In this #episode of the Longevity & Aging Series, Dr. Shubhankar Suman from the Department of Oncology at Georgetown University Medical Center joins host Dr. Evgeniy Galimov to discuss a #research paper he co-authored in Volume 17, Issue 1 of Aging (Aging-US), titled: “Senolytic agent ABT-263 mitigates low- and high-LET radiation-induced gastrointestinal cancer development in Apc1638N/+ mice.”

DOI - https://doi.org/10.18632/aging.206183

Corresponding author - Shubhankar Suman - ss2286@georgetown.edu

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Video short - https://www.youtube.com/watch?v=M_WEht4vy4w

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Keywords - aging, senescence-associated secretory phenotype, senolytic agent, carcinogenesis, inflammation, β-catenin

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Aging (Aging-US)

Longevity & Aging Series (S3, E4): Dr. Shubhankar Suman

BUFFALO, NY - July 18, 2025 – A new #editorial was #published in Volume 16 of Oncotarget on July 16, 2025, titled “microRNAs in soft tissue sarcoma: State of the art and barriers to translation.”

In this article, Elizaveta K. Titerina, Alessandro La Ferlita, and Joal D. Beane from Ohio State University discuss the role of microRNAs in soft tissue sarcomas (STS), a rare and diverse group of cancers that begin in connective tissues, like bone or fat. The authors explain how these small molecules regulate cancer-related processes and highlight their potential as non-invasive biomarkers for diagnosis and monitoring. They also outline the main challenges that need to be addressed before microRNA-based strategies can be used in clinical settings.

Soft tissue sarcomas include over 50 subtypes, making precise diagnosis and effective treatment difficult. The editorial describes how microRNAs influence cancer growth, spread, and response to therapies. Because microRNAs are stable in body fluids like blood and saliva, they could be used for early detection and to help guide treatment decisions. Such as, certain groups of microRNAs are linked to how patients respond to specific drugs, showing their potential as tools for precision medicine.

“For example, miR-17-92 and miR-106b-25 clusters have been associated with sensitivity or resistance to eribulin in STS.”

The authors also explain that microRNAs could help distinguish between tumor types that are often difficult to differentiate, such as benign lipomas and malignant liposarcomas. Recognizing these differences is crucial for guiding treatment decisions. Specific patterns of microRNA expression in blood samples may enable clinicians to make quicker and more reliable diagnoses without the need for invasive procedures. Beyond their diagnostic role, microRNAs are also being explored as therapeutic tools, but applying microRNA-based therapies to patients remains challenging. These molecules can act as either cancer promoters or suppressors, depending on the environment, which complicates the development of safe and targeted treatments. However, new delivery methods such as lipid nanoparticles show promise in improving precision and safety.

Overall, microRNAs are emerging as an important focus in STS research, offering new possibilities for advancing diagnosis, prognosis, and treatment. As researchers continue to address the current challenges, these small molecules could become valuable tools in improving cancer care.

DOI - https://doi.org/10.18632/oncotarget.28754

Correspondence to - Joal D. Beane, joal.beane@osumc.edu

Video short - https://www.youtube.com/watch?v=MlLGA8BObPQ

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Keywords - cancer, soft tissue sarcoma, liposarcoma, microRNA, small non-coding RNA, cancer biomarkers

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Oncotarget

microRNAs Emerge as Biomarkers and Diagnostic Tools in Soft Tissue Sarcoma

BUFFALO, NY — July 21, 2025 — A new #research paper was #published in Aging (Aging-US) Volume 17, Issue 6, on June 27, 2025, titled “Enhancing oocyte activation in women with ovarian failure: clinical outcomes of the Stem Cell Regenera study using G-CSF mobilization of peripheral blood stem cells and intraovarian injection of stem cell factor-enriched platelet rich plasma in real-world-practice.”

This study, led by Amparo Santamaria with co-authors Ana Ballester and Manuel Muñoz from IVI Clinics Alicante, evaluates the effectiveness and safety of a regenerative treatment that may enable women with ovarian failure to regain the ability to produce viable eggs. The approach combines stem cell mobilization and enriched plasma injections into the ovaries to stimulate follicle growth. It provides an alternative for patients experiencing infertility due to poor ovarian response, diminished ovarian reserve, or premature ovarian insufficiency.

Researchers evaluated the Stem Cell Regenera treatment in 145 women, aged 26 to 44 years, who had not responded to conventional fertility therapies. The procedure involved mobilizing the body’s own stem cells using granulocyte colony-stimulating factor (G-CSF), followed by an injection of platelet-rich plasma enriched with stem cell factors directly into the ovaries. This method was designed to activate dormant follicles and promote ovarian regeneration.

Nearly 70% of participants demonstrated oocyte activation, defined as increased follicle growth or a rise in key hormone levels. Approximately 7% achieved spontaneous pregnancies, and 14% conceived through in vitro fertilization (IVF) after treatment. These results indicate that the therapy stimulates ovarian activity and may increase the chances of conception in selected patients.

“The primary outcome measures were the rate of oocyte activation, leukocytes and stem cell count, and pregnancy rates.”

No severe adverse effects were reported. Most participants tolerated the treatment well, with only mild and transient symptoms such as headaches or fatigue. The use of the patient’s own cells minimized the risk of immune reactions and helped ensure the treatment was safe.

The findings provide evidence of effectiveness and safety for the Stem Cell Regenera protocol in a clinical setting. While the study was retrospective observational, the outcomes support further investigation through larger controlled trials to confirm long-term benefits and identify which patient populations may gain the greatest benefit from this approach.

This research contributes to the growing field of regenerative medicine in reproductive health, offering clinicians additional tools to address infertility in women with complex ovarian conditions.

DOI - https://doi.org/10.18632/aging.206274

Corresponding author -Amparo Santamaria - Amparo.santamaria@ivirma.com

Author interview - https://www.youtube.com/watch?v=oRFJNwnXZWI

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Keywords - aging, Stem Cell Regenera, oocyte activation, ovarian regeneration, G-CSF, SCFE-PRP, ovarian failure

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Stem Cell Treatment Shows Potential for Restoring Fertility in Women with Ovarian Failure

A new #study published recently in Volume 17, Issue 6, examines a novel treatment for women with ovarian failure. Researchers from IVI Clinics Alicante in Spain investigated a procedure called Stem Cell Regenera, which uses the body’s own stem cells and platelet-rich plasma to activate dormant follicles in the ovaries. This innovative protocol could expand options for patients with ovarian failure who have not responded to conventional fertility therapies.

Understanding Ovarian Failure

Ovarian failure affects women’s ability to conceive by reducing the quantity and quality of eggs in the ovaries. Conditions like Poor Ovarian Response, Diminished Ovarian Reserve, and Premature Ovarian Insufficiency are key reasons for infertility and make it hard to use assisted reproduction methods like in vitro fertilization (IVF).

Standard fertility treatments often fail to improve outcomes for these patients, leaving donor eggs as the primary alternative. However, recent advances in regenerative medicine have raised the possibility of restoring ovarian function using cellular therapies. Emerging research suggests that the right biological conditions could reactivate dormant follicles within the ovaries, potentially helping patients to use their eggs.

Full blog - https://aging-us.org/2025/07/stem-cell-regenera-a-regenerative-approach-to-activating-dormant-ovarian-follicles/

Paper DOI - https://doi.org/10.18632/aging.206274

Corresponding author -Amparo Santamaria - Amparo.santamaria@ivirma.com

Author interview - https://www.youtube.com/watch?v=oRFJNwnXZWI

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Keywords - aging, Stem Cell Regenera, oocyte activation, ovarian regeneration, G-CSF, SCFE-PRP, ovarian failure

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Stem Cell Regenera: A Regenerative Approach to Activating Dormant Ovarian Follicles

BUFFALO, NY – July 22, 2025 – A new #research paper was #published in Volume 16 of Oncotarget on July 21, 2025, titled “Statins exhibit anti-tumor potential by modulating Wnt/β-catenin signaling in colorectal cancer.”

In this work, led by first author Sneha Tripathi from the Indian Institute of Science Education and Research and corresponding author Sanjeev Galande from the Center of Excellence in Epigenetics at Shiv Nadar University, researchers discovered that statins, widely used to lower cholesterol, may also suppress colorectal cancer growth. This finding highlights a potential new role for these common drugs in cancer prevention and therapy.

Colorectal cancer is one of the leading causes of cancer-related deaths worldwide, and new strategies are urgently needed to improve treatment results. Statins, originally developed to lower cholesterol levels, have gained attention for their possible anti-cancer properties. The study investigated how statins affect the Wnt/β-catenin signaling pathway, a critical driver in colorectal cancer development and progression.

The researchers discovered that statins disrupt the Wnt/β-catenin signaling pathway, leading to lower levels of tumor-promoting proteins and to cancer-suppressing cellular behaviors. Experiments in both colorectal cell cultures and mouse models confirmed that statins reduced tumor growth without causing noticeable side effects. This study further revealed that statins downregulate SATB1, a protein linked to aggressive tumor behavior, while increasing SATB2, a protein with tumor-suppressing effects. These changes made the cancer cells less able to grow and spread.

“This reciprocal regulation shifts cellular phenotypes between epithelial and mesenchymal states in 3D spheroid models.”

Overall, the findings suggest that statins could be repurposed to complement existing colorectal cancer treatments or even be used in preventive strategies for high-risk individuals. By targeting the molecular machinery that drives colorectal tumor development, statins offer a promising, accessible, and well-understood option for further research in cancer therapy.

This research opens the door to larger clinical studies to explore how best to integrate statins into cancer care. If successful, this approach could provide a cost-effective strategy for reducing the global burden of colorectal cancer, which remains a significant health challenge.

DOI - https://doi.org/10.18632/oncotarget.28755

Correspondence to - Sanjeev Galande - sanjeev.galande@snu.edu.in

Video short - https://www.youtube.com/watch?v=A95ICULaH3Y

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Keywords - cancer, colorectal cancer, statins, SATB1, Wnt/β-catenin signaling, tumor-suppressive phenotype

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Cholesterol-Lowering Drugs Show Promise Against Colorectal Cancer

BUFFALO, NY — July 23, 2025 — A new #research paper was #published in Aging (Aging-US) Volume 17, Issue 6, on June 16, 2025, titled “rDNA copy number variation and methylation from birth to sexual maturity.”

In this study, led by first authors Alina Michler and Sarah Kießling along with corresponding author Thomas Haaf from Julius Maximilians University in Germany, researchers explored how ribosomal DNA (rDNA) copy number and methylation change from infancy to adolescence. They discovered that the epigenetic changes often associated with aging in adults do not occur before sexual maturity. This finding offers new insights into when the biological aging process truly begins.

Ribosomal DNA plays a critical role in producing proteins essential for cell survival. The researchers analyzed blood samples from 280 individuals, ranging from newborns to 18 years of age, including healthy individuals and those with developmental delays. They measured the number of rDNA copies and examined how genes are switched on or off through methylation, a chemical modification of DNA. The results showed that while adults experience a gradual loss of active rDNA copies and increased methylation—a hallmark of aging—these changes were absent in children and teenagers. In fact, during childhood and adolescence, the number of active, unmethylated rDNA copies slightly increased.

These findings support the long-debated idea that biological aging begins only after the body reaches reproductive maturity. Until that point, cells appear to actively maintain rDNA in a youthful state, ensuring that protein production remains efficient. This may help explain why children and teenagers are better at resisting many age-related diseases and why their cells recover more easily from stress.

The study also shows that changes in rDNA copy numbers are not associated with unexplained developmental delays. This suggests these epigenetic processes are probably not involved in early-life syndromes. The findings highlight how the body works to preserve genetic stability during childhood and raise important questions about what triggers the shift to aging-related changes after puberty.

“Collectively our data suggest that the rDNA hypomethylation state is actively maintained in somatic tissues of young individuals.”

The insights gained from this research expand the understanding of the molecular clock of aging. They suggest potential new ways to delay aging processes by exploring how youthful rDNA methylation patterns are maintained. As scientists continue to investigate these mechanisms, the study provides a clear foundation for future research aimed at extending cellular health beyond adolescence.

DOI - https://doi.org/10.18632/aging.206271

Corresponding author - Thomas Haaf - thomas.haaf@uni-wuerzburg.de

Video short - https://www.youtube.com/watch?v=Ww21u33uUhk

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Keywords - aging, absolute rDNA copy number, active rDNA copy number, deep bisulfite sequencing, developmental delay, droplet digital PCR

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Ribosomal DNA Methylation Patterns Reveal When Aging Begins

BUFFALO, NY – July 24, 2025 – A new #casereport was #published in Volume 16 of Oncotarget on July 23, 2025, titled “Extracorporeal blood filtration leading to tumor growth arrest and reduced analgesic requirements in Stage IV poorly differentiated pancreatic adenocarcinoma: A case report.”

In this report, Susanna Ulahannan from the University of Oklahoma Health Sciences Center and colleagues describe the use of extracorporeal blood filtration in a patient with metastatic pancreatic cancer. The patient experienced clinical improvement, reduced pain, and no signs of new tumor growth over 12 months of follow-up.

Metastatic pancreatic cancer is difficult to treat and is often diagnosed at an advanced stage. In this case, a 51-year-old woman with stage IV poorly differentiated adenocarcinoma chose not to undergo standard chemotherapy. Instead, she received extracorporeal blood filtration with the Seraph® 100 device, which is designed to remove circulating tumor cells (CTCs) from the bloodstream. CTCs are thought to contribute to the spread of cancer to other organs.

“Circulating tumor cells (CTC’s) are tumor cells that are shed from the primary tumor and travel via blood or lymphatic system to form micro metastases in distant organs under a suitable environment.“

The patient received between nine and twelve treatments over the course of a year. These treatments were performed both abroad, where the device is approved for this use, and under a clinical protocol in the United States. Medical imaging showed that her disease remained stable, with no new metastases detected. She also reported improvements in appetite, energy levels, and pain control. Her opioid use was reduced by 90%.

Blood samples confirmed a drop in CTC levels after treatment. This observation supports the idea that removing CTCs might help limit cancer progression in some patients. However, given that this is a single case report, larger clinical studies are needed to evaluate the effectiveness of this approach.

The mechanism behind the patient’s pain relief is not fully understood. Authors suggest that it may be related to the reduction of tumor cells or inflammatory molecules in the blood. Researchers noted that pro-inflammatory cytokines, known to influence pain, could also have been affected by the filtration process.

This is the first documented case of stable disease and reduced symptoms following CTC filtration in advanced pancreatic cancer. While these findings should not be generalized, they highlight an approach outside standard protocols that should be further explored in clinical research. Future studies will be needed to determine whether this method can contribute to symptom management or disease control in other patients with metastatic pancreatic cancer.

DOI - https://doi.org/10.18632/oncotarget.28756

Correspondence to - Susanna Ulahannan - susanna-ulahannan@ouhsc.edu

Video short - https://www.youtube.com/watch?v=dro6iUGDrVQ

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Keywords - cancer, extracorporeal blood filtration, circulating tumor cells, metastatic pancreatic cancer, seraph 100, OncoBind

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Blood Filtration Stabilizes Advanced Pancreatic Cancer: A Case Report

BUFFALO, NY — July 28, 2025 — A new #research paper was #published in Aging (Aging-US) Volume 17, Issue 6, on June 13, 2025, titled “Development of a novel transcriptomic measure of aging: Transcriptomic Mortality-risk Age (TraMA).”

In this study, led by Eric T. Klopack from the University of Southern California, researchers created a new RNA-based aging measure that predicts health risks and mortality. This measure, called Transcriptomic Mortality-risk Age (TraMA), uses gene expression data to estimate a person’s biological aging. This finding offers a new and potentially more accurate way to track aging and understand health risks, especially for older adults.

Aging is a complex biological process that affects multiple systems in the body and increases the risk of disease and death. Scientists have long looked for reliable ways to measure biological aging. While DNA methylation and blood biomarkers are commonly used, this study focused on RNA—a molecule that reflects gene activity. By analyzing RNA sequencing data from nearly 4,000 U.S. adults aged 50 and older, the team developed TraMA to predict the probability of dying within four years.

TraMA proved to be a strong and independent predictor of early death, multiple chronic diseases, poor cognitive function, and difficulties with daily activities. It was also tested in another large group of long-lived families and in several smaller datasets from patients with conditions like diabetes, sepsis, and cancer. The results confirmed the tool’s usefulness across different populations and health conditions.

“TraMA was also externally validated in the Long Life Family Study and several publicly available datasets.”

Unlike earlier RNA-based aging measures, which were often built using small or non-representative samples, TraMA was developed using modern RNA sequencing technology results and a nationally representative dataset. This increases its reliability and potential for broad public health applications. The tool also demonstrated unique advantages over popular biological aging measures like GrimAge and PhenoAge, capturing distinct aspects of aging and health decline.

Importantly, TraMA tracks biological processes related to inflammation, immune function, and kidney and brain health, systems that play key roles in aging. It was also sensitive to behavioral and socioeconomic factors. For instance, smoking, obesity, and low physical activity were associated with older TraMA scores.

TraMA was also sensitive to changes in biological aging. In one study, researchers measured TraMA at two different time points and found that the more recent scores were better at predicting who would die. This suggests that TraMA can track changes in a person’s aging as their health evolves. It also performed well in both large-scale surveys and small clinical samples, making it a useful tool in many types of research.

By offering a new, accurate, and flexible method for measuring biological aging, TraMA may help researchers better understand how genes, lifestyle, and environment influence aging. This tool opens the door to more precise research on improving health and extending lifespan.

DOI - https://doi.org/10.18632/aging.206272

Corresponding author - Eric T. Klopack - klopack@usc.edu

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TraMA: New RNA-Based Measure Predicts Mortality Risk and Tracks Aging

BUFFALO, NY - July 29, 2025 – A new #research paper was #published in Volume 16 of Oncotarget on July 25, 2025, titled “Comprehensive genomic profiling of over 10,000 advanced solid tumors.”

In this study, led by Jean-Paul De La O from Exact Sciences Corporation, researchers analyzed data from over 10,000 solid tumor samples from patients with advanced cancer and found that more than 90 percent contained genetic changes that could guide treatment. This work demonstrates the growing impact of large-scale tumor DNA and RNA testing on patient care.

The researchers retrospectively analyzed OncoExTra assay information for 31 types of cancer, including breast, colorectal, prostate, lung, and ovarian cancers. Their analysis revealed that nearly a third of patients had alterations associated with approved drugs for their specific cancer, while another third had changes linked to therapies approved for other cancers. These results show that detailed genetic profiling could expand treatment choices.

“Biomarkers associated with on- or off-label FDA-approved therapies were detected in 29.2% and 28.0% of samples, respectively.”

Another relevant discovery was that many important mutations occurred at very low levels, which are often missed by simpler tests. By using a broad and highly sensitive approach, the scientists were able to identify these rare mutations. They also reported that 7.5 percent of samples carried gene fusions, unusual genetic events that can drive cancer growth. Such findings can be critical in selecting therapies that specifically target these abnormalities.

The study also highlighted the value of RNA sequencing in detecting fusion events that traditional DNA tests might miss. Prostate cancer and certain sarcomas showed particularly high rates of these fusion alterations. This type of information can refine cancer diagnosis and improve therapy planning.

In addition, the researchers identified changes in several major cancer-related pathways, including those that control cell growth, DNA repair, and immune system response. Alterations in these pathways can point to newer treatment options, such as immunotherapy or drugs designed to block specific cell signals.

Overall, this study shows that comprehensive genomic profiling can guide more personalized cancer care by identifying mutations, gene fusions, and other molecular patterns. Advanced testing methods like the OncoExTra assay reveal treatment opportunities even in advanced cancers, ensuring that subtle but important genetic changes are detected.

DOI - https://doi.org/10.18632/oncotarget.28757

Correspondence to - Jean-Paul De La O - jdelao@exactsciences.com

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Keywords - cancer, solid tumors, comprehensive genomic profiling, matched therapy, gene fusions, limit of detection

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Comprehensive Genomic Testing Reveals Treatment Targets in 90% of Advanced Solid Tumors

BUFFALO, NY — July 30, 2025 — A new #research paper was #published in Aging (Aging-US) on July 23, 2025, titled “Second generation DNA methylation age predicts cognitive change in midlife: the moderating role of childhood socioeconomic status.”

In this study, led by Sophie A. Bell and Eric Turkheimer from the University of Virginia, researchers investigated how biological aging, measured through DNA methylation, is connected to changes in thinking skills during midlife and whether childhood socioeconomic status influences this relationship. 

Biological age provides a picture of how the body is aging that goes beyond simply counting years. In this study, researchers used both first- and second-generation DNA methylation clocks—tools that track chemical changes in DNA as markers of aging. GrimAge and PhenoAge, the second-generation clocks designed to reflect broader health and aging processes, were more accurate at predicting long-term changes in Intelligence Quotient (IQ) than the first-generation models that only estimated chronological age. The study analyzed 287 participants from the Louisville Twin Study, which is a long-term project that has followed twins from childhood into midlife.

“DNAmAge was estimated with five commonly used algorithms, or epigenetic clocks (Horvath, Horvath Skin and Blood, GrimAge, and PhenoAge).”

The results showed that twins with more rapid epigenetic aging had a larger drop in IQ scores. This pattern remained even after considering genetic background and early family environment, made possible by the twin-based design. Importantly, the relationship was strongest in twins who had grown up in families with lower socioeconomic status. This finding suggests that early-life disadvantage may make individuals more vulnerable to the effects of biological aging on brain health.

This research adds knowledge to earlier work showing that childhood poverty can influence long-term health. It also highlights the value of second-generation epigenetic clocks as early indicators of brain aging. Unlike the first generation of clocks, these newer tools capture broader biological changes such as inflammation, disease risk, and behaviors like smoking.

Although smoking partly explained the results because it strongly influences DNA methylation, it did not fully account for the association between accelerated biological aging and cognitive decline. This suggests that both life experiences and lifestyle factors shape body and brain aging.

By combining decades of developmental data with a genetically informed twin design, the study provides new evidence that biological aging, especially when shaped by childhood adversity, is a key factor in midlife cognitive decline. These findings may inform early health strategies that consider both social and biological risks and support the use of second-generation methylation clocks to predict age-related cognitive changes.

DOI - https://doi.org/10.18632/aging.206284

Corresponding authors - Sophie A. Bell - bvf7pa@virginia.edu, and Eric Turkheimer - ent3c@virginia.edu

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Study in Twins Links Childhood Environment to Epigenetic Aging and Cognitive Decline

Prostate cancer is the second most diagnosed cancer among men worldwide and remains a leading cause of cancer-related death. While early forms of the disease can usually be treated successfully, advanced cases remain a major challenge. Scientists have now discovered a new potential way to slow the growth of advanced, treatment-resistant prostate cancer. These results were recently published in Volume 16 of Oncotarget by researchers from the University of Cincinnati College of Medicine.

Understanding Advanced Prostate Cancer

Early-stage prostate cancer can often be treated successfully. Most treatments work by lowering testosterone levels or blocking the hormone from activating the androgen receptor (AR), which drives cancer growth.

In some patients, however, the disease progresses to castration-resistant prostate cancer (CRPC). Even with drastic reductions in testosterone levels, the tumors continue to grow at this stage. CRPC is much more difficult to treat, and current therapies such as hormone blockers or chemotherapy typically extend life by only a few months.

One reason for this resistance is that cancer cells often switch to a different form of the androgen receptor called AR-V7. This variant remains permanently active, even without testosterone, making hormone-based drugs less effective. Because of this, new treatment strategies that work independently of hormone levels are needed.

The Study: Targeting a New Weakness in Prostate Cancer Cells

In the study titled “Targeting PCNA/AR interaction inhibits AR-mediated signaling in castration resistant prostate cancer cells,” researchers Shan Lu and Zhongyun Dong from the University of Cincinnati College of Medicine investigated a new way to block CRPC growth.

Full blog - https://www.oncotarget.org/2025/07/29/a-new-way-to-target-resistant-prostate-cancer-cells/

Paper DOI - https://doi.org/10.18632/oncotarget.28722

Correspondence to - Zhongyun Dong - dongzu@ucmail.uc.edu

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Keywords - cancer, PCNA, androgen receptor, PCNA inhibitors, AR splicing variants, CRPC

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A New Way to Target Resistant Prostate Cancer Cells

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