BUFFALO, NY — April 29, 2025 — A new #research paper was #published in Aging (Aging-US) Volume 17, Issue 3, on March 20, 2025, titled “Inhibition of the metalloprotease ADAM19 as a novel senomorphic strategy to ameliorate gut permeability and senescence markers by modulating senescence-associated secretory phenotype (SASP).”

Researchers, led by first author Sudipta Bar and corresponding authors Amit Sharma and Pankaj Kapahi from the Buck Institute for Research on Aging, have found that the enzyme ADAM19 plays an important role in regulating aging in cells and inflammation in the gut. Their study shows that blocking ADAM19 reduced gut damage and inflammation in fruit flies, mice, and human cells. This discovery points to a new possible way to treat gut disorders related to aging by reducing the harmful signals from senescent (aging) cells.

As individuals age, DNA damage can lead to the accumulation of senescent cells, contributing to tissue damage. These are cells that stop dividing and release harmful inflammatory substances called the senescence-associated secretory phenotype (SASP). In this study, researchers used fruit flies to search for genes involved in radiation-related gut damage. They identified a gene called meltrin, which is similar to human ADAM19. When meltrin was turned off, the flies had less gut leakage, less inflammation, and fewer signs of cellular aging.

“Through an unbiased genome-wide association study (GWAS) utilizing 156 strains from the Drosophila Genetic Reference Panel (DGRP), we identified meltrin (the drosophila orthologue of mammalian ADAM19) as a potential modulator of the senescence-associated secretory phenotype (SASP).”

To test if these results applied beyond flies, the team inhibited ADAM19 in mice using a drug called batimastat. Mice treated with the drug after chemotherapy exposure had stronger gut barriers and lower levels of inflammatory markers. The findings extended to human cell cultures, where ADAM19 inhibition reduced signs of cellular aging, including the expression of SASP proteins and β-galactosidase, a classic aging marker. 

Importantly, this approach does not kill aging cells like many 'senolytic' therapies but instead reduces the harmful substances they release, making it a potential "senomorphic" strategy. The study also showed that ADAM19 helps release certain SASP proteins by cutting them at the cell surface, suggesting a direct role in regulating inflammatory signals.

Through proteomic analysis, the team identified 12 SASP proteins that were significantly reduced when ADAM19 was blocked. Many of these proteins are linked to inflammation, immune response, and tissue remodeling in diseases such as inflammatory bowel disease and Crohn’s disease. This connection underlines the relevance of the findings for treating chronic gut disorders in aging populations.

By targeting ADAM19, researchers may have found a new way to protect gut health and lower inflammation caused by aging cells. This study offers a promising path for creating treatments that maintain healthy tissues without having to destroy aging cells, which could benefit people with gut damage related to aging or medical treatments.

DOI - https://doi.org/10.18632/aging.206224

Corresponding authors - Amit Sharma - amit.sharma@sens.org, and Pankaj Kapahi - pkapahi@buckinstitute.org

Video short - https://www.youtube.com/watch?v=dRfxQ20O2fQ

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Aging (Aging-US)

Inhibiting ADAM19 Reduces Gut Inflammation and Cell Aging Markers Across Species

In this episode, we chat with two winners from our eighth poetry competition. 

Robin, winner of our 'From the heart' category talks about his emotional poem 'Dementia Caring', which is about caring for his late wife Sheila. 

And Kathy, winner of our 'Way with words' category, chats about how her dad Bob inspired her poem 'Is it Time to Go?'.

You can visit alzheimers.org.uk/publications for our range of publications and factsheets designed to support and inform anyone affected by dementia.

For personalised information and advice, call our Dementia support line on 0333 150 3456, or for Welsh speakers call 03300 947 400.

Meet our poetry competition winners – Dementia together podcast October 2025

BUFFALO, NY — October 14, 2025 — A new #research paper was #published in Volume 17, Issue 9 of Aging-US on August 30, 2025, titled, “Glycocalyx-targeted therapy prevents age-related muscle loss and declines in maximal exercise capacity.”

In this study, led by Daniel R. Machin from the University of New Mexico School of Medicine and the University of Utah, researchers found that protecting a fragile layer lining blood vessels, known as the glycocalyx, can prevent muscle deterioration and help maintain physical performance during aging. They also discovered that a supplement containing high-molecular-weight hyaluronan (HMW-HA), a key component of the glycocalyx, enabled older mice to preserve muscle mass and exercise capacity. These findings suggest that targeting the glycocalyx may offer a new approach to reduce frailty and support mobility in older adults.

As this layer degrades with age, it contributes to cardiovascular and muscular decline by impairing blood flow and vascular health. The study examined how preserving the glycocalyx using a therapy called Endocalyx™ affects physical function in aging mice.

Researchers first studied genetically modified mice lacking Has2, the enzyme responsible for producing HMW-HA. These mice had a thinner glycocalyx, reduced exercise performance, and lower mitochondrial function in their muscles, even though muscle size remained normal. This indicated that glycocalyx damage alone can directly impair physical performance.

The team then gave older mice a diet containing Endocalyx™ for 10 weeks. Compared to untreated controls, these mice maintained muscle mass and performed better on treadmill tests. Notably, the treated mice did not show the typical age-related decline in muscle strength and endurance. While the supplement did not fully restore youthful performance, it significantly slowed physical deterioration, suggesting a protective benefit. In contrast, untreated older mice lost both body mass and muscle volume during the same period.

“Taken together, these findings provide direct evidence of a role for HMW-HA in the modulation of exercise capacity.”

This research builds on prior evidence that the glycocalyx is essential for healthy blood vessel function. Since muscle health depends on proper blood flow and oxygen delivery, restoring the glycocalyx may help maintain strength and mobility with age. While more research is needed to confirm these results in humans, the findings point to a potential therapeutic approach to promote healthier aging.

DOI - https://doi.org/10.18632/aging.206313

Corresponding author - Daniel R. Machin — dmachin@salud.unm.edu

Abstract video - https://www.youtube.com/watch?v=S7HjCeXT8fU

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Keywords - aging, glycocalyx, hyaluronan

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Aging-US

Supplement That Supports the Glycocalyx in Blood Vessels May Reduce Frailty in Older Adults

BUFFALO, NY – October 14, 2025 – A new #research paper was #published in Volume 16 of Oncotarget on October 13, 2025, titled “Treatment of glioblastoma with tumor-specific amplitude-modulated radiofrequency electromagnetic fields.”

The study, led by Hugo Jimenez from Wayne State University School of Medicine, Karmanos Cancer Institute, introduces a novel treatment approach for glioblastoma, an aggressive and often treatment-resistant brain cancer. The findings open a new potential path for patients who currently have limited therapeutic options.

The approach uses a device developed by TheraBionic that delivers extremely low levels of radiofrequency electromagnetic fields, tuned to frequencies associated with glioblastoma. In laboratory experiments, this therapy significantly slowed the growth of multiple glioblastoma cell lines. It was especially effective against tumor stem cells, which are known to resist standard treatments and drive cancer reappearance. Researchers also found that the treatment’s effects depend on a calcium channel in tumor cells known as Cav3.2 (CACNA1H). When this channel was blocked, the therapy lost its effectiveness, highlighting the channel’s essential role in how tumor cells respond to the signal. 

The therapy also disrupted the process of cell division by interfering with the mitotic spindle, a structure critical for cell replication. This disruption was associated with changes in the expression of genes that regulate cell division, particularly those involved in the “Mitotic Roles of Polo-Like Kinase” pathway. These effects were specific to tumor-targeted frequencies, as non-matching signals had no measurable impact.

The study also includes data from two patients with difficult-to-treat brain tumors who received the therapy through compassionate use. One patient with recurrent glioblastoma showed signs of clinical and radiographic improvement after one month of treatment. Another patient with oligodendroglioma tolerated the therapy well and had stable disease during follow-up imaging. Neither patient experienced serious side effects, further supporting the safety of the therapy.

“There was evidence of clinical and radiological benefit in a 38-year-old patient with recurrent GB and evidence of safety and feasibility in a 47-year-old patient with oligodendroglioma.”

This is the first study to demonstrate that tumor-specific radiofrequency therapy can suppress both tumor growth and cancer stem cells in glioblastoma. Similar results had previously been observed in liver and breast cancers. These findings contribute to the growing body of evidence supporting a new class of systemic, non-toxic cancer therapies. Further clinical trials will be crucial to confirm these results and fully assess the potential of this approach for treating brain cancer.

DOI - https://doi.org/10.18632/oncotarget.28770

Correspondence to - Hugo Jimenez - hugo.jimenez@wayne.edu

Abstract video - https://www.youtube.com/watch?v=uxYnWcNKYfg

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Keywords - cancer, oncology, amplitude-modulated radiofrequency electromagnetic fields, glioblastoma, TheraBionic, CACNA1H, Cav3.2

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Oncotarget

New Radiofrequency Therapy Slows Glioblastoma Growth and Targets Tumor Stem Cells

As people age, it is common to experience some memory lapses or slower thinking. Although this is often a normal part of aging, it can still affect a person’s quality of life. Scientists have been investigating ways to slow or prevent cognitive decline, and growing evidence points to the potential role of social interaction.

Recently, a study using rats found that long-term social connection may help protect the brain from age-related memory decline. This work, titled “The impact of long-term social housing on biconditional association task performance and neuron ensembles in the anterior cingulate cortex and the hippocampal CA3 region of aged rats,” was recently published in Aging-US (Volume 17, Issue 9).

Full blog - https://aging-us.org/2025/10/how-long-term-social-connection-supports-brain-health-and-memory-in-aging/

Paper DOI - https://doi.org/10.18632/aging.206310

Corresponding author - Anne M. Dankert - adankert@unc.edu

Abstract video - https://www.youtube.com/watch?v=poNnPz1ti6Q

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Keywords - aging, aging, environmental enrichment, working memory, complex cognition, immediate early genes

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How Long-Term Social Connection Supports Brain Health and Memory in Aging

BUFFALO, NY — October 17, 2025 — A new #research paper was #published in Volume 17, Issue 9 of Aging-US on September 8, 2025, titled, “Runx1 overexpression induces early onset of intervertebral disc degeneration.”

In this study, led by first author Takanori Fukunaga from Emory University School of Medicine and corresponding author Hicham Drissi from Emory and the Atlanta VA Medical Center, researchers found that the Runx1 gene, when overactive in spinal disc cells, can accelerate age-related degeneration of the intervertebral discs. The findings offer new insight into the genetic factors that drive disc aging and suggest possible directions for treating chronic back pain.

Intervertebral discs cushion the spine and support movement. Their deterioration is a major cause of lower back pain, especially with aging. At the center of each disc is the nucleus pulposus (NP), a gel-like core that contains proteins such as collagen and aggrecan, which help retain water and maintain structure. As people age, NP cells often lose their function, contributing to disc breakdown.

Using a genetically modified mouse model, the researchers activated Runx1 specifically in NP cells. These mice developed signs of disc degeneration by five months of age, which is much earlier than normal. The overexpression of Runx1 led to the loss of healthy NP cells, an increase in abnormal cell types, and damage to disc structure. Levels of essential proteins like aggrecan and type II collagen decreased, while type X collagen increased, signaling unhealthy tissue changes.

“To achieve NP-specific postnatal overexpression of Runx1, we crossed Krt19CreERT mice with Rosa26-Runx1 transgenic mice previously generated in our laboratory.”

A key finding was that Runx1 overactivity did not kill cells directly. Instead, it caused premature cellular aging, known as senescence. Senescent cells lose the ability to repair tissue, creating an environment that accelerates degeneration. Markers of senescence were significantly elevated in the affected discs.

The researchers also observed a dose-dependent response. The more Runx1 was activated, the more severe the degeneration was. This suggests that targeting Runx1 may be a promising strategy to prevent or slow disc aging.

Overall, this study highlights the genetic and cellular processes that contribute to intervertebral disc degeneration, a leading cause of disability. By identifying Runx1 as a potential driver of early disc aging, the research opens new opportunities for intervention and treatment of degenerative spine conditions.

DOI - https://doi.org/10.18632/aging.206316

Corresponding author - Hicham Drissi - hicham.drissi@emory.edu

Abstract video - https://www.youtube.com/watch?v=BPwWbVBPIUM

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Keywords - cell senescence, aging, Runx1, nucleus pulposus, intervertebral disc degeneration

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Overactive Runx1 Gene Triggers Early Disc Degeneration Linked to Aging

BUFFALO, NY – October 20, 2025 – A new #research paper was #published in Volume 16 of Oncotarget on October 16, 2025, titled “Widespread folate receptor expression in pediatric and adolescent solid tumors – opportunity for intraoperative visualization with the novel fluorescent agent pafolacianine.”

In this study, led by first author Ashley C. Dodd from Ann & Robert H. Lurie Children’s Hospital and corresponding author Timothy B. Lautz from the same institution and Northwestern University Feinberg School of Medicine, researchers discovered that folate receptor beta (FRβ) is widely expressed in various pediatric and adolescent solid tumors. This finding highlights FRβ as a promising target for improving the accuracy of tumor surgery using a fluorescent imaging agent known as pafolacianine.

Pediatric cancers are often challenging to remove completely during surgery, particularly when tumors spread or form small metastases. Fluorescence-guided surgery is a method that helps surgeons better identify tumors during operations using special imaging dyes. However, commonly used dyes such as indocyanine green are not tumor-specific and rely on general features of blood vessel permeability, limiting their precision.

In this study, researchers investigated the potential of pafolacianine, a next-generation dye that targets folate receptors, for pediatric use. Folate receptors are proteins commonly found on the surface of cancer cells. Pafolacianine is already FDA-approved for adults with ovarian and lung cancers due to its ability to bind these receptors and highlight tumors during surgery. 

The research team analyzed tissue samples from 13 young patients diagnosed with various cancers, including Wilms tumor, osteosarcoma, synovial sarcoma, rhabdomyosarcoma, Ewing sarcoma, and neuroblastoma. The results showed that FRα was predominantly absent, whereas FRβ was present in 100% of the tumor samples. Notably, FRβ appeared both on the tumor cells and in the surrounding tumor microenvironment but showed little to no expression in normal tissue, making it an excellent candidate for targeted imaging.

“In this study, we performed immunohistochemistry staining on slides obtained from a range of pediatric patients with solid tumors.”

This consistent expression of FRβ in pediatric tumors is a significant and novel finding. Earlier studies primarily linked FRβ to immune cells called tumor-associated macrophages. This study reveals that FRβ is also expressed directly on tumor tissue, which could help surgeons better distinguish cancer from healthy tissue during procedures.

Based on these results, the team has launched a clinical trial to evaluate pafolacianine in children undergoing surgery for metastatic lung tumors. If successful, this method could make pediatric cancer surgery safer and more effective.

Overall, this study suggests that targeting FRβ with pafolacianine could serve as a tumor-agnostic imaging strategy, applicable across a wide range of pediatric solid tumors. This represents a potential advancement in real-time surgical imaging and a step forward in pediatric cancer care.

DOI - https://doi.org/10.18632/oncotarget.28772

Correspondence to - Timothy B. Lautz - TLautz@luriechildrens.org

Abstract video - https://www.youtube.com/watch?v=0its0QkOcwM

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Folate Receptor Beta Found in Pediatric Tumors May Improve Fluorescence-Guided Cancer Surgery

BUFFALO, NY — October 21, 2025 — A new #editorial was #published in Aging-US on October 13, 2025, titled “Longevity clinics: between promise and peril.”

In this editorial, Marco Demaria, Editor-in-Chief of Aging-US, from the European Research Institute for the Biology of Ageing (ERIBA), University Medical Center Groningen (UMCG), University of Groningen (RUG), reviews the rapid rise of longevity clinics worldwide. 

Longevity clinics have emerged globally in response to increasing demand for personalized, preventive healthcare. Located in countries such as the United States, Switzerland, and the United Arab Emirates, these centers offer advanced diagnostic services, including genomic testing, advanced imaging, and multi-omics profiling. Their goal is to extend healthspan—the number of years a person lives in good health—through customized lifestyle interventions, nutritional guidance, and, in some cases, experimental therapies.

“Longevity clinics embody an important vision: healthcare is personalized, preventive, and engaged.”

Although the concept of proactive aging care is attractive, the editorial raises serious concerns about the scientific and ethical foundations of these clinics. Many operate outside conventional medical systems and lack connections to academic geroscience. This disconnection allows them to market expensive interventions without sufficient clinical validation. Program costs can range from €10,000 to over €100,000 per year, limiting access to wealthy individuals while leaving out populations most at risk for premature aging.

Despite these challenges, Dr. Demaria notes that longevity clinics may contribute meaningfully to innovation. By collecting extensive, long-term health data from clients, these clinics have the potential to identify early biomarkers of aging and detect signs of age-related diseases. Unlike traditional clinical trials, which are limited in scope and duration, longevity clinics track a wide range of health data over time. When paired with artificial intelligence tools, this information could help advance the science of healthy aging.

However, several risks remain. Many clinics lack standardized protocols, and the tools they use, such as biological age calculators or hormone therapies, often lack accuracy or clear clinical value. Without proper guidelines, clients may receive advice that is confusing or not scientifically supported. This can reduce public trust in the broader field of longevity research.

To ensure these clinics contribute positively to health innovation, the editorial outlines different key steps: greater collaboration with academic researchers, the adoption of standardized protocols, increased transparency, and work toward regulatory clarity. Broader access must also be considered by developing scalable and more affordable models, possibly through partnerships with public health systems.

Ultimately, longevity clinics represent both a major opportunity and a serious concern. If integrated responsibly with science, policy, and public health, they could support a shift toward personalized, preventive healthcare. Without this alignment, however, they risk reinforcing inequality and weakening the credibility of the science behind aging.

DOI - https://doi.org/10.18632/aging.206330

Corresponding author - Marco Demaria — m.demaria@umcg.nl

Abstract video - https://www.youtube.com/watch?v=Bt84xBdii0s

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The Rise of Longevity Clinics: Promise, Risk, and the Future of Aging

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare blood cancer that primarily affects older adults. One of the key challenges in diagnosing and treating BPDCN is that it closely resembles other forms of leukemia in both appearance and behavior. This overlap often leads to delays or uncertainty in diagnosis, especially since currently there is no single, reliable marker that clearly distinguishes BPDCN from related diseases.

To address this issue, researchers from the City of Hope Comprehensive Cancer Center investigated the genetic profile of BPDCN.  Their study, titled “Genetic characteristics of blastic plasmacytoid dendritic cell neoplasm: A single institution experience,” was published in Oncotarget (Volume 16).

Full blog - https://www.oncotarget.org/2025/10/22/genetic-study-identifies-potential-diagnostic-marker-for-rare-blood-cancer-bpdcn/

Paper DOI - https://doi.org/10.18632/oncotarget.28742

Correspondence to - Michelle Afkhami - mafkhami@coh.org

Abstract video - https://www.youtube.com/watch?v=wUjr3uU3onI

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Keywords - cancer, Blastic plasmacytoid dendritic cell neoplasm (BPDCN), Next-generation sequencing (NGS), CCDC50

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Genetic Study Identifies Potential Diagnostic Marker for Rare Blood Cancer BPDCN

BUFFALO, NY — October 23, 2025 — A new #research paper was #published in Volume 17, Issue 9 of Aging-US on September 11, 2025, titled “Roles of plasminogen activator inhibitor-1 in aging-related muscle and bone loss in mice.”

In this study led by first author Takashi Ohira and corresponding author Hiroshi Kaji from Kindai University Faculty of Medicine, researchers found that female mice lacking the gene for plasminogen activator inhibitor-1 (PAI-1) were protected from age-related muscle weakness and bone thinning. This suggests that PAI-1 could be a potential target for future treatments to reduce frailty in aging populations.

As the global population continues to age, more people are affected by conditions such as sarcopenia and osteoporosis. These disorders involve the progressive loss of skeletal muscle mass and bone density, leading to reduced mobility, a greater risk of falls, and a lower quality of life.

To investigate the role of PAI-1 in aging, researchers compared young (6-month-old) and aged (24-month-old) male and female mice, with and without the PAI-1 gene. They found that PAI-1 levels increased with age in both sexes. However, only female mice lacking the PAI-1 gene experienced a significant reduction in age-related muscle and bone loss.

Female mice without PAI-1 maintained stronger grip strength and greater muscle mass in their lower limbs. They also showed less cortical bone loss in their femurs and tibias. In contrast, male mice did not experience the same benefits, despite also showing increased levels of PAI-1 with age. These results suggest that PAI-1 contributes to aging-related decline in a sex-specific manner.

“The present study found that lower limb muscle mass, gastrocnemius and soleus muscle tissue weights, and grip strength were significantly lower in 24-month-old male and female wild-type mice than in their 6-month-old counterparts.”

PAI-1 plays key roles in blood clotting, inflammation, and cellular senescence—a process in which aging cells release harmful molecules that affect nearby tissues. One of these molecules, interleukin-6 (IL-6), is a major driver of inflammation. The researchers found that aged female mice lacking PAI-1 had lower IL-6 levels in both muscle and blood, suggesting that PAI-1 may contribute to muscle and bone loss by promoting inflammation. These protective effects were also not associated with changes in muscle protein turnover or reductions in fibrous tissue, reinforcing the idea that PAI-1’s impact is likely driven by inflammatory signaling.

This study highlights PAI-1 as a promising therapeutic target for slowing or preventing age-related declines in muscle and bone health, particularly in women. Since postmenopausal women are especially vulnerable to osteoporosis and frailty, a better understanding of how PAI-1 contributes to aging could lead to new strategies for maintaining strength and mobility in later life. Further research is needed to explore how PAI-1 interacts with other age-related biological changes and why its effects differ between sexes.

DOI - https://doi.org/10.18632/aging.206318

Corresponding author - Hiroshi Kaji - hkaji@med.kindai.ac.jp

Abstract video - https://www.youtube.com/watch?v=hg4qKf-oO2I

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PAI-1 Deficiency Protects Aging Female Mice from Muscle and Bone Loss

BUFFALO, NY — October 27, 2025 — A new #research paper was #published in Volume 17, Issue 9 of Aging-US on September 17, 2025, titled “Depletion of the TRF1 telomere-binding protein leads to leaner mice with altered metabolic profiles.”

In this study led by first author Jessica Louzame Ruano and corresponding author Maria A. Blasco from the Spanish National Cancer Centre (CNIO), researchers investigated the role of TRF1, a protein known for protecting telomeres, in regulating whole-body metabolism. The results suggest that TRF1 influences metabolic health through mechanisms unrelated to its known function in telomere maintenance.

Obesity and metabolic disorders are major health concerns, especially as people age. To explore TRF1’s role beyond telomere protection, the research team studied both normal mice and genetically modified mice that lacked TRF1. Mice without TRF1 remained leaner over time, resisted fat accumulation, and showed healthier blood sugar and insulin levels compared to normal mice. Importantly, these benefits occurred without any detectable shortening of telomeres.

The leaner body composition in TRF1-deficient mice was not due to reduced food intake or increased physical activity. Instead, the fat loss appeared to result from biological changes in how energy was processed and stored. Male mice without TRF1 gained less weight and had lower LDL cholesterol levels, even on a high-fat diet. Female mice showed milder effects, reflecting known sex-based differences in susceptibility to diet-induced obesity. This highlights the importance of including both sexes in metabolic research.

“Major metabolic pathways related with energy production and regulation of metabolism homeostasis were also found downregulated in Trf1-deficient mice.”

Gene expression analysis in the liver revealed shifts in several key pathways. Genes related to fat production, energy generation, and muscle growth were downregulated, while genes linked to inflammation and cholesterol synthesis were upregulated. The mice also showed signs of higher energy expenditure and a shift from using fat to protein as an energy source, possibly due to their reduced fat reserves. However, some older mice developed mild liver stress, including fibrosis and DNA damage, suggesting a possible long-term trade-off.

Overall, this study expands the understanding of how telomere-related proteins influence more than just cellular aging. By identifying a connection between TRF1 and metabolism, the research opens new possibilities for targeting TRF1 or its pathways to address obesity and related conditions. Still, further studies are needed to clarify how TRF1 affects fat development and whether similar effects occur in humans.

DOI - https://doi.org/10.18632/aging.206320

Corresponding author - Maria A. Blasco — mblasco@cnio.es

Abstract video - https://www.youtube.com/watch?v=7AG3TBgDZIw

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Keywords - aging, Trf1, metabolism, leaner, fat, telomeres

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TRF1 Protein Loss Reduces Body Fat and Improves Metabolic Health in Mice Without Shortening Telomeres

TRF1 Protein Loss Reduces Fat and Improves Metabolic Health in Mice Without Shortening Telomeres

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