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 journalism and sustains our future.

Yes I will donate❤️

Date Posted: February 9, 2026

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Restoring the Strength of Natural Killer Cells

In Aging Cell, researchers have described why older natural killer (NK) cells lose their ability to eliminate harmful cells and a potential treatment for this decline.

Judgment and ability

At the cellular level, there is no due process. Natural killer (NK) cells judge other cells’ guilt or innocence by their surface proteins. They ruthlessly exterminate any foreign cells they find, which is what causes organ rejection; when they mistakenly attack the body’s own functional cells, autoimmune disorders are the result.

Even when uninfected and native to the body, cells can be guilty of two severe crimes: cancer and senescence. Encouraging NK cells to attack cancer despite its protections is a core part of modern oncology, and senescent cells are able to evade immune clearance as well [1].

However, errors in judgment are not the only potential issues with NK cells. This paper focuses on the armament of these cells, investigating the age-related reduction of their ability to do their jobs at all.

Older cells are much weaker

In their first experiment, the researchers derived NK cells from old groups of approximately 70-year-old humans and 700-day-old mice alongside young groups of approximately 21-year-old humans and 100-day-old mice. The human cells were tested against four groups of human dermal fibroblasts: three that had been driven senescent through toxicity, replication, or radiation, and a fourth that was derived from 75-year-old people; the mouse cells were tested against similar murine counterparts.

The results were entirely unsurprising. In every case, particularly against the naturally aged cells, the younger NK cells were far more effective in killing senescent fibroblasts than their older counterparts.

The differences were obvious even under a microscope. Young human NK cells were able to rapidly and tightly bind to senescent cells, killing them quickly, and then rapidly move on to the next senescent cell. Older NK cells failed at both; they were unable to form tight bonds, and they were lethargic in moving on to the next target.

Testing against various cancer cell lines yielded similar results. Older NK cells were less effective against multiple varieties of lymphoma and leukemia. Like their interactions with the senescent cells, this was found to be due to a lack of conjugation; the older NK cells were simply less able to bind with and properly destroy the cancer cells. An investigation into targeting mechanisms found that recognition of defective cells was not the reason why the older NK cells were less able to attack.

Instead, the older cells were found to have issues with their fundamental cytotoxic machinery. Normally, an NK cell will bind to a target cell and then attack it with a combination of perforin, which penetrates the cell, and granzyme B, which kills it. The attack itself requires granules of these weapons to be released in degranulation, and older NK cells were found to have both less binding ability and less degranulation than younger cells.

These reductions in ability were confirmed with a gene expression analysis. As expected, the older cells had downregulations in metabolism, activation, and core processes responsible for membrane transport and degranulation; the older cells were simply less able to bring their weapons to bear.

A potential solution

The researchers noted a key protein that was upregulated in their analysis: Cdc42, which has been noted to affect microtubular organization and increases with age. Previous work has found that Cdc42 has been implicated in the aging of hematopoietic stem cells (HSCs) [3], and proper microtubular organization is critical in correctly polarizing NKs and allowing cytotoxic granules to get to where they need to be.

A closer look at these cells’ microtubules suggested that this is likely to be the key issue. Older NK cells were significantly less organized than younger cells; in younger cells, Cdc42 sits on one side of the cell while tubulin sits on the other, but older cells did not have this polarity. Exposing older NK cells to CASIN, an inhibitor of Cdc42, was found to be successful in helping the older cells restore this balance.

Older NK cells exposed to CASIN received benefits in both conjugation and degranulation; in conjugation, the CASIN-exposed older cells even appeared to be slightly stronger than the younger ones. There were also benefits for mitochondria as well; older cells exposed to CASIN had even more of the energy transfer molecule ATP than their younger counterparts did, potentially further bolstering their overall ability.

However, CASIN did not give perfect results. While being substantially better than the unexposed older cells, the CASIN-treated older cells were not nearly as able to kill as many leukemic or senescent cells as younger cells were. Compared to untreated older and younger mice, CASIN-treated older mice were roughly halfway between those groups in their ability to remove senescent cells in the bone marrow and the spleen. CASIN was found to only affect the ability of NK cells and did not affect their proliferation.

These results, while substantially beneficial, were still only done in mice, and the potential side effects of using CASIN or another Cdc42 inhibitor in human beings have not been eludicated. The researchers suggest that further work should be done in exploring this approach as a treatment for age-related diseases that involve cancer or senescence.

Yes I will donate❤️

Literature

[1] Pereira, B. I., Devine, O. P., Vukmanovic-Stejic, M., Chambers, E. S., Subramanian, P., Patel, N., … & Akbar, A. N. (2019). Senescent cells evade immune clearance via HLA-E-mediated NK and CD8+ T cell inhibition. Nature communications, 10(1), 2387.

[2] Topham, N. J., & Hewitt, E. W. (2009). Natural killer cell cytotoxicity: how do they pull the trigger? Immunology, 128(1), 7-15.

[3] Florian, M. C., Dörr, K., Niebel, A., Daria, D., Schrezenmeier, H., Rojewski, M., … & Geiger, H. (2012). Cdc42 activity regulates hematopoietic stem cell aging and rejuvenation. Cell stem cell, 10(5), 520-530.

Date Posted: February 6, 2026

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First Human Cellular Reprogramming Trial Cleared by the FDA

Life Biosciences has announced that its trial of cellular reprogramming aimed at two age-related vision diseases has received a go-ahead from the FDA. We spoke with the company’s CSO to get more details.

Life Biosciences, the biotech company based on Harvard professor David Sinclair’s research into cellular reprogramming, stunned everyone last year by announcing that its clinical trial, the first-ever human trial of a reprogramming technology, will commence in the first quarter of 2026. A few days ago, the company cleared the last major hurdle on its way to this ambitious goal by receiving an Investigational New Drug (IND) clearance from the FDA to test the experimental drug ER-100 against optic neuropathies.

ER-100’s story begins with highly successful experiments in rodents, where Sinclair’s team used their own partial cellular reprogramming recipe to restore vision after a severe optic nerve injury, and then proceeded to a successful trial in non-human primates. This upcoming trial is focused on open-angle glaucoma (OAG) and non-arteritic anterior ischemic optic neuropathy (NAION), which is a “stroke of the eye” that can cause sudden blindness. Both diseases are age-related, with NAION being the most common acute optic neuropathy in adults over fifty.

Life Biosciences uses a proprietary reprogramming cocktail based on three out of four of the original Yamanaka factors: OCT-4, SOX-2, and KLF-4 (OSK). The company believes that this approach solves several problems that plagued early reprogramming research.

“It’s incredibly meaningful to see this science reach clinical testing after more than 30 years of work,” Sinclair said to Lifespan News. “I’m grateful to the many students, collaborators, and partners whose dedication helped bring these ideas from the lab to this milestone. For me personally, it’s deeply rewarding to see this work move into the clinic, with the potential to protect and restore vision for patients and to help unlock a new generation of therapies that target the diseases of aging across tissues.”

As this is the first reprogramming clinical trial, and one of the first longevity therapy clinical trials, many people in this industry view it as a seismic event. “This is a huge milestone for the entire partial reprogramming field, and it aligns with what we’ve seen as well: the FDA has been notably open and forward-thinking in how it engages with this approach,” said Yuri Deigin, CEO of YouthBio, which is developing its own anti-Alzheimer’s reprogramming-based therapy. “It’s also a strong signal for the broader longevity space that regulators are increasingly willing to evaluate therapies that aim to modify upstream epigenetic drivers of aging, rather than only treating downstream symptoms.”

We have long followed Life Biosciences and interviewed both David Sinclair and Life CSO Sharon Rosenzweig-Lipson. Following the FDA clearance announcement, we spoke with Sharon again to get her perspective on the trial timeline, Life Biosciences’ experience of interacting with the FDA, and the company’s future trajectory.

When are you planning to start the actual trial, and when can we expect results?

We’re in the final stages of getting our first site activated. We expect that to happen within a few weeks and to start enrolling patients right after that. By March, we’ll have begun enrolling patients.

And the ETA on results?

Because it’s a gene therapy, we’re going to enroll patient number one, wait 28 days, then enroll patients two and three, wait another 28 days. Then we’ll make decisions about going up and down on the dose. It’s going to take time to get through that, but we hope to have enough information by the end of the year on one or more doses. This will allow us to make decisions about whether we go to Phase 2 and start planning the next stage. We’re as eager as everybody else to move this as quickly as possible.

Usually, partial reprogramming involves pulsing with very carefully calculated doses so that the cells don’t undergo dedifferentiation. I understand that your therapy is “one-shot” – based on a single round of continuous administration.

I want to separate what we call partial reprogramming from what others do, which is transient reprogramming. Sometimes, you see transient reprogramming where you give it one or two days, wait a few more days in animals, then give it one or two more days. That’s often done with all four factors.

That’s not what we’re doing. We’re going to give doxycycline systemically – it’s an inducible system – keeping OSK on for an eight-week period. We have data showing that we can do it not just for two months, but for three months, or even beyond that in mice, demonstrating that we can achieve good reprogramming and good safety with a more continuous expression system.

Do you see at least some shift toward dedifferentiation with more time on the therapy?

We do not. What’s amazing about using OSK is that it’s not causing de-differentiation. It’s resetting the epigenetic code. That code, which made normal hearts, lungs, livers, retinal ganglion cells, gets degraded as we age or with age-related diseases. Our therapy resets that code back to a healthy, youthful state, but not all the way back, not to pluripotency. Cell identity is maintained.

It looks like you cracked one of the hardest problems in partial reprogramming by taking out the M out of the original four-factor Yamanaka cocktail.

Exactly. Taking the M out makes it impossible to go all the way back. You just can’t push the system hard enough.

What can you tell me about your interactions with the FDA? Was there something that pleasantly surprised you?

We met with the FDA almost two years ago to plan for our tox studies and make sure that they bought into what we were doing in a way that we could move it forward. We went through a series of questions and together with our recommendations and their recommendations, we outlined a path for our toxicology studies, distribution studies, and what they wanted to see us do clinically. We were very conscious of all the FDA guidance. Overall, we had a very smooth interaction with the FDA as it related to our IND clearance.

Since it’s the very first human trial of cellular reprogramming, you would think they would be extremely cautious to the point of seriously slowing you down, but you’re saying it was smooth sailing?

Our experience was very collaborative and positive. We have a lot of data that we walked into the room with supporting the safety profile. We had data in mice, data in non-human primates. We had our IND studies. We walked in with a lot of safety data, and I think that really helped.

Do you think this signals a broader change in the FDA’s attitude toward longevity therapies in general?

It’s hard for me to say. It’s a one-off, right? We haven’t put seven things through the FDA, so it’s hard to get a bigger picture of what this means for them. We’re pleased that for what we did, it was positively perceived and most importantly, we got to our “may proceed” letter without any major issues.

If we look past the indications you’re currently working with, what’s next for Life Biosciences?

We’ve already talked publicly about having nice data on reprogramming in the liver, which is quite exciting. We’re continuing to work on the liver, and you may see in the next few months a little more information on some other indications we’re working on. We’re excited that we’re continuing to achieve proof of concepts across a range of indications.

Yes I will donate❤️

Date Posted: February 5, 2026

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Increasing Senolytic Effectiveness by Stressing Mitochondria

Researchers publishing in Nature Aging have described how mitochondrial stress is a key part of why senolytics are effective.

Finding targeted effectiveness

Removing senescent cells with senolytics may reverse some aspects of aging.

What Are Senolytics? Senotherapeutics for Senescent Cells

Senolytics work by targeting one of several pro-survival pathways that senescent cells use to evade apoptosis and cling onto life. One of the challenges in dealing with senescent cells is that there are a number of different populations of these cells in our tissues and organs, each using different pro-survival pathways. It could be that multiple senolytic drugs need to be used to remove senescent cells using different pathways to survive.
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The researchers began this study by summarizing senescent cells and the senolytics created to eliminate them. They noted that few attempts have been made to determine which senolytics are the most broadly effective against senescent cells while having the least effects on non-senescent ones [1].

To that end, they created a senolytic specificity index (SSI), a simple metric that compares the number of senescent cells removed to the number of non-senescent cells removed. They tested 21 distinct agents, ranging from the well-known combination of dasatinib and quercetin (D+Q) to three different ABT compounds, one of which, ABT263 (Navitoclax), is well-known in the field as being an effective senolytic.

This researchers’ initial experiment confirmed that finding. Navitoclax was the most effective at selectively removing RPE-1 cells, which are human epithelial cells that are commonly used in senescence research; it was barely edged out in effectiveness by ARV825 at dealing with IMR-90, a line of human fibroblasts that serve the same purpose. Unfortunately, D+Q and fisetin performed very poorly on the SSI metric compared to these two compounds. Testing other types of senescent cells, and driving them senescent both replicatively and through toxin exposure, confirmed the broad effectiveness of both navitoclax and ARV825.

Some cells refuse to die

While these and similar compounds have advantages over other senolytics, such as not prompting suicidal apoptotic responses in non-senescent cells, they are not perfect. The researchers noted that previous work has found that BCL-2 inhibitors such as navitoclax are not effective against senescent preadipocytes [2] and that their own work has found imperfect clearance; roughly a quarter of the treated senescent cells survived navitoclax or ARV825, even after a week of senolytic treatment.

The researchers then took a step further, looking into why such strong senolytics failed against those particular cells. They found that the survivors had unusually high expressions of senescent cells’ characteristic SASP factors and that they fought more strongly against oxidative stress, decreasing the reactive oxygen species (ROS) that may have contributed to the other cells’ death.

Further analysis found that these cells were also better at clearing damaged mitochondria. One particular gene, ATP6V0E1, plays a key role in this process [3], and knocking this gene down greatly increased the effectiveness of navitoclax. The accumulation of damaged mitochondria is key to the effectiveness of both navitoclax and ARV825; cells with depleted mitochondria were significantly less likely to die to these senolytics.

Mitochondrial stress helps senolytics do their job

The researchers then experimented with various methods of imposing mitochondrial stress. First, they did so directly through gene silencing, finding that direct downregulation of mitochondrial maintenance functions causes senescent cells to die in the same way as when they are treated with these two senolytics. Directly interfering with mitochondrial DNA replication boosted their effects as well, and, critically, did not appear to kill off non-senescent cells.

The researchers switched cells from glycolysis to oxidative phosphorylation (OXPHOS) by reducing the amount of glucose that the cells received, simulating a low-carbohydrate diet and causing oxidative stress [4], but this had effects on normal cells as well as senescent ones. They then tested a GLUT1 inhibitor, BAY-876 [5], to force this shift; co-treating cells with BAY-876 along with navitoclax or ARV825 was found to increase the effectiveness of these senolytics while still sparing non-senescent cells from death.

These findings were replicated in mice. Older male mice were injected with melanoma cells that are known to co-locate with senescent cells, which fuel the growth of this cancer. Then, they were fed either navitoclax or ARV825 alongside either a normal or a low-carbohydrate ketogenic diet. The mice receiving the ketogenic diet had significantly stronger responses to senolytics; two key SASP factors that are known to attract this cancer were substantially reduced in the low-carb groups compared to the normal ones. While some previous work has linked ketogenic diets to cellular senescence [6], these researchers did not observe this in the lungs of their tested mice.

These findings are limited, and they present a conundrum to the field. The same basic stresses that prime senescent cells for removal by senolytics also affect how normal cells function. While these experiments showed benefits when stresses were combined with senolytics, it is still uncertain whether senolytics should be combined with physical interventions, such as low-carb diets or intensive exercise, for maximum effectiveness. Further work will need to be done on animals and people in order to determine if such combinations are helpful or harmful in the long run.

Yes I will donate❤️

Literature

[1] Di Micco, R., Krizhanovsky, V., Baker, D., & d’Adda di Fagagna, F. (2021). Cellular senescence in ageing: from mechanisms to therapeutic opportunities. Nature reviews Molecular cell biology, 22(2), 75-95.

[2] Zhu, Y. I., Tchkonia, T., Fuhrmann‐Stroissnigg, H., Dai, H. M., Ling, Y. Y., Stout, M. B., … & Kirkland, J. L. (2016). Identification of a novel senolytic agent, navitoclax, targeting the Bcl‐2 family of anti‐apoptotic factors. Aging cell, 15(3), 428-435.

[3] Colacurcio, D. J., & Nixon, R. A. (2016). Disorders of lysosomal acidification—The emerging role of v-ATPase in aging and neurodegenerative disease. Ageing research reviews, 32, 75-88.

[4] Liu, Y., Song, X. D., Liu, W., Zhang, T. Y., & Zuo, J. (2003). Glucose deprivation induces mitochondrial dysfunction and oxidative stress in PC12 cell line. Journal of cellular and molecular medicine, 7(1), 49-56.

[5] Siebeneicher, H., Cleve, A., Rehwinkel, H., Neuhaus, R., Heisler, I., Müller, T., … & Buchmann, B. (2016). Identification and optimization of the first highly selective GLUT1 inhibitor BAY‐876. ChemMedChem, 11(20), 2261-2271.

[6] Wei, S. J., Schell, J. R., Chocron, E. S., Varmazyad, M., Xu, G., Chen, W. H., … & Gius, D. (2024). Ketogenic diet induces p53-dependent cellular senescence in multiple organs. Science advances, 10(20), eado1463.

Date Posted: February 4, 2026

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Association Between Vitamins and Slower Biological Aging

A recent study analyzed data from over 15,000 participants and their intake of 11 vitamins, and the results suggested that higher vitamin intake, particularly of Vitamins C and B2, is associated with slower biological aging [1].

Beneficial molecules

One of the easiest and most accessible ways to improve health and lifespan is to consume a diet and supplements that provide adequate nutrition. Studies conducted in cell cultures and animals suggest that various vitamins, through their antioxidant and anti-inflammatory properties, have beneficial effects against aging processes [2, 3]. Human data suggest that vitamins have specific benefits, including improved lipid levels, better cognition and memory, reduced incidence of age-related macular degeneration, and lower mortality in cancer patients [4, 5, 6].

More granular approach

We recently covered a review that discussed the impact of multivitamins and minerals on health and longevity. That study analyzed the findings from 19 meta-analyses published in the last 25 years. While that study took a broad look at the impact of vitamins and minerals on different aspects of health, this study took a more granular approach and investigated the impact of 11 vitamins (A, B1, B2, B3, B6, B9, B12, C, D, E, and K), from both dietary and supplementary sources, on different aspects of biological aging. The authors used data from 15,050 participants, with a median age of 51 years, who were part of the nationally representative National Health and Nutrition Examination Survey (NHANES) between 2007 and 2018.

The authors used three methods to measure different aspects of biological aging: the Klemera-Doubal method biological age (KDM-BA), PhenoAge, and homeostatic dysregulation (HD), each using multiple different biomarkers to assess the speed of biological aging.

The choice of these aggregated measures of biological aging stems from limitations in previous studies, which often focus on single aging-related outcomes, whereas aging is a process that affects multiple systems. Therefore, measuring the speed of aging using aggregate measures of aging that incorporate multiple biomarkers is an attempt to reflect the complexity of the process.

All together and one-by-one

The epidemiological data on the relationship between vitamin intake and biological aging have limitations; for example, studies often focus on the impact of a single vitamin rather than a vitamin complex, which more accurately reflects reality. Those who investigate vitamins in combination often do not examine the effects of individual ingredients within the mixture. To address this gap, those researchers analyzed both scenarios.

An initial analysis, which divided participants into four quartiles by total vitamin intake, showed that those in the highest quartile were, on average, older, had higher socioeconomic status, and had healthier lifestyles. All three metrics of biological aging showed less accelerated aging in the highest quartile group than in those in the lowest quartile. After adjusting for multiple factors, the highest quartile still showed lower biological age acceleration, as measured by KDM-BA and PhenoAge; however, while there was a trend toward reduced age acceleration, the association was not statistically significant for HD.

The researchers also examined the effects of individual vitamins. Reduced biological aging was observed among individuals in the highest quartile for all vitamins, as measured by PhenoAge, but only for B2, B9, and C Vitamin intake, when measured by KDM. In contrast, analysis of HD didn’t show a significant impact of any vitamin.

Biological aging indicators agreed that among all vitamins tested, Vitamin C was the “primary protective driver.” B2, important for supporting metabolic and immune health, came in second. The researchers suggest that the potent role of Vitamin C might stem from its antioxidant effects, which protect against aging-related oxidative damage.

On the other hand, the results suggest that Vitamins B12 and D may have adverse effects. Vitamin B12 is important for blood and nerve cells health and helps make DNA. Vitamin D has many bodily functions, including calcium absorption in the gut; metabolism of calcium, phosphorus, and glucose; bone growth support, remodeling, and mineralization; reduction of inflammation; modulation of cell growth; and neuromuscular and immune function. The researchers suggest the adverse effects of Vitamin D may be due to the absence of a linear, dose-dependent relationship between Vitamin D intake and biological aging, in which higher doses accelerate aging, but this remains to be tested.

We have previously reported on the complex relationship between Vitamin D and the biology of aging. For example, while studies have linked Vitamin D supplementation to slower epigenetic aging, other research suggests that in some cases Vitamin D supplementation may not be beneficial, as a study published in Aging Cell suggests that administering Vitamin D to Alzheimer’s patients may actually make the problem worse.

Subgroup differences

The effects of vitamin intake were found to vary based on demographic and health characteristics. Males, people with a BMI under 30, current alcohol drinkers, people with lower education levels, people who ate less than 1500 calories a day, and people with comorbidities saw more beneficial effects. These results suggest that “individuals with higher underlying physiological stress or inflammation might derive greater benefit from adequate vitamin intake.”

When an analysis was conducted using only dietary data, the researchers obtained similar results: a protective effect of total dietary vitamin intake and a prominent role of Vitamin C in joint protective effects, highlighting the importance of obtaining vitamins through a healthy, whole-food diet.

Achieving nutritionally adequate levels

This study contributes to the growing body of evidence linking vitamin-rich diets to reduced biological aging. [7,8]. However, supplementation doesn’t have to imply taking excessive amounts, as the authors highlight that the “higher intake in our study primarily corresponds to achieving nutritionally adequate levels: over 90% of participants in the highest intake quartile met the Recommended Dietary Allowance for most vitamins.”

Yes I will donate❤️

Literature

[1] Zhang, X., Xu, Y., Wang, X., Chen, M., Xiong, J., & Cheng, G. (2026). Association between vitamin intake and biological aging: evidence from NHANES 2007-2018. The journal of nutrition, health & aging, 30(2), 100776. Advance online publication.

[2] Monacelli, F., Acquarone, E., Giannotti, C., Borghi, R., & Nencioni, A. (2017). Vitamin C, Aging and Alzheimer’s Disease. Nutrients, 9(7), 670.

[3] Kaźmierczak-Barańska, J., & Karwowski, B. T. (2024). The Protective Role of Vitamin K in Aging and Age-Related Diseases. Nutrients, 16(24), 4341.

[4] Seddon J. M. (2007). Multivitamin-multimineral supplements and eye disease: age-related macular degeneration and cataract. The American journal of clinical nutrition, 85(1), 304S–307S.

[5] Yeung, L. K., Alschuler, D. M., Wall, M., Luttmann-Gibson, H., Copeland, T., Hale, C., Sloan, R. P., Sesso, H. D., Manson, J. E., & Brickman, A. M. (2023). Multivitamin Supplementation Improves Memory in Older Adults: A Randomized Clinical Trial. The American journal of clinical nutrition, 118(1), 273–282.

[6] Harris, E., Macpherson, H., & Pipingas, A. (2015). Improved blood biomarkers but no cognitive effects from 16 weeks of multivitamin supplementation in healthy older adults. Nutrients, 7(5), 3796–3812.

[7] Canudas, S., Becerra-Tomás, N., Hernández-Alonso, P., Galié, S., Leung, C., Crous-Bou, M., De Vivo, I., Gao, Y., Gu, Y., Meinilä, J., Milte, C., García-Calzón, S., Marti, A., Boccardi, V., Ventura-Marra, M., & Salas-Salvadó, J. (2020). Mediterranean Diet and Telomere Length: A Systematic Review and Meta-Analysis. Advances in nutrition (Bethesda, Md.), 11(6), 1544–1554.

[8] Hu F. B. (2024). Diet strategies for promoting healthy aging and longevity: An epidemiological perspective. Journal of internal medicine, 295(4), 508–531.

Date Posted: February 3, 2026

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Weight Training Load Doesn’t Affect Muscle Mass or Strength

A new study suggests that, if sets are taken close to failure, the amount of weight on the bar does not determine muscle growth. However, individual differences in muscle-building ability appear to be real [1].

How should we train?

Muscle mass and strength are among the strongest predictors of longevity, but the best way to gain them is a matter of ongoing debate. In a study published in The Journal of Physiology, a team of scientists from McMaster University, with collaborators from Queen’s University and Liverpool John Moores University, set out to test the long-standing question of whether larger weights and fewer repetitions are superior to smaller weights and more repetitions for building muscle.

The scientists recruited 20 healthy, recreationally active but untrained young men and ran an ingeniously designed experiment: each participant trained both arms and both legs, but one arm and one leg were randomly assigned to high-load training (HL), and the other arm/leg did low-load training (LL).

HL was set at 8-12 repetitions at about 70%-80% 1RM (one-repetition maximum, the heaviest weight a person can lift for a single repetition with proper form). LL was set at 20-25 repetitions at about 30%-40% 1RM. Crucially, every set was taken to volitional fatigue, the inability to complete another repetition with good form (“close to failure”), so the overall effort was matched even though the weights differed. The baseline 1RM values were 18 ± 4 kg for bicep curls (about 40 pounds) and 40 ± 14 kg (almost 90 pounds) for knee extensions.

The weight is largely irrelevant

After 10 weeks of 3 supervised sessions per week, the researchers assessed muscle growth with several readouts: DXA to measure arm and leg lean mass, ultrasound to measure muscle cross-sectional area and thickness, and biopsies (from the vastus lateralis) to quantify type I and type II muscle-fiber growth. Muscle strength was also tested; in cohort studies, muscle strength often predicts mortality more strongly than muscle mass [2]. Across all these outcomes, the HL and LL conditions were statistically indistinguishable.

This does not mean, however, that all the participants performed at the same level. In fact, variability in responses between participants was quite high, even when accounting for baseline differences. In other words, some people were just better at gaining muscle mass and strength than others. The researchers tried to control for dietary differences, including by providing every participant with enough protein to support muscle gain. They hypothesize that this variability in individual muscle-building capacity stems mostly from intrinsic causes, such as genetic differences.

Complicating things even further, individual rankings for muscle mass gain and for muscle strength gain did not match. In other words, some participants were big “muscle size responders” without being big “strength responders,” and vice versa.

While it is tempting to interpret the results through the lens of total “volume load” (sets × reps × weight), this does not seem to cleanly reflect outcomes here, at least for bicep curls, in which HL produced a significantly higher volume load than LL, yet the hypertrophy readouts were still similar. This suggests that, under the study’s conditions (sets taken to volitional fatigue), volume load alone is not a reliable predictor of hypertrophy.

Muscle building gets slower with time

To probe the mechanism, the authors measured myofibrillar protein synthesis (MyoPS), the rate at which muscle builds new contractile proteins (actin and myosin). Because MyoPS was assessed on a time course (baseline, week 1, and week 10), they could report a clear dynamic: MyoPS rose early in training but was much smaller by week 10, signifying that it was attenuated with training, both in high-load and low-load limbs.

In contrast, the main hypertrophy and strength outcomes were measured only at two points: baseline and the end of week 10. Therefore, the study could compare net changes and HL/LL differences, but it could not determine whether those size/strength changes followed an “early spike then slowing” trajectory due to the lack of intermediate time points.

The authors suggest that early training may elevate MyoPS more due to novelty and muscle damage. Later, as the muscle adapts and damage decreases, the MyoPS response gets smaller even with progressive overload. Only vastus lateralis muscles (leg muscles), but not biceps, were biopsied, making a direct MyoPS comparison between arms and legs impossible.

While providing interesting and potentially actionable insights, the study also had limitations, including a small sample size, short duration, and possible “cross-education” effects (when training one limb affects the other), although such effects are thought to be minimal [3]. The study’s conclusions are also conditional on training to true fatigue, which is not trivial in real life.

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Literature

[1] Lees, M. J., Mcleod, J. C., Morton, R. W., Currier, B. S., Fliss, M. D., McKellar, S. R., … & Phillips, S. M. (2025). Resistance training load does not determine resistance training‐induced hypertrophy across upper and lower limbs in healthy young males The Journal of Physiology.

[2] Newman, A. B., Kupelian, V., Visser, M., Simonsick, E. M., Goodpaster, B. H., Kritchevsky, S. B., … & Harris, T. B. (2006). Strength, but not muscle mass, is associated with mortality in the health, aging and body composition study cohort. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 61(1), 72-77.

[3] Song, J. S., Yamada, Y., Kataoka, R., Hammert, W. B., Kang, A., Spitz, R. W., … & Loenneke, J. P. (2024). Does Unilateral High‐Load Resistance Training Influence Strength Change in the Contralateral Arm Also Undergoing High‐Load Training?candinavian Journal of Medicine & Science in Sports, 34(12), e14772.

Date Posted: February 2, 2026

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Life Biosciences Announces FDA Clearance of IND for ER-100

Life Biosciences, Inc., (“Life Bio”) a biotechnology company pioneering cellular rejuvenation therapies to reverse and prevent multiple diseases of aging, today announced that the U.S. Food and Drug Administration (FDA) has cleared its Investigational New Drug (IND) application for ER-100.

The IND clearance allows Life Bio to initiate a clinical program evaluating ER-100’s safety and potential to improve vision in patients with optic neuropathies. The Phase 1 first-in-human study (NCT07290244) will enroll individuals with open-angle glaucoma (OAG) and non-arteritic anterior ischemic optic neuropathy (NAION) to assess safety, tolerability, immune responses and impact on multiple visual assessments.

ER-100 originated from Life Bio’s Partial Epigenetic Reprogramming (PER) platform, which aims to restore aged or injured cells to a younger state by modifying the epigenome of cells, biochemical markers that regulate gene expression without altering the underlying DNA sequence. Life Bio’s approach allows for the controlled expression of three of the four Yamanaka factors, the transcription factors OCT-4, SOX-2, and KLF-4 (OSK), and has demonstrated safety and efficacy in multiple preclinical animal models by local injection into the eye (intravitreally). ER-100 is the first ever cellular rejuvenation therapy using epigenetic reprogramming to receive FDA clearance to enter human clinical trials.

“This important milestone in reaching the clinic is the result of years of research, optimization, and comprehensive nonhuman primate studies demonstrating controlled OSK expression, restoration of methylation patterns, and improved visual function, all of which has culminated in this IND clearance,” said Sharon Rosenzweig-Lipson, Ph.D., Chief Scientific Officer, Life Biosciences. “These results have paved the way for first-in-human evaluation of our cellular rejuvenation approach with the goal of improving the lives of people facing debilitating age-related disease, starting with optic neuropathies.”

About Optic Neuropathies

Optic neuropathies are a group of disorders characterized by the irreversible death of retinal ganglion cells (RGCs), the primary neurons connecting the eye to the brain. Because RGCs cannot naturally regenerate, their loss results in permanent vision impairment. Open-angle glaucoma (OAG) is a chronic neurodegenerative disease and a leading cause of blindness. While often associated with elevated intraocular pressure, RGC damage frequently continues despite treatment, and some patients suffer from OAG despite normal intraocular pressure. Non-arteritic anterior ischemic optic neuropathy (NAION), often termed “stroke of the eye,” is the most common acute optic neuropathy in adults over fifty. It involves sudden, painless vision loss due to insufficient blood flow, for which there are currently no approved treatments. Prevalence and incidence of both of these diseases rise with age, creating a growing global burden. Yet current standards of care fail to address the underlying neuronal degeneration, leaving a significant unmet medical need for disease-modifying therapies that can directly protect or regenerate RGCs to restore or preserve sight.

About Life Biosciences

Life Bio is a clinical-stage biotechnology company pioneering cellular rejuvenation therapies to reverse and prevent multiple diseases of aging. The company’s proprietary Partial Epigenetic Reprogramming (PER) platform utilizes three transcription factors—OCT4, SOX2, and KLF4—to restore older and damaged cells to a younger and healthier state. This innovative approach targets a root cause of aging at the epigenetic level, thereby offering the potential to address a wide range of serious age-related diseases. Life Bio’s lead program, ER-100, in development for optic neuropathies, including open-angle glaucoma (OAG) and non-arteritic anterior ischemic optic neuropathy (NAION), with a Phase 1 clinical trial initiated in the first quarter of 2026 for both indications. Beyond ER-100, the company is strategically broadening its therapeutic pipeline to address additional age-related diseases, underscoring the platform’s versatility and transformative potential. For more information, visit www.lifebiosciences.com or follow Life Bio on Twitter (X) and LinkedIn.

Media Contact

Jason Braco, PhD

LifeSci Communications

lifebio@lifescicomms.com

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Date Posted: February 2, 2026

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Rejuvenation Roundup January 2026

2026 has kicked off with several key research insights, and we’ve taken a look at the state of the industry and how rejuvenation biotechnology is moving forward. Here’s what’s been done in January.

Advocacy and Analysis

Longevity Biotech in 2025: The Expert Roundup: How did the year 2025 turn out for longevity biotech? Was it surprising or more of the same? Exciting or disappointing? Was the progress fast-moving or excruciatingly slow? What should we expect in 2026? We asked five leading experts to weigh in.

Geroscience in 2025: The Expert Roundup: 2025 was a good year for geroscience, marked by rapid strides and critical milestones. Yet, the path wasn’t always smooth: progress in some areas lagged, research hit dead ends, and familiar bottlenecks persisted.

Longevity Advocacy in 2025: The Expert Roundup: The last installment in our end-of-year series of expert roundups might be the least flashy, but it is arguably no less important than the previous ones dedicated to longevity biotech and geroscience.

Research Roundup

A Single Gut Microbe Suppresses Weight Gain in Mice: Scientists have found that a single microbial species can blunt the negative effects of a high-fat diet due to the unique mix of lipids it produces. They intend to identify its specific lipids in future work.

Recombinant Human Protein Stops Neuronal Loss in Alzheimer’s: A recent study investigated biomarkers that can help monitor trajectories of Alzheimer’s disease-related molecular processes, such as neuronal cell death, and how patients respond to treatments.

How Harmful Extracellular Vesicles Cause Brain Inflammation: In a paper published in Aging Cell, researchers have described how older cells send long interspersed nuclear element-1 (LINE-1) RNA to other cells in extracellular vesicles (EVs), spurring inflammation.

A Small Molecule Regenerates Cartilage in Aged Mice: By inhibiting the aging-related enzyme 15-PGDH, scientists have shifted cartilage cells towards a healthier phenotype, leading to a significant improvement in a mouse model of osteoarthritis.

A Protein That Exacerbates Heart Disease With Age: Researchers publishing in Aging Cell have found that Hevin, a protein found in the extracellular matrix that increases with age, leads to heart problems in older male mice.

The Geroprotective Potential of Hormone Replacement Therapy: A recent review of literature investigated the risks and benefits of hormone replacement therapy. The authors point out that this approach could be used as a geroprotector to extend the healthspan of women.

Vast Majority of Alzheimer’s Cases Attributable to One Gene: According to a new study, as many as 90% of Alzheimer’s cases can be attributed to “suboptimal” variants of the APOE gene. These results highlight the gene’s importance for Alzheimer’s prevention.

A New Look at How Blood Stem Cells Age: In Aging Cell, four Japanese researchers have recently described the aging of the hematopoietic system, which is responsible for the creation of blood.

Study Uncovers How Obesity Drives Chronic Inflammation: Scientists have discovered that obesity causes macrophages to ramp up mitochondrial DNA production, leading to more inflammation [1].

The Impact of Childbearing Trajectories on Aging: The authors of a recent study investigated the relationship between reproduction, aging, and survival. Two groups, women with the most live births and childless women, showed accelerated aging and increased mortality risk.

How Senescent Astrocytes Don’t Support Neurons: Resesarchers have found that thrombospondin-1 (TSP-1), a compound that is critical in growing brain synapses, is secreted by normal astrocytes but not senescent ones.

Exercise Variety Is Associated With Lower Mortality Risk: A new study links exercise variety, defined as regularly engaging in several types of physical activity, to significantly lower all-cause mortality. Exercise amount matters as well, but the effect plateaus quickly.

Using Placental Cells to Test Anti-Aging Compounds: Researchers publishing in Aging Cell have discovered that cells derived from the human placenta may be useful in estimating the effects of potential anti-aging treatments.

Rapamycin Protects Immune Cells by Reducing DNA Damage: A new study from the Universities of Oxford and Nottingham has uncovered a potential new mechanism by which rapamycin counters immunosenescence. Rather than increasing autophagy or reducing protein synthesis, the effect appears to involve directly reducing DNA damage burden in immune cells.

Shingles Vaccination Is Associated With Slower Aging: An analysis of over 3800 older adults found that shingles vaccination is associated with lower inflammation scores, slower epigenetic and transcriptomic aging, and a lower composite biological aging score.

Engineered Extracellular Vesicles Reduce Arrhythmia in Rats: In Nature Communications, researchers have described how small extracellular vesicles (sEVs) fused with plasma membrane proteins successfully treated heart arrhythmia in a rat model.

CRISPR-Based Screen Reveals Possible Anti-Tau Mechanism: Using an ingenious CRISPR-based screening technique, scientists have found a protein that tags tau for degradation and is more strongly expressed in tau-resilient neurons.

Minimum combined sleep, physical activity, and nutrition variations associated with lifeSPAN and healthSPAN improvements: Modest concurrent improvements in sleep, physical activity, and diet were associated with meaningful gains in lifespan and healthspan.

Optimal type and dose of exercise to improve cognitive function in healthy and pre-sarcopenic older adults: Exercise is a scalable, safe, and clinically effective approach for preserving late-life cognition. For healthy older adults, aerobic or resistance training at ≥600 MET·min/week is recommended; for pre-sarcopenic individuals, multimodal programs at approximately 700–800 MET·min/week offer the best balance of efficacy and sustainability.

Exploring the physiological limits of aging: a case study of the male 50-km world record in the 80+ age category: The exceptional endurance performance of this master athlete was attributed to his well-preserved VO2max. Analyses on the limiting factors to VO2max suggest that his exceptional performance was mostly due to the final steps of the oxygen cascade.

Epigenetic age deceleration reflects exercise-induced cardiorespiratory fitness improvements: This study supports the use of GrimAge in evaluating longevity interventions and highlights the importance of accounting for leukocyte composition in epigenetic aging research.

High-protein diet promotes aging by activating the CG6415/AMT gene and disrupting mitochondrial homeostasis: This is partly via activation of the CG6415/AMT gene and subsequent disruption of mitochondrial homeostasis. Isoleucine plays a relatively key role in this process.

The effects of magnesium L-threonate (Magtein®) on cognitive performance and sleep quality in adults: a randomised, double-blind, placebo-controlled trial: The results from this study suggest Magtein® supplementation for 6 weeks improves overall cognition, cognitive age, working memory, reaction time, HR, HRV, and some subjective, but not objective measures of sleep in healthy adults with self-reported dissatisfied sleep.

Whey Protein Supplementation Positively Modulates Lung Function and Pulmonary and Systemic Immune Response in Older Adults: IWPS improved pulmonary and systemic immune response, lung function and functional capacity of older adults.

Association between vitamin intake and biological aging: evidence from NHANES 2007–2018: Higher intake of dietary vitamin mixture was associated with slower biological aging, with vitamin C as the key protective driver. These findings support recommending vitamin-rich diets to promote healthy aging.

Metabolomic sweet spot clock predicts mortality and age-related diseases in the Canadian Longitudinal Study on Aging: The Sweet Spot Clock provides a reproducible and interpretable measure of biological age. By modeling deviations from optimal metabolite levels and training on health status rather than age, it offers a tool for understanding aging heterogeneity and identifying individuals at risk of health decline.

Heritability of intrinsic human life span is about 50% when confounding factors are addressed: When extrinsic mortality is accounted for, estimates of heritability of life span due to intrinsic mortality rise to about 55%, more than doubling previous estimates.

Microbiota from young mice restore the function of aged ISCs: Elevated levels of Akkermansia muciniphila in aged mice cause an attenuation of Wnt signaling and reduced regenerative function of aged ISCs in vivo. Aging-associated changes in the microbiota can thus be causatively linked to a reduced function of aged ISCs.

Oral Delivery of R-spondin1-Loaded Small Extracellular Vesicles Activates WNT Signalling Pathway to Accelerate Intestinal Injury Repair and Reverse Ageing: Collectively, this study establishes evRSPO1 as a potential first-in-class, orally deliverable therapeutic that overcomes biological barriers to activate ISCs, enabling efficient intestinal tissue repair and rejuvenation.

Intermittent hypobaric pressure induces selective senescent cell death and alleviates age-related osteoporosis: This study reveals a previously unknown role of HP as a natural senolytic to eliminate senescent cells, and identifies TMEM59 as a new HP-activated ion channel protein.

Comparative analysis of senolytic drugs reveals mitochondrial determinants of efficacy and resistance: These findings suggest that mitochondrial quality control is a key determinant of resistance to ABT263-induced and ARV825-induced senolysis, providing a possible framework for rational combination senotherapies.

IGF2BP3-dependent glutamine/BCAA metabolic rewiring rejuvenates aged human adipose-derived stem cells for enhanced tissue regeneration: This study proposed two therapeutic strategies: nutrient supplementation to rescue metabolic deficits and m6A modulation to stabilize key mRNAs, providing a clinically feasible protocol to optimize elderly-derived hASCs for tissue regeneration.

Systematic identification of single transcription factor perturbations that drive cellular and tissue rejuvenation: These results suggest a shared set of molecular requirements for cellular and tissue rejuvenation across species.

How and why does aging occur? Updating evolutionary theory to meet a new era of data: The researchers provide an overview of existing models that address heterogeneity and outline future directions and applications that would advance this key area in aging and biomedical research.

The Longevity Medicine Patient Experience Framework: A Seven-Domain Model for Optimizing Person-Centered Longevity Medicine: By operationalizing a patient-experienced, person-centered approach, this framework offers potential solutions to common challenges in longevity medicine, including care fragmentation, accessibility barriers, and poor patient engagement.

Coming Up

The Longevity World Forum Confirms Madrid for 2026: The Longevity World Forum announces its move to Madrid, reinforcing its international positioning with a new location aligned with its growth and leadership objectives in the field of longevity science and healthy aging.

Rejuve.AI Launches International Longevity Research Database: Rejuve.AI is activating the International Longevity Research Database (IRLDB) through its first real-world study cohort at the Longevity Biomarkers Competition and Summit, taking place February to March 2026 as part of the Infinite Games in Roatán, Honduras.

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Date Posted: January 30, 2026

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CRISPR-Based Screen Reveals Possible Anti-Tau Mechanism

Using an ingenious CRISPR-based screening technique, scientists have found a protein that tags tau for degradation and is more strongly expressed in tau-resilient neurons [1].

Some neurons are more equal than others

The accumulation of tau protein fibrils in neurons is a hallmark of Alzheimer’s and several other diseases [2]. Scientists have long noticed that even in the brains of people who died of Alzheimer’s, some neurons are markedly healthier than others, suggesting that neurons differ in how they handle tau and that these differences may explain selective vulnerability in tauopathies [3].

In a new study published in the journal Cell, scientists from the University of California San Francisco built a human-neuron CRISPR interference (CRISPRi) screening platform and asked, genome-wide, which genes push tau toward or away from oligomer accumulation. Tau oligomers, which consist of chains of several tau molecules, are considered a crucial step in the formation of tau fibrils.

Full-genome screening

The team compared isogenic iPSC-derived neurons with or without a familial tauopathy mutation (V337M) in the gene MAPT. Using the oligomer-selective antibody T22, they found elevated tau oligomer levels in the mutated neurons. The signal dropped with MAPT knockdown, showing that the assay depends on tau expression and can report genetically driven changes.

The researchers used a genome-wide CRISPR “turn-down” screen in human neurons to find genes that control tau oligomers – without having to test 20,000 genes one by one. Essentially, they washed the cells in a cocktail of viral vectors, each one carrying a CRISPR-based construct to silence a particular gene. The concentration was such that the vast majority of cells received only one vector or none at all, creating a variety of cells with one different gene turned down.

The researchers then stained the neurons with T22, an antibody that recognizes tau oligomers, and used flow cytometry to sort cells into low-oligomer and high-oligomer bins. They then sequenced the CRISPR guide RNAs present in each bin to see which genes were knocked down.

This produced a ranked list of candidate genes, which the authors stress-tested in follow-up screens. One gene in particular, CUL5 – part of the ubiquitin-proteasome machinery that tags proteins for degradation – was a top hit across these different screens, making it a natural focus for a deeper mechanistic analysis.

CUL-ling tau

Because CUL5 is a key component of an E3 ubiquitin ligase, which is part of the cellular machinery that tags specific proteins for proteasomal destruction, the authors suspected that altering CUL5 would change how efficiently neurons can clear tau. To test this, they used individual CRISPRi guides to dial down CUL5 and RNF7, its core partner, and then directly measured tau.

The team found that tau levels rose when this ligase machinery was impaired. They then showed that the effect was post-translational, meaning that, with CUL5 knocked down, tau was becoming more stable, not just more expressed. Blocking the proteasome eliminated the CUL5-linked difference, tying the pathway to proteasomal clearance. Finally, they found the specific region of tau (around residues 80-130) that the ligase complex uses to target it for disposal.

In multiple human single-cell datasets, higher expression of CUL5 and key complex members was linked to neuronal resilience in Alzheimer’s disease and other tauopathies, suggesting that stronger CUL5-based ubiquitin-proteasome capacity may help certain neuron populations better withstand tau stress.

“CUL5 is uniquely suited to getting rid of tau,” said Martin Kampmann, Ph.D., professor of Biochemistry and Biophysics at UCSF. “Maybe a future therapy could enhance the body’s natural mechanism for avoiding neurodegeneration. It’s the first time we’ve been able to screen human neurons for genes that determine their resilience to tau. We hope that CUL5 can be the first of many new targets for drug discovery against dementias.”

Mitochondrial function flagged, too

A separate signal from the same CRISPRi screens also demanded attention: beyond the CUL5 “tau clearance” pathway, the strongest pathway-level hits pointed to mitochondrial oxidative phosphorylation/ETC (electron transport chain) genes as major modifiers of tau-oligomer burden.

The authors pivoted to ask what mitochondrial dysfunction does to tau. Using drugs that inhibit the ETC (notably rotenone and antimycin A), they caused tau levels to rise. Moreover, neurons started producing a form of tau that resembles what Alzheimer’s biomarker tests are designed to detect.

They traced this effect to oxidative stress (ROS) rather than generic energy failure: ROS increased alongside fragment formation, adding hydrogen peroxide to generate ROS could reproduce the effect, and antioxidants blunted it. While the role of mitochondrial dysfunction in dementias is known, this study provides more details that may be relevant for future therapies.

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Literature

[1] Samelson, A. J., Ariqat, N., McKetney, J., Rohanitazangi, G., Parra Bravo, C., Bose, R. S., Travaglini, K. J., Lam, V. L., Goodness, D., Ta, T., Dixon, G., Marzette, E., Jin, J., Tian, R., Tse, E., Abskharon, R., Pan, H. S., Carroll, E. C., Lawrence, R. E., … Kampmann, M. (2025). CRISPR screens in iPSC-derived neurons reveal principles of tau proteostasis. Cell.

[2] Serrano-Pozo, A., Frosch, M. P., Masliah, E., & Hyman, B. T. (2011). Neuropathological alterations in Alzheimer disease. Cold Spring Harbor perspectives in medicine, 1(1), a006189.

[3] Roussarie, J. P., Yao, V., Rodriguez-Rodriguez, P., Oughtred, R., Rust, J., Plautz, Z., … & Greengard, P. (2020). Selective neuronal vulnerability in Alzheimer’s disease: a network-based analysis. Neuron, 107(5), 821-835.

Date Posted: January 29, 2026

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Rejuve.AI Launches International Longevity Research Database

Roatán, Honduras — Rejuve.AI is activating the International Longevity Research Database (IRLDB) through its first real-world study cohort at the Longevity Biomarkers Competition and Summit, taking place February to March 2026 as part of the Infinite Games in Roatán, Honduras.

The IRLDB is being activated through its first registered, consented cohort. Participants enrolled in the Longevity Biomarkers Competition are pre-boarded into the database under a formally registered IRLDB protocol. They contribute standardized baseline and follow-up biomarker data alongside continuous, app-mediated real-world tracking using the Rejuve Longevity App,

This cohort represents an early deployment of Rejuve.AI’s research infrastructure, ahead of a broader public rollout planned as on-chain and scaling components are introduced to support larger study volumes.

In parallel, Infinita City will host the next installment of the JoyScore experiment in collaboration with Longevity Rave, following a pilot conducted at Frontier Tower in December 2025.

A Real-World, App-Enabled Longevity Study

The Longevity Biomarkers Competition functions as the first live application of the IRLDB protocol, demonstrating how longevity research can be conducted in real-world settings while maintaining scientific rigor.

Participants undergo standardized testing at defined timepoints while contributing longitudinal data via the Rejuve App between assessments. Measurements include blood-based biomarkers, epigenetic clocks, metabolomic profiles, wearable-derived physiological data, and structured questionnaires capturing function, behavior, and environment.

This approach enables consistent benchmarking while preserving ecological validity, capturing how individuals actually live, train, and adapt over time. It also provides a structured framework for self-experimentation that prioritizes data quality, participant safety, and informed consent.

Mapping the Signatures of Human Longevity Summit

The competition is preceded by an opening summit on February 7–8, bringing together leading figures in aging research, clinical longevity, and translational science, including Eric Verdin, Andrea Maier, and other international researchers and practitioners, with participation from organizations including XPRIZE, the Buck Institute for Research on Aging, and the Biomarkers of Aging Consortium.

A central focus of the summit is the ongoing debate in the longevity field around healthspan versus lifespan as the primary goal of intervention. Discussions explore the premise that meaningful lifespan extension necessarily implies preserved or improved healthspan, and that regenerative and damage-repair approaches should not extend periods of decline.

Additional themes include how emerging and partially unvalidated therapies are being used in practice, and how clinics, consumers, and researchers can approach such interventions in ways that maximize learning, data sharing, safety, and participant autonomy.

JoyScore Part II and the Exposome

The summit also incorporates the second installment of the JoyScore experiment, led by longevity researcher Tina Woods. JoyScore explores how psychological wellbeing, social connection, and environmental and lifestyle exposures interact with biological aging processes over time.

Attendees of the Infinita Games may opt in to participate, contributing JoyScore data through the Rejuve App. This enables psychosocial and exposomic signals to be analyzed alongside biomarker and functional data within the same research infrastructure.

About Rejuve.AI

Rejuve.AI is a decentralized longevity research network developing open, protocol-driven systems for studying aging, healthspan, and potential rejuvenation through real-world, longitudinal data.

About Infinita City

Infinita City is a longevity-focused innovation environment in Prospera, Roatán, supporting real-world experimentation in health, science, and emerging technologies.

About Longevity Rave

Longevity Rave is a global platform exploring longevity through science, culture, and participatory experiences, including the JoyScore experiment.

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Date Posted: January 29, 2026

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Engineered Extracellular Vesicles Reduce Arrhythmia in Rats

In Nature Communications, researchers have described how small extracellular vesicles (sEVs) fused with plasma membrane proteins successfully treated heart arrhythmia in a rat model.

Why do people need pacemakers?

In a healthy heart, the sinoatrial node (SAN) serves as a natural regulator, commanding the heart to regularly contract. As it becomes dysfunctional and fibrotic with age, heart arrhythmia is the result [1]. Artificial pacemakers are the standard of care for this condition, but such devices come with their own complications [2].

Some work has focused on regenerating the SAN, including turning heart cells into pacemaker cells with gene therapy [3], directly injecting SAN cells created through induced pluripotency [4], and, in some cases, targeting specific ion channels through RNA editing [5]. However, there are inherent risks of cancer and cellular death, and making these interventions into safe, reliable, and broadly applicable therapies has proven to be difficult [6].

An effective delivery method

These researchers, therefore, turned to sEVs as their desired method for bringing protective RNA and proteins to the cells that need them. Ordinary sEVs, however, are quickly recycled in the body and do not naturally target specific cells [7]. Engineering these vesicles, therefore, has become a priority, with multiple techniques being explored [8]. Coating them in platelet membrane proteins serves two key functions: it hides them from the immune system, and it encourages delivery to injured areas [9].

The particular sEVs used in this experiment were derived from human induced pluripotent stem cells (hiPSCs), filtered by size. Rat platelets were then stripped of their contents and their membranes were attached to the sEVs, creating PM@i-sEVs. The researchers then subjected these modified sEVs to a barrage of tests, confirming that the plasma membrane was securely fastened to the sEV and that the membrane-enclosed sEVs do not congeal together the way that actual platelets do.

PM@i-sEVs were confirmed to be taken up into induced cardiomyocytes (iCMs). 24 hours after they were taken up, they released their contents into the cells’ cytosol. Further testing in rats found that they were found to be better taken up by SAN cells instead of being concentrated in the liver the way that unmodified sEVs are. Further in vitro testing found that they were significantly more attracted to collagen-coated cells than their unmodified counterparts.

Effective in rats

To test the effectiveness of PM@i-sEVs, the researchers created a rat model of heart arrhythmia. The rats’ SANs were injured with sodium hydroxide and ischemia-reperfusion, which was confirmed to induce arrhythmia.

24 andd 72 hours after this injury, some of these rats were injected with PM@i-sEVs, others were injected with i-SEVs, and others served as controls. After a month, the rats treated with PM@i-sEVs fared much better than the other two groups as measured by multiple metrics of heart rhythm function, and there was no damage to other organs as a result of this treatment.

A closer examination found that the treated rats had SANs that were visibly less diseased than those of the other two groups. There was less fibrosis, better collagen deposition, more organized tissue structure, and less congestion; further in vitro experiments found that PM@i-sEVs do indeed significantly reduce fibrosis in cells.

An examination of the specific microRNA molecules found in the sEV payloads suggested potential reasons why. Several of these molecules that were “previously linked to cardiac repair, arrhythmia suppression, and ischemic preconditioning” were found in these vesicles. While this was only an injured rat model and further work needs to be done to confirm these EVs’ effects in naturally aged organisms, including humans, this approach appears to be promising.

Yes I will donate❤️

Literature

[1] Duan, S., & Du, J. (2023). Sinus node dysfunction and atrial fibrillation—Relationships, clinical phenotypes, new mechanisms, and treatment approaches. Ageing Research Reviews, 86, 101890.

[2] Glikson, M., Nielsen, J. C., Kronborg, M. B., Michowitz, Y., Auricchio, A., Barbash, I. M., … & Witte, K. K. (2022). 2021 ESC Guidelines on cardiac pacing and cardiac resynchronization therapy: Developed by the Task Force on cardiac pacing and cardiac resynchronization therapy of the European Society of Cardiology (ESC) With the special contribution of the European Heart Rhythm Association (EHRA). EP Europace, 24(1), 71-164.

[3] Kapoor, N., Liang, W., Marbán, E., & Cho, H. C. (2013). Direct conversion of quiescent cardiomyocytes to pacemaker cells by expression of Tbx18. Nature biotechnology, 31(1), 54-62.

[4] Protze, S. I., Liu, J., Nussinovitch, U., Ohana, L., Backx, P. H., Gepstein, L., & Keller, G. M. (2017). Sinoatrial node cardiomyocytes derived from human pluripotent cells function as a biological pacemaker. Nature biotechnology, 35(1), 56-68.

[5] D’Souza, A., Pearman, C. M., Wang, Y., Nakao, S., Logantha, S. J. R., Cox, C., … & Boyett, M. R. (2017). Targeting miR-423-5p reverses exercise training–induced HCN4 channel remodeling and sinus bradycardia. Circulation research, 121(9), 1058-1068.

[6] Vo, Q. D., Nakamura, K., Saito, Y., Iida, T., Yoshida, M., Amioka, N., … & Yuasa, S. (2024). IPSC-derived biological pacemaker—From bench to bedside. Cells, 13(24), 2045.

[7] Rai, A., Claridge, B., Lozano, J., & Greening, D. W. (2024). The discovery of extracellular vesicles and their emergence as a next-generation therapy. Circulation research, 135(1), 198-221.

[8] Fan, M., Zhang, X., Liu, H., Li, L., Wang, F., Luo, L., … & Li, Z. (2024). Reversing Immune Checkpoint Inhibitor–Associated Cardiotoxicity via Bioorthogonal Metabolic Engineering–Driven Extracellular Vesicle Redirecting. Advanced Materials, 36(45), 2412340.

[9] Hu, C. M. J., Fang, R. H., Wang, K. C., Luk, B. T., Thamphiwatana, S., Dehaini, D., … & Zhang, L. (2015). Nanoparticle biointerfacing by platelet membrane cloaking. Nature, 526(7571), 118-121.

Date Posted: January 28, 2026

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Shingles Vaccination Is Associated With Slower Aging

An analysis of over 3800 older adults found that shingles vaccination is associated with lower inflammation scores, slower epigenetic and transcriptomic aging, and a lower composite biological aging score [1].

Beneficial side effects

Vaccines are developed to prevent specific diseases, such as polio, measles, hepatitis, and many others. However, recent data suggest that some adult vaccines may have unintended yet beneficial effects. For example, vaccines against herpes zoster (shingles), influenza, and pneumococcus were linked to reductions in the risk of age-related diseases, such as dementia and cardiovascular diseases [2, 3, 4].

This initial data sparked the interest of other researchers, including the authors of this study, to investigate this topic further. The study’s authors specifically focused on the shingles vaccine, which protects against a viral infection caused by the reactivation of the chickenpox virus.

The researchers used data from the nationally representative U.S. Health and Retirement Study of 3,884 adults 70 years old and up in order to address the impact of shingles vaccination (specifically an earlier version called Zostavax) on seven biological aging domains: inflammation, innate and adaptive immunity, blood flow forces (cardiovascular hemodynamics), neurodegeneration, and epigenetic and transcriptomic aging that affect gene expression.

Vaccinating against aging

Analysis of the data, after adjusting for demographic, socioeconomic, and health-related factors, showed significant associations between shingles vaccination and three of the seven biological aging domains: lower inflammation scores and slower epigenetic and transcriptomic aging.

The lower observed inflammation scores suggest reduced chronic inflammation. In the elderly, chronic inflammation, often referred to as “inflammaging,” contributes to multiple age-related conditions such as heart disease, frailty, and cognitive decline.

“By helping to reduce this background inflammation — possibly by preventing reactivation of the virus that causes shingles, the vaccine may play a role in supporting healthier aging,” said Research Associate Professor of Gerontology Jung Ki Kim, the study’s first author. “While the exact biological mechanisms remain to be understood, the potential for vaccination to reduce inflammation makes it a promising addition to broader strategies aimed at promoting resilience and slowing age-related decline.”

Beyond inflammation, gene expression and epigenetic profiles were also positively affected by vaccination. Epigenetic age acceleration was assessed using DNA methylation-based aging clocks, which are used to measure biological age, assess the rate of aging, and evaluate the risk of various health outcomes, including mortality, frailty, and chronic diseases.

Since aging affects multiple systems in the body, the researchers created a composite biological aging score by integrating information across six domains into a single measurement; the adaptive immunity domain was excluded due to unexpected results, which could have obscured meaningful effects. Shingles vaccination was associated with a lower composite biological aging score, suggesting that this vaccine affects multiple bodily systems.

Overall, “This study adds to emerging evidence that vaccines could play a role in promoting healthy aging by modulating biological systems beyond infection prevention,” said Kim.

Unexpected results

However, not all measured components showed improvements. The authors reported that, contrary to their expectations, vaccination was associated with higher adaptive immunity scores, reflecting poorer adaptive immune function. This was difficult to interpret, and the lack of additional biomarkers prevented the researchers from testing some of their hypothesized explanations. They also suggest the possibility that vaccination might simultaneously have protective and potentially adverse effects.

The lack of effect of the shingles vaccine on neurodegeneration biomarkers was also rather surprising, given previous links between shingles vaccination and reduced dementia incidence. However, the researchers believe that the biomarkers they used, which reflect long-term damage, might not capture the direct effect of the vaccination on dementia; instead, the effect might be indirect, such as through reduced inflammation, which is more dynamic.

The long-term effects

While vaccination is a one-time intervention, it may have long-term effects. An analysis of the impact of vaccination over time shows that reduced epigenetic and transcriptomic aging, as well as composite biological aging scores, are present in peopple who had recently received the vaccine and in people who had received it 4 or more years earlier. While the persistence of epigenetic and gene expression effects suggests a potential for long-term effects, those effects may diminish over time, since both DNA methylation and gene expression changes were greater in people vaccinated more recently. However, this needs further investigation.

Regarding different domains of aging, the initial three years post-vaccination were not associated with changes in other measured domains. However, three or more years after vaccination, the researchers observed an association with lower inflammation and innate immunity scores, but poorer adaptive immune function. The researchers point out that these observations might suggest that the impact of the shingles vaccine on the immune system and inflammatory responses unfolds slowly over time, thereby impacting the immune system in the long term.

Beyond preventing illnesses

“These findings indicate that shingles vaccination influences key domains linked to the aging process,” said study coauthor Eileen Crimmins, USC University Professor and AARP Professor of Gerontology. “While further research is needed to replicate and extend these findings, especially using longitudinal and experimental designs, our study adds to a growing body of work suggesting that vaccines may play a role in healthy aging strategies beyond solely preventing acute illness.”

This is promising, especially since this intervention was effective even in the older population (people studied here were over 60 when they received the vaccine), who are usually less responsive to interventions. However, it remains to be determined whether stronger effects would be observed if a younger population (in their 50s) were to receive the vaccine or if participants received a newer formulation of the shingles vaccine (Shingrix).

This study also raises a very important question of whether interventions not designed to target aging have geroprotective effects. If so, some of them, such as the shingles vaccine, might be low-cost interventions with the potential to positively influence biological aging and extend healthspan.

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Literature

[1] Kim, J. K., & Crimmins, E. M. (2026). Association between shingles vaccination and slower biological aging: Evidence from a U.S. population-based cohort study. The journals of gerontology. Series A, Biological sciences and medical sciences, glag008. Advance online publication.

[2] Shah, S., Dahal, K., Thapa, S., Subedi, P., Paudel, B. S., Chand, S., Salem, A., Lammle, M., Sah, R., & Krsak, M. (2024). Herpes zoster vaccination and the risk of dementia: A systematic review and meta-analysis. Brain and behavior, 14(2), e3415.

[3] Bukhbinder, A. S., Ling, Y., Hasan, O., Jiang, X., Kim, Y., Phelps, K. N., Schmandt, R. E., Amran, A., Coburn, R., Ramesh, S., Xiao, Q., & Schulz, P. E. (2022). Risk of Alzheimer’s Disease Following Influenza Vaccination: A Claims-Based Cohort Study Using Propensity Score Matching. Journal of Alzheimer’s disease : JAD, 88(3), 1061–1074.

[4] Addario, A., Célarier, T., Bongue, B., Barth, N., Gavazzi, G., & Botelho-Nevers, E. (2023). Impact of influenza, herpes zoster, and pneumococcal vaccinations on the incidence of cardiovascular events in subjects aged over 65 years: a systematic review. GeroScience, 45(6), 3419–3447.

Date Posted: January 27, 2026

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Rapamycin Protects Immune Cells by Reducing DNA Damage

A new study from the Universities of Oxford and Nottingham has uncovered a potential new mechanism by which rapamycin counters immunosenescence. Rather than increasing autophagy or reducing protein synthesis, the effect appears to involve directly reducing DNA damage burden in immune cells [1].

How can this work?

Rapamycin, a powerful inhibitor of the nutrient-sensing mTOR pathway and probably the small molecule most associated with geroscience, extends lifespan and healthspan in many species [2]. Despite having studied rapamycin for decades, scientists still do not know all the mechanisms behind its geroprotective effect.

It is thought that blocking mTOR shifts energy from growth to maintenance, increasing the process of intracellular junk removal (autophagy) [3]. A new study from the University of Oxford and the University of Nottingham, published in Aging Cell, tests a different hypothesis: that mTOR inhibition directly protects genomic stability in aging immune cells.

Rapamycin decreases DNA lesions

First, the researchers activated T cells from cultured human peripheral blood mononuclear cells (PBMCs) obtained from healthy donors. The cells were then subjected to zeocin, a molecule that induces double-strand breaks in DNA.

Zeocin treatment led to a significant increase in T cells positive for γH2AX, a marker of DNA damage. These cells showed elevated DNA damage response signaling and cellular senescence markers. Cells with high γH2AX levels also exhibited signs of increased mTORC1 but not mTORC2, both of which are protein complexes that mTOR forms.

These surges in γH2AX and mTORC1 activity were greatly attenuated by rapamycin. Moreover, continuous treatment with low-dose rapamycin improved cell survival significantly after DNA damage. T cells treated with rapamycin showed over 60% viability 24 hours post-exposure to zeocin, compared to only 20% in controls.

To see whether treated cells indeed experienced less DNA damage rather than just weaker signaling, the researchers ruled out alternative explanations. The results were not explained by cell-cycle arrest, which could have reduced the readouts. Protein synthesis was also not consistently suppressed.

Autophagy inhibition by chloroquine increased γH2AX positivity, showing that autophagy does help limit damage in these T cells. However, even when autophagy was strongly inhibited, rapamycin still markedly reduced DNA damage markers, suggesting that its protective effect is autophagy-independent.

Finally, the team directly tested DNA damage levels. After zeocin, lesion burden rose, but it was markedly reduced with rapamycin. The authors note that the results may indicate reduced lesion formation, not just faster repair afterward, but this requires further investigation.

Professor Lynne Cox, one of the study’s authors, said, “The cells showed less DNA damage even after only four hours – it’s a very fast response. We don’t yet know whether rapamycin is blocking damage formation or helping cells to repair the damage more quickly and efficiently, so this research opens up a whole new area of study to identify the mechanism of protection.”

“Regardless of whether rapamycin is given before, during, or after DNA damage occurs, we observe a consistent protective response,” added Professor Ghada Alsaleh, a co-author. “These findings uncover a previously unrecognized role of mTOR inhibition in directly protecting the genome, offering new insight into the biological basis of rapamycin’s effects on aging. This suggests that rapamycin, or other mTOR inhibitors, may have broader relevance in contexts involving DNA damage, including healthy aging, clinical radiation exposure, and exposure to cosmic radiation during space travel.”

Confirmed in a small human study

Next, the researchers identified age-associated immune subsets (certain types of T cells, B cells, natural killer cells, and monocytes) in blood samples taken from healthy donors. These aged cells were enriched for markers of DNA damage and senescence, especially p21. There was also more mTORC1 activity broadly across immune cell types in older vs younger donors, suggesting that it is a general biomarker of immune aging, not restricted to one lineage.

Motivated by these findings, the team ran a small randomised placebo-controlled study in older male volunteers. Four people received 1 mg/day of rapamycin, while five received placebo. No significant differences in leukocyte counts were observed after 8 weeks, suggesting that at this dose, rapamycin was not immunosuppressive.

In both groups, mTORC1 activity was positively correlated with γH2AX levels and was lower in the rapamycin group, corresponding with lower γH2AX. The senescence marker p21 dropped robustly across most immune subsets with rapamycin vs placebo after 4 months. The treatment also reduced several T cell exhaustion markers, while p53 expression was elevated at 4 months.

“Our findings provide a new understanding of why rapamycin and other mTOR inhibitors have such promising anti-aging potential in the immune system and more widely across the body,” said Dr. Loren Kell, the lead author. “Since DNA damage is a central driver of immune system aging, our study supports future endeavors to identify more strategies that can improve DNA stability during aging.”

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Literature

[1] Kell, L., Jones, E. J., Gharahdaghi, N., Wilkinson, D. J., Smith, K., Atherton, P. J., … & Alsaleh, G. (2026). Rapamycin exerts its geroprotective effects in the ageing human immune system by enhancing resilience against DNA damage. Aging Cell, 25(2), e70364.

[2] Kaeberlein, M. (2014). Rapamycin and aging: when, for how long, and how much?. Journal of genetics and genomics= Yi chuan xue bao, 41(9), 459.

[3] Kim, Y. C., & Guan, K. L. (2015). mTOR: a pharmacologic target for autophagy regulation. The Journal of clinical investigation, 125(1), 25-32.

Date Posted: January 26, 2026

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Using Placental Cells to Test Anti-Aging Compounds

Researchers publishing in Aging Cell have discovered that cells derived from the human placenta may be useful in estimating the effects of potential anti-aging treatments.

A seemingly odd choice

Of all the organs in the body, the placenta may be the least concerning with regards to aging; it only exists for at most 10 months, after which it is discharged as part of the birthing process. The researchers openly admit that this lifespan difference may make placenta-related aging processes distinct from those in other tissues, which harms translation and generalizability.

However, it is this limited lifespan that makes placental tissue potentially desirable for study. Its lifespan is under half that of mice, and it is made of human cells rather than murine ones. Just like in other organs, senescence and other core aging processes happen in the placenta as well, and unsurprisingly, accelerated placental senescence is linked to preterm birth and other problems [1]. There is also some evidence that the placenta may affect the rest of the body’s aging [2], and placenta-specific genes have been found to be activated in unrelated cells during senescence [3].

These researchers focus on three core placental cell types: cytotrophoblasts (CTBs), which differentiate into multinucleated syncytiotrophoblasts (STBs) and extravillous trophoblasts (EVTs). Differentiating CTBs into STBs can be done within a week in vitro and has been done since 2018 [4]. These researchers focus on this process, determining how similar it is to natural placental aging and how it can be harnessed to study aging more broadly.

Differentiated placental cells age quickly

The researchers first did a thorough examination of STBs compared to CTBs. Tthe differentiated CTBs had significantly more signs of senescence and across-the-board decreases in gene expression related to DNA maintenance, and there were increases in telomere attrition and metabolic differences as well. EVTs were found to have similar differences. Tthe researchers also discovered that results derived from the CTB to STB transition matched well with the epigenetic clock results of stem cells derived from the same donors, leading them to conclude that “cellular aging features observed in other tissue contexts can, therefore, be effectively modeled by the CTB-STB system.”

In their next experiment, the authors used human trophoblast stem cells (hTSCs), which themselves came from human expanded potential stem cells (hEPSCs), in order to ultimately differentiate them into STBs. As expected, these cells were pushed towards senescence as well, exhibiting familiar signs of resistance towards death by apoptosis while becoming more susceptible to death by necroptosis. Other molecular hallmarks of cellular senescence, including p16, were more prevalent as well.

Highly relevant aging features

Very unsurprisingly, this increase in senescence coincided with an increase in the inflammatory senescence-associated secretory phenotype (SASP). Along with telomere maintenance failures, deregulated nutrient sensing, and mitochondrial dysfunction, STBs were far more likely than hTSCs to exhibit SASP upregulation. Interestingly, however, the results between mRNA expression and actual proteins did not match as expected, suggesting a possible age-related change in protein function.

The researchers then tested how well the cells resisted DNA damage. Undifferentiated hTSCs, which contained plenty of active DNA repair pathways as well as protective lamins, were strongly resistant to etoposide, a chemical that damages DNA. STBs, however, had fewer lamin protections and less repair capability; they were far more susceptible, exhibiting signs of double-strand breaks along with the DNA damage marker γH2AX.

This loss of protection also extended to the epigenome. Compared to hTSCs, STBs had significant alterations in histones and histone regulators, which are at the core of epigenetic alterations. H3K9me3 and H3K27me3 were downregulated, H3K4me3 was increased, and total histones and methylation were both decreased; all of these results are in line with those of other aging tissues.

Transposable elements normally found in the human genome, which come loose and become expressed during aging, lead to systemic inflammation [5]. They were far more expressed in STBs than in hTSCs. Knocking down some of these retrotransposons (HERVK) partially suppressed some features of senescence and inflammation in STBs.

Intended for practical use

The researchers then moved on to the possibly most critical portion of their experiment: testing anti-aging molecules against STBs. They began with a screen of the most well-known interventions, including rapamycin, fisetin, NMN, quercetin, resveratrol, and navitoclax. All of these compounds were found to have effects, to varying extents, on the aging of STBs.

While these results are entirely preliminary, this study is meant to, and does, serve as a proof of concept. These are cells that can be rapidly produced and tested to determine the effects of potential anti-aging treatments. While they may not apply to every potential treatment, these cells may be used to accelerate the verification, and thus development, of promising interventions.

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Literature

[1] Kajdy, A., Sys, D., Modzelewski, J., Bogusławska, J., Cymbaluk-Płoska, A., Kwiatkowska, E., … & Kwiatkowski, S. (2023). Evidence of placental aging in late SGA, fetal growth restriction and stillbirth—a systematic review. Biomedicines, 11(7), 1785.

[2] Pham, H., Thompson-Felix, T., Czamara, D., Rasmussen, J. M., Lombroso, A., Entringer, S., … & O’Donnell, K. J. (2024). The effects of pregnancy, its progression, and its cessation on human (maternal) biological aging. Cell metabolism, 36(5), 877-878.

[3] Bi, S., Jiang, X., Ji, Q., Wang, Z., Ren, J., Wang, S., … & Qu, J. (2024). The sirtuin-associated human senescence program converges on the activation of placenta-specific gene PAPPA. Developmental Cell, 59(8), 991-1009.

[4] Okae, H., Toh, H., Sato, T., Hiura, H., Takahashi, S., Shirane, K., … & Arima, T. (2018). Derivation of human trophoblast stem cells. Cell stem cell, 22(1), 50-63.

[5] Liu, X., Liu, Z., Wu, Z., Ren, J., Fan, Y., Sun, L., … & Liu, G. H. (2023). Resurrection of endogenous retroviruses during aging reinforces senescence. Cell, 186(2), 287-304.

Date Posted: January 23, 2026

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Exercise Variety Is Associated With Lower Mortality Risk

A new study links exercise variety, defined as regularly engaging in several types of physical activity, to significantly lower all-cause mortality. Exercise amount matters as well, but the effect plateaus quickly [1].

How exactly is it good for you?

“Exercise is good for you” is a stale truism, but researchers continue to uncover new information about how the amount and specific types of physical activity affect our health. A new study from the Harvard T.H. Chan School of Public Health, published in the journal BMJ Medicine, focuses on the relationship between mortality and the variety of physical activity in two large cohorts of health professionals.

The researchers analyzed data from over 100,000 participants across two major long-term studies (the Nurses’ Health Study and the Health Professionals Follow-Up Study) over a period of 30 years. The former study included only women, while the latter only men. Both cohorts were free at baseline of diabetes, cancer, and any cardiovascular, respiratory, or neurological disease. The levels of physical activity were self-reported every two years. In total, almost 2.5 million person-years were recorded.

Metabolic equivalent of task (MET) is the amount of energy expended during an activity compared to energy expenditure at rest, and in this study, activity doses were expressed as MET-hours/week. For example, brisk walking has a MET value of 3.5 to 4.5, meaning it is about four times more energy-demanding than chilling on a couch.

Lower mortality rates for most types of exercise

Habitual engagement in most measured activities was associated with significantly lower mortality rates. For example, compared to people with the lowest activity levels, the people in the highest categories saw risk reductions of 17% for walking, 15% for tennis and other racquet sports, 14% for rowing/calisthenics, 13% for running and weight/resistance training, and 11% for jogging.

Two activities showed surprisingly low effect sizes: bicycling (4% risk reduction) and swimming (1% risk increase, but statistically insignificant). However, this might simply reflect measurement problems, which is a well-known issue for both cycling and swimming [2].

These mortality benefits from single activities appear more modest than in some earlier studies [3]. One possible reason is that in this study, the comparison group was the lowest quintile of activity, which may not reflect true inactivity, especially since these were groups of of health professionals. The authors also used robust protections against reverse causation (when people lower their activity levels after they become unhealthy), which tends to shrink associations.

Like many recent studies [4], this one shows that mortality risk plateaus at certain levels of activity rather than decreasing indefinitely. However, here, the benefits of exercise peter out rather quickly (at least for cardiovascular, cancer, and respiratory mortality), around 20 MET-hours per week, which may also be due to the reference group not being completely inactive.

Variety matters (usual caveats apply)

The researchers then compared participants with different levels of variety in physical activity, defined as the number of different types of activity that participants regularly performed. After adjusting for total physical activity, the highest-variety group had about a 19% lower all-cause mortality compared to the lowest, with comparable reductions across major causes.

When they combined people into groups by total activity and variety, the highest on both had about 21% lower mortality compared to the lowest-lowest reference group. The authors report no interaction here, signifying that variety helps across activity levels rather than only at high or low volume.

“People naturally choose different activities over time based on their preferences and health conditions. When deciding how to exercise, keep in mind that there may be extra health benefits to engaging in multiple types of physical activity, rather than relying on a single type alone,” said corresponding author Yang Hu, research scientist at the Department of Nutrition.

Anna Whittaker, Professor of Behavioral Medicine at the University of Stirling, who was not involved in this study, said: “This large-scale longitudinal study adds to what we know about the impact of physical activity on mortality by showing that engagement in a range of different types of physical activity is beneficial for longevity, independently of the total amount of physical activity engaged in. This is likely due to the different types of activity having different physiological effects and helping to meet all of the aspects currently outlined in physical activity guidelines (i.e. moderate intensity exercise, resistance exercise, vigorous intensity exercise, flexibility work, recovery activities).”

Like all populational studies, this one can only show correlation, but not causation, and the results depend on many design choices. While the authors did an admirable job controlling for possible confounders, which included age, race/ethnicity, family history of myocardial infarction and cancer, body mass index, smoking, alcohol intake, energy intake, diet quality, social integration, baseline hypertension and hypercholesterolemia, and (for women) postmenopausal hormone use, it is impossible to rule out residual confounding such as sleep, stress, or the built environment. For instance, it is possible that people who can find the time and energy for various types of activity have more free time, enjoy better sleep, and live in an environment better suited for exercise.

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Literature

[1] Han, H., Hu, J., Lee, D. H., Zhang, Y., Giovannucci, E., Stampfer, M. J., Hu, F. B., Hu, Y., & Sun, Q. (2026). Physical activity types, variety, and mortality: Results from two prospective cohort studies. BMJ Medicine, 5(1), e001513.

[2] Harrison, F., Atkin, A. J., van Sluijs, E. M., & Jones, A. P. (2017). Seasonality in swimming and cycling: Exploring a limitation of accelerometer based studies. Preventive medicine reports, 7, 16-19.

[3] Arem, H., Moore, S. C., Patel, A., Hartge, P., De Gonzalez, A. B., Visvanathan, K., … & Matthews, C. E. (2015). Leisure time physical activity and mortality: a detailed pooled analysis of the dose-response relationship. JAMA internal medicine, 175(6), 959-967.

[4] Garcia, L., Pearce, M., Abbas, A., Mok, A., Strain, T., Ali, S., … & Brage, S. (2023). Non-occupational physical activity and risk of cardiovascular disease, cancer and mortality outcomes: a dose–response meta-analysis of large prospective studies. British Journal of Sports Medicine, 57(15), 979-989.

Date Posted: January 22, 2026

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How Senescent Astrocytes Don’t Support Neurons

Resesarchers have found that thrombospondin-1 (TSP-1), a compound that is critical in growing brain synapses, is secreted by normal astrocytes but not senescent ones.

Senescence is harmful to the brain

Cellular Senescence

As your body ages, more of your cells become senescent. Senescent cells do not divide or support the tissues of which they are part; instead, they emit potentially harmful chemical signals, collectively known as the senescence-associated secretory phenotype (SASP), which encourages nearby cells to enter the same senescent state. Their presence causes many problems: they degrade tissue function, increase chronic inflammation, and can even eventually raise the risk of cancer and other age-related ...
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It is well-known that cellular senescence causes brain damage and impairment. The SAMP8 mouse, which is used in this study, has accelerated senescence and quickly develops related brain problems [1]. For example, last year, we reported that senescent microglia are overly aggressive in pruning brain synapses.

This research, however, focuses on astrocytes, other resident brain cells that fulfill a wide variety of maintenance functions [2]. The authors of this paper note that the exact effects of astrocytic senescence on neural synapses have not been particularly well-studied. To remedy this, they closely examined SAMP8 mice to determine how their senescent astrocytes might be indirectly affecting their neurons.

Direct cellular contact is not required

In their first experiments, the researchers verified that hippocampal astrocytes derived the SAMP8 mice were indeed more senescent than those of a control group, including increased expression of the characteristic SA-β-gal. Then, they developed conditioned media (CM) from these astrocytes and discovered that unmodified neural stem cells derived from wild-type mouse embryos were much more able to grow synapses in the CM derived from control astrocytes than in CM from SAMP8 astrocytes. These results held whether the CM was derived from astrocytes differentiated from neural stem cells (NSCs) or from astrocytes directly derived from SAMP8 animals.

The researchers then investigated the molecules present in this CM. As previous work had found that TSP-1 decreases with aging [3] and that its function is critical in cognitive maintenance [4], they took a close look at this particular factor, finding decreases in both the TSP-1 protein and the expression of the Thbs1 gene that encodes it in mice. Once again, these results were verified in both NSC-derived astrocytes and directly taken astrocytes, and unsurprisingly, TSP-1 was also decreased in the hippocampi of SAMP8 mice compared to controls.

Focusing on TSP-1

The biological effects were confirmed through the use of gabapentin, a compound that blocks the receptor of TSP-1. Introducing gabapentin nullified the differences between SAMP8-derived CM and control-derived CM.

Encouraged, the researchers then did the opposite in two ways: they simply added TSP-1 into CM, and they engineered SAMP8 astrocytes to overexpress Thbs1 and then derived CM from those. Both of these approaches had the desired effect: neurons exposed to either one of these CMs were much more able to develop synapses.

It is clear that further work needs to be done to determine whether or not TSP-1 can be used as a functioning strategy in living organisms. The researchers did not attempt to use TSP-1 to treat mice, particularly naturally aged mice, nor did they create a SAMP8 or other model mouse that overexpresses Thbs1. Combined with cognitive tests, such experiments could inform the research world whether or not this might be a viable path to restoring neuroplasticity and cognitive function to older people.

Yes I will donate❤️

Literature

[1] Akiguchi, I., Pallàs, M., Budka, H., Akiyama, H., Ueno, M., Han, J., … & Hosokawa, M. (2017). SAMP8 mice as a neuropathological model of accelerated brain aging and dementia: Toshio Takeda’s legacy and future directions. Neuropathology, 37(4), 293-305.

[2] Phatnani, H., & Maniatis, T. (2015). Astrocytes in neurodegenerative disease. Cold Spring Harbor perspectives in biology, 7(6), a020628.

[3] Clarke, L. E., Liddelow, S. A., Chakraborty, C., Münch, A. E., Heiman, M., & Barres, B. A. (2018). Normal aging induces A1-like astrocyte reactivity. Proceedings of the National Academy of Sciences, 115(8), E1896-E1905.

[4] Cheng, C., Lau, S. K., & Doering, L. C. (2016). Astrocyte-secreted thrombospondin-1 modulates synapse and spine defects in the fragile X mouse model. Molecular brain, 9(1), 74.

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