Federica Grosso from the  Institute for Genetic and Biomedical Research (IRGB) of the National Research Council (CNR) in Monserrato, Italy, describes a #research paper she co-authored that was #published in Volume 17, Issue 8 of Aging-US, entitled “Causal relationships between gut microbiome and hundreds of age-related traits: evidence of a replicable effect on ApoM protein levels.”

DOI - https://doi.org/10.18632/aging.206293

Corresponding author - Serena Sanna - serena.sanna@cnr.it

Video interview - https://www.youtube.com/watch?v=qYg42_gn_pw

Abstract

In the past 20 years, the involvement of gut microbiome in human health has received particular attention, but its contribution to age-related diseases remains unclear. To address this, we performed a comprehensive two-sample Mendelian Randomization investigation, testing 55130 potential causal relationships between 37 traits representing gut microbiome composition and function and age-related phenotypes, including 1472 inflammatory and cardiometabolic circulating plasma proteins from UK Biobank Pharma Proteomic Project and 18 complex traits. A total of 91 causal relationships remained significant after multiple testing correction (false discovery rate p-value <0.05) and sensitivity analyses, notably two with the risk of developing age-related macular degeneration and 89 with plasma proteins. The link between purine nucleotides degradation II aerobic pathway and apolipoprotein M was further replicated using independent genome-wide association study data. Finally, by taking advantage of previously reported biological function of Faecalibacterium prausnitzii we found evidence of regulation of six proteins by its function as mucosal-A antigen utilization. These results support the role of gut microbiome as modulator of the inflammatory and cardiometabolic circuits, that may contribute to the onset of age-related diseases, albeit future studies are needed to investigate the underlying biological mechanisms.

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Keywords - aging, causal inference, aging, gut microbiome, inflammatory proteins, age-related macular degeneration

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Behind the Study: Gut Microbiome Links to Age-Related Traits and ApoM Protein

BUFFALO, NY – October 8, 2025 – A new #research paper was #published in Volume 16 of Oncotarget on October 6, 2025, titled “ACTM-838, a novel systemically delivered bacterial immunotherapy that enriches in solid tumors and delivers IL-15/IL-15Rα and STING payloads to engage innate and adaptive immunity in the TME and enable a durable anti-tumor immune response.”

In this study, led by first author Kyle R. Cron and corresponding author Akshata R. Udyavar, researchers from Actym Therapeutics developed a new form of bacterial immunotherapy called ACTM-838. This treatment safely delivers immune-activating proteins directly to solid tumors. The approach may offer a new option for cancer patients whose solid tumors are resistant to current immunotherapies.

Solid tumors often suppress the immune system, making it difficult for treatments like immune checkpoint inhibitors to work effectively. ACTM-838 was designed to overcome this challenge by targeting phagocytic immune cells within the tumor microenvironment (TME). Once inside the tumor, the therapy delivers two immune-stimulating components: IL-15/IL-15Rα and a modified version of STING. Both are known to activate the body’s innate and adaptive immune responses. This combination of immune-stimulating proteins helps shift the TME from immune-suppressive to immune-permissive, enabling the body’s natural defenses to fight the cancer.

“STACT is a modular, genetically engineered live attenuated S. Typhimurium bacterial platform that enables tissue-specific localization and cell-targeted delivery of large, multiplexed payloads via systemic administration.”

The study highlights how ACTM-838, built on a specially modified strain of Salmonella Typhimurium, safely targets tumors and avoids healthy tissue after intravenous injection. This targeted delivery reduces the risk of side effects while ensuring the immune-boosting agents reach their intended location. Importantly, ACTM-838 also showed significantly reduced inflammatory toxicity compared to its parent bacterial strain, which had previously presented challenges in clinical use.

In preclinical tests, ACTM-838 shrank tumors and prevented their recurrence after treatment. Mice that were cured of tumors resisted re-injection with cancer cells, suggesting the development of long-lasting immune memory. The therapy also showed strong synergy with anti-PD1 drugs, a widely used class of cancer treatments, further improving outcomes in both treatment-resistant and responsive tumor models.

Researchers also found that ACTM-838 changed the composition of immune cells within the tumor. It increased beneficial cells like cytotoxic T-cells and antigen-presenting macrophages, while reducing suppressive cell types such as regulatory T-cells and exhausted T-cells. These effects were confirmed through genetic analysis and cellular studies, pointing to a broad and coordinated immune response.

This study offers proof-of-concept that live bacterial therapy can safely and effectively deliver gene-based immune modulators directly to tumors. With ACTM-838 now being tested in a Phase I clinical trial, the findings offer a new direction for cancer treatment strategies that activate the body’s own immune system, particularly in difficult-to-treat cases where other therapies fail.

DOI - https://doi.org/10.18632/oncotarget.28769

Correspondence to - Akshata R. Udyavar - akshata.udyavar@pfizer.com

Abstract video - https://www.youtube.com/watch?v=fr5OR3tvC_I

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Oncotarget

Engineered Bacterial Therapy Activates Immune Response in Cancer Preclinical Studies

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

Dr. Leonard Egede, Dr. Rebekah Walker, and Dr. Obinna Ekwunife from the Department of Medicine at the University of Buffalo, NY, describe their #research paper #published in Volume 17, Issue 8 of Aging-US, entitled “Longitudinal relationship between social and CVD risk factors in older adults with prediabetes: the HRS 2006-2016.”
#interview #authorinterview #aging #prediabetes #cardiovascular #health #openaccess #openscience #peerreviewed #journal #publication #publishing #meded

DOI - https://doi.org/10.18632/aging.206308

Corresponding author - Leonard E. Egede - legede@buffalo.edu

Video interview - https://www.youtube.com/watch?v=1MSTk3GQAGA

Video transcript - https://aging-us.net/2025/10/08/behind-the-study-social-and-cardiovascular-risk-factors-in-older-adults-with-prediabetes/

Abstract

Background: This study examines how multiple social risk factors influence cardiovascular disease (CVD) risk control over time in older adults with prediabetes using a nationally representative cohort.

Methods: Data from the Health and Retirement Study (HRS) included 5,086 U.S. adults aged 50+ with prediabetes. Five social risk domains (economic stability, environment, education, healthcare, and social context) were examined as independent variables, while CVD risk factors included glycemic control (HbA1c), systolic blood pressure (SBP), and cholesterol ratio (total cholesterol/high-density lipoprotein). Mixed-effects models assessed relationships between social risk factors and CVD outcomes, adjusting for age, gender, race, and marital status.

Results: The sample had an average age of 68.6 years, with 60.2% female, and 70.97% identifying as non-Hispanic Black. Average HbA1c was 5.7, SBP 129.4, and cholesterol ratio 3.85. Limited education was consistently associated with increased CVD risk—HbA1c (β = 0.03, 95% CI: 0.01–0.06, p < 0.001), SBP (β = 4.34, 95% CI: 2.96–5.71, p < 0.001), and cholesterol ratio (β = 0.08, 95% CI: 0.01–0.16, p < 0.05) —in the fully adjusted model. Medication cost-related non-adherence was significantly associated with higher HbA1c levels (β = 0.03, 95% CI: 0.002–0.06, p < 0.05). Difficulty paying bills and lack of health insurance were both significantly associated with higher cholesterol levels (β = 0.03, 95% CI: 0.002–0.06, p < 0.05) and (β = 0.22, 95% CI: 0.15–0.30, p < 0.001), respectively.

Conclusions: Social risk factors, particularly limited education, significantly impact CVD risk in older adults with prediabetes.

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Keywords - aging, prediabetes, social determinants of health, health equity, cardiovascular health, population health

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Behind the Study: Social and Cardiovascular Risk Factors in Older Adults with Prediabetes

Lung cancer remains one of the leading causes of cancer-related deaths worldwide. Although precision medicine has improved outcomes for many patients, certain rare genetic mutations are still poorly understood, particularly in regions with limited access to genomic testing. Such mutations involve the HER2 gene, better known for its role in breast cancer but also implicated in a small subset of lung cancers.

HER2 mutations are found in approximately 2–4% of non-small cell lung cancer (NSCLC) cases and create unique challenges. These tumors can vary significantly in how they appear under a microscope and in how they respond to treatment. Adding to the complexity, most diagnostic and treatment guidelines are based on research from high-income countries, which may not reflect the genetic diversity seen in other parts of the world.

To help close this knowledge gap, researchers in Northeastern Brazil conducted one of the first detailed investigations into HER2-mutated NSCLC in Latin America. Their study, recently published in Volume 16 of Oncotarget, reveals a complex and often overlooked form of the disease, highlighting the need for broader access to targeted therapies in underserved populations.

Full blog - https://www.oncotarget.org/2025/10/08/new-insights-into-her2-mutated-non-small-cell-lung-cancer-in-brazil/

Paper DOI - https://doi.org/10.18632/oncotarget.28737

Correspondence to - Fabio Tavora - stellacpak@outlook.com

Abstract video - https://www.youtube.com/watch?v=hr5R9iDBFFI

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Keywords - cancer, HER2 mutation, NSCLC, lung cancer, targeted therapy, genomic profiling

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New Insights into HER2-Mutated Non-Small Cell Lung Cancer in Brazil

BUFFALO, NY — October 9, 2025 — A new #research paper was #published in Volume 17, Issue 9 of Aging-US on August 22, 2025, 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.”

The research team led by Anne M. Dankert from Providence College and University of North Carolina, Chapel Hill, showed that aged rats who lived in socially enriched environments throughout life retained better memory and cognitive flexibility than those housed alone. This study highlights the importance of social interaction in protecting the aging brain.

Cognitive decline, such as memory loss and reduced problem-solving ability, affects many people over the age of 65. While many factors contribute to age-related cognitive decline, this study suggests that one key factor may be surprisingly simple: long-term social connection. To explore how social interaction might influence memory performance and brain activity, the researchers designed a study using rats as a model for aging in humans.

“Cognitive decline and changes in neuronal activity are hallmarks of aging.”

They compared three groups of rats: young adults, aged rats housed alone, and aged rats housed socially in groups. All groups had access to the same physical enrichment, such as exercise and stimulating objects, but only some experienced lifelong social companionship. The team tested these animals on a complex memory challenge known as the biconditional association task, which requires animals to make context-based decisions—an ability that typically declines with age.

The results showed that aged rats living in social groups performed just as well as young adults on the memory task, while those housed alone showed significant impairments. Socially housed rats also made fewer working memory errors and required less effort to complete cognitive tasks, suggesting not only better performance but more efficient brain function. These benefits were not observed in aged rats who received only environmental enrichment without social interaction.

Brain imaging revealed additional differences between the groups. Socially housed aged rats showed increased activity in the hippocampus, particularly in the CA3 region, which plays a key role in forming and separating memories. In contrast, aged rats that lived alone had lower activity in this region, which may explain their poorer performance. Interestingly, socially housed rats also showed reduced overactivity in the anterior cingulate cortex—a brain area involved in attention and decision-making—suggesting a more balanced and efficient neural response.

This research provides new insight into how lifelong social experiences shape brain health during aging. While earlier studies have shown that physical activity and cognitive stimulation help preserve cognitive function, this study identifies social interaction as an independent and powerful protective factor. The findings are consistent with human studies showing that older adults who remain socially active tend to experience slower cognitive decline and stronger brain function.

Overall, these results emphasize that brain aging is not inevitable but may be influenced by our social environments. This research suggests that fostering lifelong social connections could be a critical, low-cost strategy to protect memory and mental flexibility in older adults.

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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Lifelong Companionship Protects Aging Rat Brains from Cognitive Decline

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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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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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

Aging-US is dedicated to advancing our understanding of the biological mechanisms that drive aging and the development of age-related diseases. Our mission is to serve as a platform for high-quality research that uncovers the cellular, molecular, and systemic processes underlying aging, and translates these insights into strategies to extend healthspan and delay the onset of chronic disease.

Read about the Aging (Aging-US) Scientific Integrity Process: https://aging-us.com/scientific-integrity

Overactive Runx1 Gene Triggers Early Disc Degeneration Linked to Aging

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