man of extremes: very low-tech when it comes to preventive medicine, and very high-tech when it comes to biotechnology. 🙂

When it comes to my own health, I follow a set of simple, evidence-based principles:

Managing stress
Prioritizing both the quantity and quality of sleep
Eating an appropriate diet
Maintaining good mental health through meaningful relationships and a strong sense of purpose
Engaging in regular, varied physical activity
Using personalized diagnostics, such as genetic testing, blood biomarkers, VO₂ max assessments, and other objective measurements

The challenge isn’t knowing what to do – it’s doing it consistently.

These principles may sound like common sense, but following them requires persistence and the ability to stay on your own path instead of constantly being pulled back toward the habits of your surrounding environment. It becomes even more challenging when you recognize that every individual is different and that the optimal balance between these interventions varies from person to person.

Personally, I believe that once these fundamentals are in place, the returns from pursuing increasingly sophisticated optimization strategies diminish rapidly. Rather than spending more time and money chasing marginal gains, I think those resources are often better invested in advancing the longevity field itself—by supporting research and development, advocacy, or other initiatives that accelerate scientific progress.

Since last year’s Forum, have you seen any concrete movement from policymakers, or is longevity still mostly being driven by private capital?

Government officials are beginning to take an interest in the longevity field, but concrete initiatives remain modest.

Influencing public policy is both surprisingly easy and surprisingly difficult. On the one hand, it doesn’t necessarily require enormous financial resources – meaningful advocacy efforts can begin with budgets of around $50,000 per year. On the other hand, changing laws is a long-term endeavor that often requires 10 to 15 years of patient, persistent work by experienced advocacy professionals.

For now, our priority is to build sustainable revenue streams that will allow us to support these efforts over the long term. Once that financial foundation is in place, we intend to allocate part of those resources to advocacy and public policy initiatives designed to accelerate the development of the longevity field.

A recurring criticism of longevity is that it could become a field for wealthy early adopters. Given the high cost of conferences, clinics, and early-stage investment access, what does democratization mean in practice?

The biggest obstacle to the widespread adoption of longevity isn’t financial – it’s cultural. It’s a matter of mindset.

Many of the most powerful interventions are not expensive. In fact, they often cost less than the alternatives:

Practicing intermittent fasting often costs less than eating more frequently.
Walking, running, or exercising costs less than spending hours in front of Netflix.
Preventing disease is generally less expensive than treating it.
Getting eight hours of sleep costs less than regularly staying out late.
Building meaningful relationships and living with purpose can be far more valuable – and often less costly – than dealing with the consequences of chronic stress, loneliness, or poor mental health.
Quitting smoking and reducing alcohol consumption cost less than maintaining those habits.

Of course, changing behavior is much harder than making these comparisons. The challenge is rarely financial – it is psychological, social, and cultural.

The mission of the 2060 Foundation is to help make these ideas mainstream – to make healthy longevity aspirational, accessible, and, yes, even “sexy.”

It’s an ambitious mission, but we’re convinced the world is moving in that direction.

You have talked about building the South of France into a longevity hub. What parts of that are already real today, and what remains aspirational?

Today, most of our initiatives are virtual. Our teams and collaborators are spread across the world, working remotely, and that model has served us well. The projects are moving forward.

For now, we only come together in person for two days each year during the 2060 Forum. That’s valuable – but it’s not enough. We need a permanent home for the longevity ecosystem.

I imagine a high-end longevity campus in Southern France: a place where families who aspire to live according to the principles of healthy longevity can also work, build companies, conduct research, and collaborate every day. A place that truly embodies the ideal of a healthy mind in a healthy body.

It would be much more than a real estate project. It would be a living community and a catalyst for innovation.

That vision hasn’t become reality yet – but we still have 34 years until 2060. 🙂

If we speak again next year, what would you want to be able to say 2060 accomplished in 2026?

Our goal for 2026 is to establish the 2060 Foundation as the leading organization promoting longevity in Europe.

We’re building that visibility on multiple fronts: appearing on television, participating in podcasts and conferences, helping channel more investment into the longevity sector, and bringing people who have only recently discovered longevity into direct contact with world-class scientists, physicians, entrepreneurs, and investors.

We’re making steady progress—and we believe we’re on the right path to achieve that vision.

Date Posted: July 20, 2026

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Exosomes From Stem Cells Fight Liver Disease in Mice

Researchers have described a method of using exosomes derived from mesenchymal stem cells (MSCs) to fight harmful metabolic changes in the liver.

Another look at exosomes

This is far from the first attempt at using MSC-derived exosomes, particularly exosomes derived from MSCs originally taken from human umbilical cord tissue (HucMDEs derived from HucMSCs), to treat an age-related disease. For example, we have previously reported on such exosomes being used to fight sarcopenia in mice, and the researchers note previous work suggesting that they can be used to fight liver disease [1].

This research focuses specifically on autophagy, the maintenance process in which cells consume their own malfunctioning organelles. Autophagy is responsible for removing fatty droplets within liver (hepatic) cells [2], and a lack of autophagy leads to liver diseases such as non-alcoholic fatty liver disease (NAFLD) [3]. Previous research has found that increasing autophagy fights liver injury in a mouse model [4].

The authors began by ascertaining whether the human umbilical cord cells could be differentiated into bone cells (osteoblasts) and fat cells (adipocytes), then beginning to derive exosomes from them. These exosomes were labeled with a marker before being injected into the tail veins of mice, and then the livers were examined for the presence of this marker, confirming that the exosomes were successfully taken up into liver tissue.

Fighting unwanted liver fat

The next experiment involved three groups of animals: 8-week-old (young) mice, a control group of 18-month-old (old) mice, and an experimental group of old mice given HucMDEs. These mice were all male. While the control group of old mice was substantially heavier in body weight than the young mice, the treatment group was only slightly heavier. The control group had a substantial increase in blood glucose, while the treatment group was nearly indistinguishable from the young mice.

Four key markers of fatty liver disease, alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), and total cholesterol (TC), were tested. ALT had the strongest spike in the untreated old group, which was reduced to the levels of young mice. AST was similarly upregulated in the control group, and its levels were significantly leveled as well, although not quite to the levels seen in young mice. The TC results were similar to the ALT results, and the TG results were similar to the AST results.

“The above results demonstrate that aging induces liver dysfunction and dyslipidemia in mice, and that HucMDE administration can effectively improve liver function and normalize serum lipid levels in aging mice.”

Confirming this, the researchers also found substantial decreases in lipid deposition in the livers of the treatment group compared to the old group. SREBP1, a protein that encourages fat deposition, was increased with age but diminished with treatment, while PPARα, a protein that is involved in the destruction of such fat deposits, was substantially diminished with age and somewhat recovered with treatment. An in vitro analysis found that HucMDEs, but not exosomes derived from lung fibroblasts (HEDEs), had similar results in liver cells that had been driven senescent by palmitic acid (PA).

Effects against senescence

Similar results were found with two key senescence-related proteins, p16 and p21. In the old controls, both of these proteins were elevated in the liver; however, in the treatment group, the levels were similar to those of young mice. These results were likewise confirmed with in vitro testing, which found that HucMDEs but not HEDEs reduce a key senescence biomarker, SA-β-Gal, in PA-treated liver cells.

Autophagy was similarly increased by HucMDEs in these cells, with one key related protein, LC3, being increased by HucMDE treatment. Mouse experiments found similar results, with LC3 levels becoming more similar to those of young animals after treatment, although the reversal was not complete. Further experiments involving RNA silencing confirmed that HucMDEs reliably increase autophagic flux.

These effects were found to be due to THBS1, a protein that is highly expressed in HucMDEs but not HEDEs. Knocking down THBS1 in HucMSCs, and then deriving HucMDEs from them, created exosomes that were powerless to affect autophagy or senescence in liver cells. PPARα is responsible for THBS1’s effects within these cells; knocking down PPARα in the target cells similarly blunted the effects of useful HucMDEs.

The researchers note that there is no current drug therapy that is specific for NAFLD, so finding potential targets and therapies is a priority for the field. While these results are only, so far, in male mice, exosomes offer promise as a treatment method for this and other disorders involving aging and senescence.

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Literature

[1] Lou, G., Chen, Z., Zheng, M., & Liu, Y. (2017). Mesenchymal stem cell-derived exosomes as a new therapeutic strategy for liver diseases. Experimental & molecular medicine, 49(6), e346-e346.

[2] Sakane, S., Hikita, H., Shirai, K., Myojin, Y., Sasaki, Y., Kudo, S., … & Takehara, T. (2021). White adipose tissue autophagy and adipose-liver crosstalk exacerbate nonalcoholic fatty liver disease in mice. Cellular and molecular gastroenterology and hepatology, 12(5), 1683-1699.

[3] Qian, H., Chao, X., Williams, J., Fulte, S., Li, T., Yang, L., & Ding, W. X. (2021). Autophagy in liver diseases: a review. Molecular aspects of medicine, 82, 100973.

[4] Li, X., Gong, S., Chen, W., Zhao, Y., Fu, K., Zheng, Y., & Chen, J. (2023). Schisandrol A, a bioactive constituent from Schisandrae Chinensis Fructus, alleviates drug-induced liver injury by autophagy activation via exosomes. Bioorganic Chemistry, 139, 106751.

Date Posted: July 17, 2026

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Engineered Enzyme Reverses Age-Related Protein Damage

Scientists have engineered an enzyme that removes an advanced glycation end product (AGE) from proteins. This type of age-related modification, which affects protein function and can trigger inflammation, has previously been considered extremely hard to reverse [1].

Can we rejuvenate proteins?

Many proteins are continually broken down and replaced. Others, especially proteins of the extracellular matrix (ECM) – the collagen-rich material surrounding cells – can remain in the body for years or decades. During that time, they gradually accumulate unwanted chemical changes.

One major category of damage is glycation, which occurs when sugars and sugar-derived reactive molecules become spontaneously attached to amino acids in proteins without the reaction being mediated by an enzyme (nonenzymatically). Over time, some of these early modifications become chemically stable AGEs [2].

AGEs can cause harm by forming crosslinks between proteins, which makes tissues stiffer, or by altering the charge or shape of individual proteins. Some AGEs can also be recognized by immune or cellular receptors, triggering inflammatory signaling. The body has natural defenses that slow the accumulation of this type of damage, but, in general, it cannot be naturally reversed.

Removing these modifications has been one of the hardest problems in geroscience. A new study published in Nature Communications by scientists from Calico, Revel Pharmaceuticals, and the University of Colorado contains what might be the first proof that it can actually be done.

Going enzyme-hunting

The researchers studied a particular AGE, N^ε-carboxymethyl-lysine (CML), which is formed on the amino acid lysine, adding a carboxymethyl group to it. CML can impair the protein’s structure and function, and it can engage RAGE, the pro-inflammatory receptor for AGEs [3].

The authors searched for an enzyme capable of cleaving CML and found that several glycine oxidases could act on free CML, as part of the CML molecule chemically resembles glycine. However, initially none could act when CML was embedded in a peptide, a chain of several amino acids that the researchers used as a model instead of much longer proteins.

A glycine oxidase from the bacterium Bacillus subtilis did indeed convert free CML into normal lysine and two byproducts, but it did so very inefficiently. The researchers then looked at several of its “relatives.” One of them was able to bind free CML much better but still could not process peptide-bound CML, suggesting that the problem was physical access rather than chemistry: when CML is part of a protein, it’s harder for a glycine oxidase to engage it.

The authors found that a particular structural element (α9 helix) likely obstructed the enzyme’s access and searched existing databases such as AlphaFold for similar enzymes without that element. After examining north of 44 thousand candidates, they found one that showed weak but detectable activity on the model peptide.

Evolution, weaponized

To advance from this starting point to an enzyme that actually works, the team harnessed evolution itself, linking the desired enzymatic reaction to bacterial survival. They first created huge libraries of mutated enzyme variants and introduced them into an E. coli strain unable to grow without lysine. The bacteria were then supplied with CML (either free or embedded in a short peptide). Only cells carrying enzyme variants that could convert the modified lysine back toward its normal form were able to obtain enough lysine to form colonies. This allowed the researchers to pick the most promising variants and improve them further.

Across five rounds of mutation and selection, the authors progressively opened the active site, improved CML binding, stabilized the enzyme, and reduced dependence on the surrounding peptide sequence, producing the final variant of the enzyme they called CMLase. In the next experiment, the enzyme removed CML from a complete protein, modified bovine serum albumin, without degrading it. The researchers then confirmed CML-removing activity for several other proteins.

CMLase, however, did not achieve universal results. Some CML sites were more susceptible to “rescue attempts” than others, depending only partly on the protein structure at that particular spot. The exact reasons why some lysines can be restored more easily than others are still unclear.

Moving to naturally glycated proteins

Up to this point in the study, CML damage to proteins was engineered. It was crucial to see whether CMLase can act on naturally aged human proteins. The enzyme indeed reduced endogenous CML in soluble lens proteins from a 64-year-old human donor. Lens crystallins are exceptionally long-lived proteins, making the lens a useful tissue for studying decades of accumulated chemical damage.

CMLase also sharply reduced CML burden in aged human artery (by 70%) and skin (by 55%). Skin CML staining after treatment fell below that observed in 31-year-old skin. Importantly, these experiments were performed in very thin sections and did not demonstrate penetration into a living artery or intact piece of skin, where delivering the enzyme to its target might prove harder.

While a big milestone and an exciting proof of concept, the study had several other important limitations. For instance, the researchers did not perform functional rescue experiments that would determine whether treated proteins or tissues functioned better, and they did not test for immunogenicity; an enzyme of bacterial origin might trigger a human immune response.

CML is also a relatively easy target compared to some other AGEs. The next step might be tackling glucosepane crosslinks: glucosepane attaches itself to two collagen molecules (or two sites on the same molecule), restricting tissue elasticity, which is a major factor in aging.

Yes I will donate❤️

Literature

[1] Trabosh, N., Smith, J., Hsu, M. Y. H., Panja, S., Nagaraj, R., Olsson, N., … & Cravens, A. (2026). Reversal of protein chemical aging by enzymatic deglycation. Nature Communications, 17(1), 5926.

[2] Chaudhuri, J., Bains, Y., Guha, S., Kahn, A., Hall, D., Bose, N., … & Kapahi, P. (2018). The role of advanced glycation end products in aging and metabolic diseases: bridging association and causality. Cell metabolism, 28(3), 337-352.

[3] Kislinger, T., Fu, C., Huber, B., Qu, W., Taguchi, A., Du Yan, S., … & Schmidt, A. M. (1999). N ε-(carboxymethyl) lysine adducts of proteins are ligands for receptor for advanced glycation end products that activate cell signaling pathways and modulate gene expression. Journal of Biological Chemistry, 274(44), 31740-31749.

Date Posted: July 16, 2026

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Activating a Key Receptor Fights Thymic Involution in Mice

Publishing in Aging Cell, researchers have devised a way to delay the aging of the thymus by targeting GPR40, a key receptor in its epithelial cells.

The organ that involutes

The thymus trains a certain subset of immune cells, which are named T cells due to their relationship with it. As the thymus ages, its functional cells are gradually replaced with fatty tissue, weakening the immune system overall. This process is called involution, and stopping or reversing it has been a long-standing goal of research into aging.

Thymic involution has been linked to the aging of thymic epithelial cells (TECs), which maintain this organ’s form and ability to function [1]. Previous research has found that restoring these cells may be a viable path towards treating thymic involution and restoring immune function [2].

This paper’s focus is on GW9508, a compound that selectively activates GPR40, which has been previously investigated in its roles in metabolic disease [3] and aging [4]. While its anti-inflammatory effects have been previously documented [5], its potential role in the thymus has not.

A question of dosage

In their first experiment, the researchers utilized five groups of 17-month-old, naturally aged female Black 6 mice: a control group, a 12.5 mg/kg GW9508 group, a 25 mg/kg GW9508 group, a 50 mg/kg GW9508 group, and a group that received 50 mg/kg of GW9508 along with 2.5 mg/kg of GW1100, which deactivates the GPR40 receptor and neutralizes the canonical effect of GW9508. These treatments occurred every other day for a month.

Interestingly, the lower doses seemed to have more substantial effects above the control group, with the lowest dose appearing to have the greatest effect; the average thymus of these animals was roughly 50% heavier than that of the control group. As expected, the group that received the GW1100 along with GW9508 had the smallest average thymus weight. The spleen was not significantly affected by this treatment, and all of the treatment groups had markedly lower creatinine levels; the researchers interpret these results as suggesting a lack of liver and kidney toxicity and potentially improving kidney function.

Broad cellular effects

A closer look at the thymus demonstrated how GW9508 fights its involution in these animals. Multiple subsets of thymocytes were increased in number, including all four differentiation stages of a crucial double-negative subset. A very wide variety of specialized TECs were also increased as well. As expected, GW1100 reversed these beneficial effects, demonstrating that the GPR40 receptor is the cause.

The treatment had beneficial downstream effects, increasing the populations of CD3+ and CD4+ T cells along with multiple subsets of these cells. While CD8+ T cells were not affected to the level of statistical significance, many subsets of these cells were. Some of these subsets were naïve T cells, which have been previously linked to enhanced healthspan [6].

GW9508 also reduces senescence in TECs. Doxorubicin, a compound commonly used to induce senescence in cells, was administered in a sufficient quantity to cause senescence in 85% of the TECs in a control group. However, in the GW9508 treatment group, this proportion was reduced to only 20%. Genes related to the proliferation of these cells were upregulated, and cells that did become senescent appeared to die off more easily by apoptosis instead of staying around. Further experiments with GW1100 confirmed that these effects were indeed due to the GPR40 receptor.

The receptor is the cause

The researchers then further confirmed their results by using RNA that directly affects GPR40. Silencing GPR40 drove even young TECs towards senescence, as confirmed by multiple aspects of function and metabolism, while directly upregulating GPR40 caused the same effects as GW9508 administration.

This study was limited in key ways. Only 17-month-old female Black 6 mice were utilized in this study without a younger control group, and the thymic examination involved sacrificing the mice; no lifespan study was performed. There was also no pathogenic test of immune capabilities. The cellular study exclusively used doxorubicin and did not include replicative senescence. However, these findings are intriguing and suggest that GW9508 and GPR40 may be potential targets in the treatment of thymic involution.

Yes I will donate❤️

Literature

[1] Zhu, X., Gui, J., Dohkan, J., Cheng, L., Barnes, P. F., & Su, D. M. (2007). Lymphohematopoietic progenitors do not have a synchronized defect with age‐related thymic involution. Aging cell, 6(5), 663-672.

[2] Goronzy, J. J., & Weyand, C. M. (2019). Mechanisms underlying T cell ageing. Nature Reviews Immunology, 19(9), 573-583.

[3] Li, Y., Yu, H., Lopes-Virella, M. F., & Huang, Y. (2024). GPR40/GPR120 agonist GW9508 improves metabolic syndrome-exacerbated periodontitis in mice. International Journal of Molecular Sciences, 25(17), 9622.

[4] Xiao, J., Cai, T., Fang, Y., Liu, R., Flores, J. J., Wang, W., … & Tang, J. (2021). Activation of GPR40 attenuates neuroinflammation and improves neurological function via PAK4/CREB/KDM6B pathway in an experimental GMH rat model. Journal of Neuroinflammation, 18(1), 160.

[5] Fujita, T., Matsuoka, T., Honda, T., Kabashima, K., Hirata, T., & Narumiya, S. (2011). A GPR40 agonist GW9508 suppresses CCL5, CCL17, and CXCL10 induction in keratinocytes and attenuates cutaneous immune inflammation. Journal of Investigative Dermatology, 131(8), 1660-1667.

[6] Youm, Y. H., Gliniak, C., Zhang, Y., Dlugos, T., Scherer, P. E., & Dixit, V. D. (2025). Enhanced paracrine action of FGF21 in stromal cells delays thymic aging. Nature Aging, 5(4), 576-587.

Date Posted: July 15, 2026

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Forever Healthy Launches Evipedia AI Integration

Today, Forever Healthy announces the launch of a set of new tools to make it easier than ever for AI agents, research pipelines, and AI environments to integrate Evipedia.

Evipedia is Forever Healthy’s comprehensive, continuously updated online encyclopedia dedicated to providing much-needed, accurate, and up-to-date information on a wide range of health and longevity-related interventions.

The service is positioned as a backbone tool for the whole longevity and rejuvenation community. Forever Healthy actively encourages and supports its use in any way and on any project that helps people live longer, healthier lives. All content is licensed under CC BY 4.0.

Evipedia MCP Server

The Evipedia MCP server connects any client — Claude, Cursor, and others — straight to evipedia.ai. Agents can search reviews, pull a review’s conclusion, full Markdown, or structured medical metadata, and suggest new interventions.

GitHub: https://github.com/forever-healthy/evipedia-mcp

Evipedia Claude Plugin

The Evipedia plugin is the easiest way to get everything Evipedia into Claude — it wires in the MCP server plus a demo skill in a simple install.

GitHub: https://github.com/forever-healthy/fh-plugins

Agent-Friendly Site Policy

Evipedia places no barriers to automated access. Every agent and crawler is welcome, whether it’s an AI assistant (Grok, ChatGPT, Claude, Perplexity, and others) or a research tool. Each can fetch what it needs without special arrangements.

Agents start from the site’s https://evipedia.ai/llms.txt, a machine-readable, standardized signpost.

Structured Data on Every Review

Each review page now includes schema.org structured medical data in machine-readable format. It also lists the review’s primary-source citations as structured entries, so an agent can easily extract the evidence summary and its sources deterministically.

Keyless API

Easy to integrate Evipedia and all of its knowledge into your own projects. Stable URLs for linking, raw and structured formats for machines, and whole-catalog indexes. Plain HTTP GET — no keys, no SDK.

Automatic discovery for coding environments and agents via https://evipedia.ai/openapi.yaml.

What’s in Evipedia

600+ Evidence Reviews Evipedia covers a wide array of subjects, including first-generation rejuvenation therapies, peptides, supplements, botanicals, lifestyle protocols, and many more. The encyclopedia is constantly expanding its library and actively invites users to suggest new reviews.
A dual structure for every entry Each intervention has a one-page Quick Reference Sheet for at-a-glance protocol, benefits, risks, contraindications, and monitoring, plus a Full Evidence Review for in-depth analysis.
Continuous updates Entries are refreshed every 4-6 weeks to reflect new research, keeping reviews current rather than freezing them in time.
Stable, shareable permalinks Every intervention has a fixed, short URL and a purpose-designed social sharing card — ideal for citing a compound in a supplement stack or anchoring a claim in an online discussion.
Full Audit & Quality Transparency Every “Quick Reference Sheet” and “Evidence Review” on Evipedia is accompanied by its audit report, which outlines the detailed audit criteria and the history of audits and fixes applied to the documents.
AI & Agent-friendly, Extensive Integration Support Built as a backbone service for the longevity and rejuvenation community, Evipedia features a variety of integration tools and an easily accessible API. All free to use, under an AI and agent-friendly site policy and a Creative Commons 4.0 license.
Based on AI4L Evipedia is built on top of Forever Healthy’s open source AI4L framework, which enables anyone to create high-quality, evidence-based reviews of health and longevity interventions. At the core of AI4L is its novel “Audit-Driven Prompting” approach to generate hallucination-free, accurate, and well-structured reviews using frontier AI models.

About the Forever Healthy Foundation

The Forever Healthy Foundation gGmbH is a German nonprofit with a single mission: to enable people to extend their healthy lifespan and benefit from the rapidly approaching breakthroughs in human rejuvenation. More at forever-healthy.org.

Resources

Evipedia https://evipedia.ai
Evipedia – AI & Integration Tools https://evipedia.ai/integration
AI4L framework (GitHub) https://github.com/forever-healthy/AI4L
Forever Healthy Foundation https://forever-healthy.org
X @4ever_healthy

Press contact

hello@forever-healthy.org

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Date Posted: July 14, 2026

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Peripheral Inflammation May Drive Parkinson’s

A new study suggests that aging or Parkinson’s-triggering mutations create inflammation in peripheral tissues, and then circulating extracellular vesicles spread it to the brain, which might contribute to the disease [1].

Brain on fire

Nature made the brain remarkably well-protected, including from the elements by the skull and from pathogens by the blood-brain barrier (BBB). The brain was also long considered to be immune-privileged – that is, limiting local immune responses to reduce swelling and damage from inflammation; another example is the eye.

However, more recent studies have shown that some brain cells, particularly microglia, can act as immune cells, and brain inflammation exists and probably drives brain aging [2]. What has been largely unknown is whether systemic inflammation, such as inflammaging, affects brain inflammation, and if yes, what pathways are involved?

Chronic Inflammation

One well-characterized molecular engine of sterile inflammation is the cGAS-STING pathway, which senses DNA in the cell’s cytosol. Normally, it detects foreign DNA, such as from viruses and bacteria. The problem is, in aging and senescence, a cell’s own DNA – from a damaged nucleus or leaky mitochondria – can spill into the cytosol. cGAS can’t distinguish self from non-self and fires anyway, producing a smoldering, chronic interferon type I (IFN-I) response [3].

Exporting inflammation

A new study by an international collective of scientists, published in Cell Reports, asks whether cGAS-STING-driven systemic inflammation can be a factor in Parkinson’s disease, and what mechanisms might be involved. Leucine-rich repeat kinase 2 (LRRK2 in humans, Lrrk2 in mice) regulates the cell’s degradation and recycling machinery (endolysosomal system). The most common genetic cause of Parkinson’s is the G2019S mutation in the associated gene, which increases the enzyme’s activity. The authors refer to this gain-of-function mutation as LRRK2^GoF.

The authors’ central hypothesis is that LRRK2^GoF accelerates aging by degrading endolysosomal function, which causes self-DNA to accumulate in the cytosol, instead of being promptly recycled, and to be exported in DNA-carrying extracellular vesicles (EVs). Those EVs activate cGAS-STING not just in the original cell but also in distant cells – including, eventually, the brain.

First, the researchers took plasma and cerebrospinal fluid (CSF) samples from young healthy donors, aged healthy donors, and Parkinson’s patients. The latter showed elevated systemic IFN-I activity but not NF-κB activity, which belongs to a more general inflammation pathway.

At the cellular level, blood monocytes from Parkinson’s patients showed elevated IFNB1 transcripts, but an LRRK2 inhibitor normalized that IFNB1 elevation back to healthy levels, pointing to LRRK2’s causal involvement. However, the sample sizes in this and several other experiments were small (n=3-4).

To test causality, the team moved to a G2019S knock-in mouse model. Compared to controls, these Lrrk2^GoF mice had a markedly elevated, age-dependent IFN-I signature across plasma, monocytes, bone marrow, and spleen. RNA sequencing of spleen showed elevated inflammatory and senescence-associated gene expression.

The researchers then asked whether the brain also becomes inflamed and whether behavior is affected. In aged Lrrk2^GoF mice, neurons and microglia showed increased IFN-I and interferon-stimulated genes (ISGs) as well as a pronounced age-dependent motor decline. Importantly, the mutant mice also had increased BBB permeability and smaller brains. A leaky BBB might explain how peripheral inflammatory signals reach the brain.

Using RNA sequencing at different time points, the team found that the peripheral IFN-I signature was already present at 3 months, whereas the brain IFN-I signature and locomotor decline did not appear until 12 months. The author’s interpretation, crucial for the entire paper, is that inflammation starts peripherally and reaches the brain later.

The tiny Trojan horses

Mechanistically, IFN-I has triggers other than cGAS/STING. However, the researchers determined that eliminating those other triggers had no effect, while deleting STING completely reversed the elevated IFN-I response to wild-type levels in both splenocytes and microglia, reflecting changes in both a peripheral tissue and the brain. STING deletion also reduced microglial inflammation markers and protected the mice from the motor decline.

Lrrk2^GoF mice lost 51% of dopaminergic neurons with age, a major hallmark of Parkinson’s, versus about 30% in wild-type mice, and STING deletion prevented that loss. Changes in other neuronal populations were inconsistent.

Moving back in vitro to hunt for additional mechanistic insights, the authors showed that Lrrk2^GoF mouse fibroblasts reached senescence earlier than their wild-type counterparts and had elevated IFN-I activity, which could be normalized by inhibiting Lrrk2. Intriguingly, in transwell co-culturing (which blocks direct cell contact but allows diffusible/vesicular signals), senescent fibroblasts evoked a STING-dependent IFN-I response in physically separated macrophages.

Defective endolysosomal clearance is known to cause increased EV secretion, which is exactly what the researchers found in both Lrrk2^GoF and naturally aged fibroblasts. Again, this effect was abrogated by blocking Lrrk2. EVs taken from Lrrk2^GoF fibroblasts contained more genomic and mitochondrial DNA and induced STING-dependent IFN-I response in recipient macrophages.

The team then confirmed the EV mechanism in vivo and in humans. In Lrrk2^GoF mice, EV accumulation in plasma appeared early, but in the cerebrospinal fluid (CSF), it started much later, consistent with the “peripheral inflammation slowly causes brain inflammation” hypothesis. In humans, Parkinson’s patient macrophages showed reduced endolysosomal degradation. Plasma and CSF from Parkinson’s patients had more DNA-containing EVs, and EVs derived from these patients induced STING-dependent IFN-I, demonstrating a clean mouse-to-human bridge.

Yes I will donate❤️

Literature

[1] Öberg, M., Myers, C., Saffarzadeh, N., Maric, I., Murillo-León, M., Strömberg, A., … & Härtlova, A. (2026). STING-dependent peripheral inflammaging drives neurodegeneration via extracellular vesicles. Cell Reports, 45(7).

[2] Yin, F., Sancheti, H., Patil, I., & Cadenas, E. (2016). Energy metabolism and inflammation in brain aging and Alzheimer’s disease. Free Radical Biology and Medicine, 100, 108-122.

[3] Gulen, M. F., Samson, N., Keller, A., Schwabenland, M., Liu, C., Glück, S., … & Ablasser, A. (2023). cGAS–STING drives ageing-related inflammation and neurodegeneration. Nature, 620(7973), 374-380.

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News Nuggets

What is your personal story of getting into the longevity field?

Does that immense complexity ever frustrate you? Do you think we will understand enough to start reversing aging in the foreseeable future?

Or when IL-6 rises acutely in response to exercise, right?

Tell me if I understand this correctly: inflammatory fidelity is something like maintaining a healthy inflammatory homeostasis. We have a youthful blueprint in which the system is balanced, and with age, the harmful side begins to dominate. The idea is to bring it back to that more youthful state.

The inflammatory-fidelity work is still unpublished, but you recently posted a preprint on an inflammation-based epigenetic clock. Tell me more about it.

So, you went the opposite way – from the functionality.

OSKM validation is really interesting, but on the other hand it’s all epigenetic reprogramming. You could argue that the factors do something to the epigenome, including somehow recalibrating those genes – and that’s what you see in the readout.

Have you looked then at other validations, other therapies?

Did you test your inflammation-based clock against more established epigenetic clocks?

Did you find any organ-specific inflammatory signatures?

We usually focus on two sources of age-related inflammation: immune cells and senescent cells. You are suggesting that apparently non-senescent, non-immune cells can also participate actively in inflammatory signaling.

I also wanted to discuss your 2024 paper on age-associated clonal B cells. I have long been fascinated by clonal expansion, including CHIP, and its relationship to aging and malignancy. What did you find?

The implications may extend beyond individual diseases. I have a pet hypothesis that clonal immune aging could be a limiting factor in extreme longevity. Clonal expansions are common in centenarians and supercentenarians, and perhaps they help impose a ceiling on maximum lifespan.

Looking ahead, what is the roadmap for longevity therapies that target inflammation? In an optimistic, almost science-fiction scenario, how much could they affect human lifespan?

What are you personally planning to do to move the field in that direction?

Technical and biological reliability

A long-term clock can capture short-term effects instead

Ensuring reliability is difficult

Literature

How much regulation is too much?

The Montana way

Welcome aboard

Setting an example

When defenders just make things worse

Stopping NETs at their source

A receptor may be a target

Literature

A popular but misused coenzyme

The experts weigh in

Literature

An acute disease with lasting effects

Older mice are less poison resistant

Using TFEB to fight back

Literature

How do we measure aging?

Tick-tock

Limitations

Much work done, an exciting future ahead

Literature

Are trained muscles younger?

Training seems to partially protect against muscle aging

Reaction to acute exercise

Literature

Last year, we spoke about your path from software entrepreneurship into longevity and your goal of building a broader 2060 ecosystem. One year later, what has changed most in how you think about the mission?

What did you learn from the first 2060 Longevity Forum that shaped how you are approaching the 2026 edition?

Looking back at the 2025 Forum, what were the most concrete outcomes? Were there partnerships, investments, or projects that came directly from people meeting there?

Were there any parts of last year’s event that did not work as well as you hoped, or that you deliberately changed this time?

The 2026 Forum appears to be larger and more ambitious than the first edition. What is substantively different this year beyond having more speakers or attendees?

What did you learn from trying to bring scientists, startups, investors, clinicians, and policy advocates into the same room, and how has that shaped the 2026 program?

Longevity conferences can sometimes become echo chambers for people who already agree with each other. How are you trying to include disagreement, skepticism, or more critical perspectives?

After speaking with investors through the 2025 Forum and the 2060 Investment Club, what do you now think investors most misunderstand about longevity?

Since last year, the 2060 ecosystem seems to have expanded beyond the Forum itself, including the Investment Club, Ikare.Health, and newer investment initiatives. How do these pieces fit together?

Can you explain the 2060 Longevity Investment Club in practical terms? Who is it for, what role does it play, and how does it decide which startups or opportunities to present?

When your team evaluates a longevity startup, what does the diligence process actually look like? Who assesses the science, the market, and the investment risk?

Has your threshold for what counts as investable longevity science changed over the past year?

You have described longevity as a major investment opportunity, but biotech timelines are long and failure rates are high. How do you communicate the upside without encouraging unrealistic expectations?

You have also discussed newer investment concepts around broader exposure to longevity, including 3060.vc. What are you trying to build there, and what problem does it solve for investors?

Ikare.Health appears to focus on helping people act on today’s available longevity and preventive health tools. How do you distinguish responsible health optimization from overpromising or biohacking hype?

What evidence threshold do you personally use before you are comfortable recommending or building around a health intervention?

Since last year’s Forum, have you seen any concrete movement from policymakers, or is longevity still mostly being driven by private capital?

A recurring criticism of longevity is that it could become a field for wealthy early adopters. Given the high cost of conferences, clinics, and early-stage investment access, what does democratization mean in practice?

You have talked about building the South of France into a longevity hub. What parts of that are already real today, and what remains aspirational?

If we speak again next year, what would you want to be able to say 2060 accomplished in 2026?

Another look at exosomes

Fighting unwanted liver fat

Effects against senescence

Literature

Can we rejuvenate proteins?

Going enzyme-hunting

Evolution, weaponized

Moving to naturally glycated proteins