BUFFALO, NY — July 15, 2025 — A new #research paper was #published in Aging (Aging-US) Volume 17, Issue 6, on June 5, 2025, titled “Senescence caused by telomerase inactivation in myeloid, mesenchymal, and endothelial cells has distinct effects on cancer progression.”

In this study, first author Joseph Rupert, along with corresponding author Mikhail G. Kolonin and colleagues from The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, McGovern Medical School, at The University of Texas Health Sciences Center at Houston, investigated how aging-related changes in different cell types affect cancer progression. By turning off telomerase in specific cell populations in mice, the researchers discovered that cell aging, or senescence, can slow primary tumor growth but also trigger unexpected effects. This work sheds light on the complex relationship between aging cells and cancer and may help guide future anti-cancer strategies.

The team used genetically modified mice to deactivate telomerase, the enzyme that maintains chromosome ends, specifically in immune, connective tissue, and blood vessel cells. This caused these cells to enter a state of senescence, where they stop dividing and release inflammatory signals. The researchers then implanted breast, prostate, and pancreatic cancer cells into the mice and tracked how tumors developed. They found that when telomerase was inactivated in immune cells or connective tissue cells, tumors grew more slowly. However, these tumors showed signs of increased tissue damage and potential aggressiveness.

Interestingly, when telomerase was turned off in endothelial cells, which cover blood vessels, tumors shrank and became poorly supplied with blood, leading to oxygen deprivation. In the case of pancreatic cancer cells, this low-oxygen environment made them more likely to spread to the liver, highlighting a potential risk of targeting these cells.

“[…] this study shows that senescence and metabolic dysfunction resulting from telomerase inactivation in distinct cells in the tumor microenvironment have different effects on tumor growth and metastasizing of carcinomas.”

This research provides important insights into how aging cells within the tumor microenvironment (TME) influence cancer behavior. While senescence in certain cell types can help suppress tumor growth, it may also create conditions that favor cancer metastasis. These findings highlight the need to consider cell type-specific effects when developing therapies that target senescent cells. By mapping how different cell populations contribute to cancer progression in aging tissues, this study opens the door for more precise approaches to prevent both tumor growth and spread.

DOI - https://doi.org/10.18632/aging.206268

Corresponding author - Mikhail G. Kolonin - mikhail.g.kolonin@uth.tmc.edu

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Keywords - aging, senescence, telomerase, myeloid, mesenchymal, endothelial

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Aging (Aging-US)

How Telomerase Inactivation in Aging Cells Influences Cancer Growth and Metastasis

*Content warning: this episode features references to suicidal thoughts.

In this episode, we chat with Steve in Fermanagh about living with young-onset Alzheimer’s disease.

After his diagnosis, Steve had to retire from his beloved job as a long-distance truck driver. But he's found new sources of joy, and the strength and confidence to advocate for other people living with dementia.  

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.

‘I've found a different me’ – Dementia together podcast August 2025

BUFFALO, NY — August 19, 2025 — A new #research paper was #published in Volume 17, Issue 7 of Aging (Aging-US) on July 7, 2025, titled “Epigenetic age and accelerated aging phenotypes: a tumor biomarker for predicting colorectal cancer.”

In this study led by Su Yon Jung from the University of California, Los Angeles, researchers found a strong association between accelerated epigenetic aging and an increased risk of colorectal cancer in postmenopausal women. The study also indicated that lifestyle factors influence this risk.

Colorectal cancer is one of the leading causes of cancer-related deaths worldwide, particularly in people over the age of 50. However, individuals do not all age at the same biological rate. Two people of the same chronological age can differ in their biological aging, which reflects the condition of their cells and tissues. This study focused on a specific measure of biological aging known as epigenetic aging, which is based on chemical changes to DNA.

The researchers used data from the Women’s Health Initiative Database for Genotypes and Phenotypes (WHI-dbGaP), which includes genetic and health information from postmenopausal white women aged 50 to 79. They applied three established “epigenetic clocks” to estimate epigenetic age from blood samples collected up to 17 years before a colorectal cancer diagnosis. These clocks measure how quickly a person is aging at the molecular level by tracking DNA methylation. Women with a higher epigenetic age than expected were significantly more likely to develop colorectal cancer

“[…]we examined biological aging status in PBLs via three well-established epigenetic clocks—Horvath’s, Hannum’s and Levine’s […].”

The study also explored the role of lifestyle in modifying this risk. Women who consumed more fruits and vegetables showed no increased risk, even if they were epigenetically older. In contrast, women with both lower fruit and vegetable intake and signs of accelerated aging were up to 20 times more likely to develop colorectal cancer. This suggests that a healthy diet may help reduce cancer risk associated with biological aging.

Another key finding involved women who had both ovaries removed before natural menopause. These women had a higher epigenetic age and, when combined with accelerated aging, a greater likelihood of developing colorectal cancer. This highlights the potential influence of hormonal and reproductive factors on aging and disease risk.

The researchers validated their findings across several independent datasets, supporting the potential of blood-based epigenetic aging markers as early indicators of colorectal cancer risk. These markers could help guide early detection and prevention strategies in aging populations. However, the authors emphasize the need for independent large-scale replication studies.

Overall, this study contributes to a better understanding of the association between epigenetic aging and cancer. It also supports the idea that modifiable lifestyle factors may reduce disease risk, even among those aging more rapidly at the cellular level.

DOI - https://doi.org/10.18632/aging.206276

Corresponding author - Su Yon Jung - sjung@sonnet.ucla.edu

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Epigenetic Aging Markers Predict Colorectal Cancer Risk in Postmenopausal Women

A new #study published as the #cover of Aging (Aging-US) Volume 17, Issue 7, explores how factors in young human blood may affect the biological age of human skin. Researchers from Beiersdorf AG, Research and Development Hamburg in Germany, used a microphysiological co-culture system—a lab-based model simulating human circulation—to test the effects of young versus old blood serum on skin cells. The findings suggest that bone marrow-derived cells play a key role in converting blood-borne signals into effects that support skin rejuvenation.

Understanding Skin Aging and Systemic Influence

As we age, the skin’s ability to regenerate declines, while its biological age increases. This contributes to visible signs of aging and a weakened barrier function. While cosmetic treatments can improve appearance, they rarely target the cellular processes underlying skin aging.

Animal studies have shown that exposure to young blood can promote tissue repair and rejuvenation, likely due to molecules circulating in the bloodstream. However, reproducing these effects in human skin has proven difficult. Applying young serum directly to skin tissue has not produced significant results, indicating that additional cellular interactions may be required.

Full blog - https://aging-us.org/2025/08/skin-rejuvenation-how-young-blood-and-bone-marrow-influence-it/

Paper DOI - https://doi.org/10.18632/aging.206288

Corresponding author - Elke Grönniger - elke.groenniger@beiersdorf.com

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Keywords - aging, skin rejuvenation, microphysiological systems, systemic factors, bone marrow model, human serum

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Skin Rejuvenation: How Young Blood and Bone Marrow Influence It

BUFFALO, NY – August 19, 2025 – A new #research paper was #published in Volume 16 of Oncotarget on August 19, 2025, titled “The SCD1 inhibitor aramchol interacts with regorafenib to kill GI tumor cells in vitro and in vivo.”

In this study, led by first authors Laurence Booth and Michael R. Booth, along with corresponding author Paul Dent from Virginia Commonwealth University, researchers investigated how aramchol, a drug originally developed for liver disease, works with the cancer drug regorafenib in gastrointestinal (GI) tumor cells. They found that the combination is effective, especially in tumor cells with a specific genetic variant. The combined approach offers a potential new strategy for treating liver and colon cancers.

Gastrointestinal cancers, such as liver and colon cancer, are serious global health challenges. Regorafenib, already approved for cancer treatment, can have limited impact and frequently causes side effects. Aramchol, a drug developed to treat fatty liver disease, affects how cancer cells process fats and energy. In this study, researchers tested whether combining these two drugs could improve GI cancer treatment, both in cells and mouse models.

The results showed that the drug combination killed liver and colorectal cancer cells more effectively than either drug alone. In animal models, mice with human liver tumors had slower tumor growth, without showing signs of weight loss or other toxicity. 

The researchers also found that aramchol and regorafenib work together to block important survival pathways inside cancer cells. This combination was especially effective in cells with a genetic variant called ATG16L1 T300, which is more common in people of African ancestry. The treatment triggered stress responses in the cancer cells and disrupted key proteins required for survival. It also activated autophagy, a natural recycling process that clears out damaged parts, eventually leading to cancer cell death.

“Aramchol interacted with the multi-kinase inhibitors sorafenib, regorafenib or lenvatinib, to kill GI tumor cells, with regorafenib exhibiting the greatest effect.”

Aramchol is currently in clinical trials for fatty liver disease and has a well-established safety profile, while regorafenib is already FDA-approved for cancer treatment. Together, their combination could advance fast into clinical testing for patients with GI cancers. However, researchers note that additional studies are needed to support the launch of early-phase clinical trials.

Altogether, this study may offer a more effective and less toxic alternative to current treatments for GI cancers. It also highlights the role of genetic variants in shaping treatment response, suggesting that future therapies could be more precisely tailored to each patient’s unique genetic profile.

DOI - https://doi.org/10.18632/oncotarget.28762

Correspondence to - Paul Dent - paul.dent@vcuhealth.org

Video short - https://www.youtube.com/watch?v=5saAqsqxi-Q

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Keywords - cancer, macroautophagy, flux; ER stress, aramchol, regorafenib

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Oncotarget

Aramchol Boosts Regorafenib Effectiveness in Gastrointestinal Tumors

BUFFALO, NY — August 21, 2025 — A new #research paper was #published in Volume 17, Issue 7 of Aging (Aging-US) on July 17, 2025, titled “The influence of cancer on a forensic age estimation tool.”

In this study by Charlotte Sutter, Daniel Helbling, Cordula Haas and Jacqueline Neubauer from the Zurich Institute of Forensic Medicine, University of Zurich and Onkozentrum Zurich, the researchers investigated how cancer might affect the accuracy of forensic tools used to estimate a person’s age from blood samples.

DNA methylation is a natural chemical modification of DNA that changes with age. Forensic scientists can use these changes to predict someone’s age from biological traces, such as blood found at a crime scene. However, medical conditions like cancer can alter these patterns and potentially reduce the accuracy of such predictions. This study investigated whether various cancer types influence the DNA markers used in age estimation.

“Our study is among the first to show whether it might be necessary to account for the influence of cancer on forensic age estimation tools in order to enhance estimation accuracy as much as possible.”

The researchers applied the VISAGE enhanced age estimation tool, a widely used DNA methylation-based method, to blood samples from 100 cancer patients and 102 healthy individuals. Age predictions in the control group were generally accurate, with small average errors. Patients with solid tumors, including breast and lung cancers, showed only slightly less accurate results. In contrast, individuals with blood cancers, particularly chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML), sometimes had large errors, with ages overestimated by as much as 50 years. 

Despite these few extreme cases, the study found that cancer does not typically have a strong impact on the accuracy of this forensic tool. Most cancer patients, even those undergoing treatment, had DNA methylation patterns similar to those of healthy individuals. The researchers found no consistent differences based on cancer type, stage, or treatment, except in isolated cases involving aggressive forms of cancer.

The findings support the continued use of current forensic age estimation methods. While aggressive cancers may occasionally affect prediction accuracy, such cases are rare. The researchers suggest noting these conditions as a possible factor in unusually large errors, without requiring changes to standard practice.

This study provides valuable information about how health conditions, such as cancer, may influence DNA-based age estimation. It strengthens confidence in the reliability of forensic age prediction tools, even when applied to individuals with a medical history of cancer.

DOI - https://doi.org/10.18632/aging.206281

Corresponding author - Cordula Haas - cordula.haas@irm.uzh.ch

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Keywords - aging, forensic age, estimation age prediction, cancer, DNA methylation, age acceleration

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Impact of Cancer on Forensic DNA Methylation Age Estimation

BUFFALO, NY — August 26, 2025 — A new #research paper was #published in Volume 17, Issue 7 of Aging (Aging-US) on July 21, 2025, titled “Association of DNA methylation age acceleration with digital clock drawing test performance: the Framingham Heart Study.”

In this study, led by first author Zexu Li from the Department of Anatomy and Neurobiology at Boston University Chobanian and Avedisian School of Medicine, and corresponding author Chunyu Liu from Boston University Chobanian and Avedisian School of Medicine and Boston University School of Public Health, researchers found that individuals with signs of faster biological aging had lower scores on a digital cognitive test taken seven years later. The findings suggest that the rate at which a person ages at the molecular level may be associated with how well their brain functions as they grow older.

Using data from the Framingham Heart Study, the researchers examined the relationship between biological aging and cognitive health. They used DNA methylation (DNAm) patterns—chemical changes that occur in the DNA with aging, known as epigenetic aging—to estimate biological age acceleration, and used the digital Clock Drawing Test (dCDT) to assess cognitive performance. The dCDT is a computerized version of a traditional pen-and-paper test that evaluates memory, thinking speed, and motor control. It provides an overall score and measures performance in specific areas such as spatial reasoning and movement.

Among 1,789 participants, higher levels of epigenetic age acceleration were associated with significantly lower cognitive scores, particularly those over age 65. Of all the epigenetic aging markers examined, the DunedinPACE measure showed the strongest association with reduced brain function in both younger and older adults. Other measures, such as Horvath and PhenoAge, were associated with lower scores only in older adults. Key areas affected included motor skills and spatial reasoning.

The researchers also studied blood-based protein markers used in an aging measure called GrimAge. Two proteins, PAI1 and ADM, were closely associated with lower cognitive scores, especially in older individuals. These results suggest that declines in brain and motor functions may reflect broader aging-related changes throughout the body.

“Digital cognitive measures displayed stronger associations with most DNAm aging metrics among older compared to younger participants, likely to reflect the cumulative and nonlinear age influences on both brain health and DNAm.”

This study supports the idea that epigenetic age may be a more accurate predictor of cognitive decline than chronological age. The dCDT, which is easy to use, automated, and more precise than traditional tools, may help detect early signs of brain aging. When combined with DNAm measures, it could become a valuable part of regular health screenings.

Overall, the findings provide strong evidence that faster biological aging is associated with cognitive decline. This research may lead to better ways of identifying and monitoring brain health in aging populations.

DOI - https://doi.org/10.18632/aging.206285

Corresponding author - Chunyu Liu - liuc@bu.edu

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Faster Biological Aging Linked to Cognitive Decline in Older Adults

Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality. While the development of targeted therapies has improved outcomes for many patients with EGFR-mutated NSCLC, those with rare EGFR variants often face limited treatment options, especially when the disease involves the central nervous system (CNS).

A recent research paper, titled “Durable complete response in leptomeningeal disease of EGFR mutated non-small cell lung cancer to amivantamab, an EGFR-MET receptor bispecific antibody, after progressing on osimertinib” published in Volume 16 of Oncotarget, describes a patient with NSCLC harboring two uncommon EGFR mutations—G719A and A289V—who experienced a prolonged and clinically significant response to amivantamab monotherapy, after prior treatments had failed.

Full blog - https://www.oncotarget.org/2025/08/26/amivantamab-monotherapy-in-rare-egfr-mutated-advanced-nsclc/

Paper DOI - https://doi.org/10.18632/oncotarget.28730

Correspondence to - Young Kwang Chae - young.chae@northwestern.edu

Video short - https://www.youtube.com/watch?v=UEiCz834a8c

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Keywords - cancer, amivantamab, monotherapy, rare EGFR mutation, NSCLC, leptomeningeal disease

About Oncotarget 

Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.

Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).

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Amivantamab Monotherapy in Rare EGFR-Mutated Advanced NSCLC

Aiden Deacon from the University of Minnesota-Twin Cities, Minneapolis, discusses a research paper he co-authored that was published in Volume 16 of Oncotarget, titled “Dissecting the functional differences and clinical features of R-spondin family members in metastatic prostate cancer.”

DOI - https://doi.org/10.18632/oncotarget.28758

Correspondence to - Justin Hwang - jhwang@umn.edu

Video interview - https://www.youtube.com/watch?v=OXKhWWU1gnY

Abstract

This study investigates the R-spondin family of genes (RSPO1/2/3/4), a group of secreted proteins that act as Wnt regulators, and their subsequent role in advanced prostate cancer (PC). When evaluating transcriptomic data from primary and metastatic PC patients, we found that alterations in RSPO2 were more prevalent than in other RSPO family members or Wnt-regulating genes APC and CTNNB1. Further, we found that RSPO2 alterations in PCs were significantly associated with worse disease-free survival. Through our in silico modeling, RSPO2 exhibited strong positive associations with genes regulating epithelial-mesenchymal transition (EMT) and double-negative prostate cancer (DNPC), but had negative correlations with androgen receptor (AR) and AR-associated genes. Furthermore, 3D modeling of RSPO2 revealed structural differences between itself and other RSPOs. In cell lines, RSPO2 overexpression caused up-regulation of EMT pathways, including EMT-regulatory transcription factors ZEB1, ZEB2, and TWIST1. Conversely, this was not observed when CTNNB1 was overexpressed in the same models. These findings highlight that, in PC, RSPO2 functions as a unique member of the R-spondin family by promoting genes and signaling pathways associated with aggressive PC, and RSPO2 amplifications are associated with poor outcomes in PC patients.

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Keywords - cancer, RSPO2, prostate cancer, Wnt signaling, genomics, therapeutics

About Oncotarget 

Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.

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Oncotarget author interview: Aiden Deacon

Behind the Study: R-spondin Family Roles in Metastatic Prostate Cancer

BUFFALO, NY — August 27, 2025 — A new #research paper was #published in Volume 17, Issue 7 of Aging (Aging-US) on July 24, 2025, titled “RNA-binding protein AUF1 suppresses cellular senescence and glycolysis by targeting PDP2 and PGAM1 mRNAs.”

In this study, Hyejin Mun, Chang Hoon Shin, Mercy Kim, Jeong Ho Chang, and Je-Hyun Yoon from the University of Oklahoma and Kyungpook National University investigated how changes in cellular metabolism contribute to aging. Their findings offer potential targets for therapies aimed at slowing or reducing the effects of aging.

As cells age, they often lose their ability to divide and begin releasing harmful signals that damage nearby tissues. This process, called cellular senescence, is linked to many age-related diseases. A key feature of senescent cells is their altered metabolism, where they use more glucose and oxygen, even when oxygen levels are low. This leads to the production of inflammatory substances and fatty acids, which can accelerate tissue damage. The study examined how these metabolic changes are controlled at the molecular level.

Researchers found that AUF1, a protein that binds to RNA, normally helps prevent aging by breaking down two enzymes involved in glucose metabolism: PGAM1 and PDP2. When AUF1 is missing or inactive, these enzymes build up. This causes the cell to produce more energy and inflammatory molecules, which are common features of senescent cells.

“Our high throughput profiling of mRNAs and proteins from Human Diploid Fibroblasts (HDFs) revealed that the expression of pyruvate metabolic enzymes is inhibited by the anti-senescent RNA-binding protein (RBP) AUF1 (AU-binding Factor 1).”

The team also identified another protein, MST1, which becomes active during cellular stress and aging. MST1 modifies AUF1 in a way that stops it from doing its protective job. As a result, PGAM1 and PDP2 accumulate, leading to faster aging of the cell. Experiments using human fibroblast cells and mouse models confirmed that higher levels of these enzymes are linked to stronger signs of cellular aging.

These findings improve our understanding of how metabolism affects the aging process. They highlight the MST1-AUF1-PDP2/PGAM1 pathway as a key factor in the metabolic shift seen in aging cells. Since these enzymes and proteins are already known to be involved in other diseases, existing or future therapies might be used to block this pathway and reduce the effects of aging.

This study offers a new direction for senotherapy—a field focused on treating or removing aging cells. By adjusting glucose metabolism through AUF1 and its targets, scientists believe it may be possible to slow aging or limit its effects on tissue function. More research is needed, but these insights could lead to new strategies for managing age-related diseases and promoting healthier aging.

DOI - https://doi.org/10.18632/aging.206286

Corresponding authors - Jeong Ho Chang - jhcbio@knu.ac.kr, and Je-Hyun Yoon - jehyun-yoon@ouhsc.edu

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Keywords - aging, AUF1, MST1, senescence, glycolysis

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AUF1 Protein Plays Anti-Aging Role by Regulating Cellular Metabolism

BUFFALO, NY – August 29, 2025 – A new #research paper was #published in Volume 16 of Oncotarget on August 29, 2025, titled “In vivo manipulation of the protein homeostasis network in rhabdomyosarcoma.”

In this study led by first author Kristen Kwong and corresponding author Amit J. Sabnis from the Department of Pediatrics, Division of Oncology, University of California San Francisco, researchers discovered that disrupting the protein quality control system in cancer cells slows tumor growth in rhabdomyosarcoma (RMS), the most common pediatric soft tissue cancer. This finding points to a new strategy for treating high-risk childhood cancers that often resist current therapies.

Rhabdomyosarcoma is a rare and aggressive cancer that primarily affects children and adolescents. Standard treatments like chemotherapy and radiation often have limited long-term success in high-risk cases. This study explored a different approach: targeting the cellular machinery that maintains protein quality, known as the proteostasis network. Cancer cells rely heavily on this system to survive stress caused by rapid growth and genetic instability.

“To examine whether MAL3-101 or more drug-like proteostasis inhibitors represent a new therapeutic strategy for RMS, we screened proteostasis components that might recapitulate the effects of MAL3-101 in vivo.”

The researchers first used a compound called MAL3-101 to disrupt protein control in RMS cells. They then identified which parts of the protein quality system were affected. Based on those findings, they searched for more drug-like compounds that could target the same pathways. 

They focused on a protein called p97, which plays a critical role in removing damaged or misfolded proteins. When they blocked p97 using a drug called CB-5083, the cancer cells could no longer manage internal stress and began to self-destruct. In both laboratory models and mice implanted with human RMS tumors, the treatment significantly slowed or stopped tumor growth. The drug triggered a stress response in the cells known as the unfolded protein response, which can lead to either recovery or programmed cell death.

However, not all tumors responded the same way. Some resisted the treatment by activating a backup system called autophagy, which allows cells to recycle parts of themselves under stress. By comparing tumors that responded well to those that did not, the researchers found that higher autophagy activity could serve as a warning sign for resistance. This insight may help identify which patients are more likely to benefit from therapies that target protein quality control.

While the results are promising, the drug’s effectiveness depended on the tumor’s genetic profile and how it handled stress. Combining p97 inhibition with other treatments or blocking alternative survival pathways like autophagy may improve outcomes. The researchers also noted the importance of developing safer and more targeted drugs to reduce side effects.

This study opens new possibilities for personalized cancer treatment, particularly for children with aggressive or relapsed RMS. By weakening the systems that cancer cells depend on to survive, rather than only using toxic treatments to kill them, scientists aim to develop more effective and less harmful therapies for young patients.

DOI - https://doi.org/10.18632/oncotarget.28764

Correspondence to - Amit J. Sabnis - amit.sabnis@ucsf.edu

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

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Blocking Protein Control Pathway Slows Rhabdomyosarcoma Growth in Mice

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