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BUFFALO, NY — December 30, 2025 — A new #research paper was #published in Volume 17, Issue 11 of Aging-US on November 26, 2025, titled “Epigenetic aging signatures and age prediction in human skeletal muscle.” In this study, first author Soo-Bin Yang and corresponding author Hwan Young Lee from Seoul National University College of Medicine investigated how DNA methylation patterns in skeletal muscle change with age. Their findings offer a new and highly accurate method for estimating a person's age, with potential applications in forensic science and aging research. Skeletal muscle is essential for movement, energy balance, and physical strength, functions that become more important to monitor as people age. This study improves our understanding of how muscle tissue changes over time at the molecular level. Unlike previous research, which mainly analyzed living individuals of European descent, this study used postmortem samples from an Asian population. “We analyzed DNA methylation profiles from 103 pectoralis major muscle samples from autopsies of South Korean individuals (18–85 years) using the Infinium EPIC array.” The researchers analyzed DNA from over 100 pectoralis major muscle samples taken from individuals aged 18 to 85. They identified 20 DNA methylation sites, called CpGs, that were strongly associated with age. These CpGs were found in genes involved in muscle function, stress response, metabolism, and age-related diseases. Using these markers, the team built two machine learning models to predict age: one using Next-Generation Sequencing (NGS) and another using Single Base Extension (SBE). Both models were highly accurate, with average prediction errors between 3.8 and 5.5 years. The new “epigenetic clocks” outperformed existing age-prediction models designed for other tissue types. However, when applied to cardiac and uterine muscle, these models showed much lower accuracy, reinforcing the need for tissue-specific approaches in molecular age estimation. Beyond predicting age, the study also provides insight into how DNA methylation may affect muscle aging. Several of the identified CpGs were located in regions that regulate gene expression, being associated with a reduction of it in older muscle samples. Some of the affected genes are associated with sarcopenia, an age-related loss of muscle mass and strength. Overall, this study introduces two reliable and cost-effective methods to estimate age from skeletal muscle, even when the DNA is partially degraded, making it especially useful in forensic settings. It also offers a path forward for developing future therapies that may slow age-related muscle decline and highlights how skeletal muscle aging can differ depending on population, tissue type, and anatomical location. DOI - https://doi.org/10.18632/aging.206341 Corresponding author - Hwan Young Lee - hylee192@snu.ac.kr Abstract video - https://www.youtube.com/watch?v=1i6Ua0cceMU Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206341 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, skeletal muscle, age, DNA methylation, next generation sequencing, single base extension To learn more about the journal, please visit https://www.Aging-US.com​​ and connect with us on social media at: Bluesky - https://bsky.app/profile/aging-us.bsky.social ResearchGate - https://www.researchgate.net/journal/Aging-1945-4589 Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ LinkedIn - https://www.linkedin.com/company/aging/ Reddit - https://www.reddit.com/user/AgingUS/ Pinterest - https://www.pinterest.com/AgingUS/ YouTube - https://www.youtube.com/@Aging-US Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY - December 17, 2025 – A new #research paper was #published in Oncotarget (Volume 16) on December 15, 2025, titled “Machine learning-based survival prediction in colorectal cancer combining clinical and biological features.” In this study, led by Lucas M. Vieira from the University of Brasília and the University of California San Diego, researchers used machine learning to predict survival in patients with colorectal cancer. They built a model by combining biological markers with clinical data. This approach could help improve prognosis and guide treatment strategies for one of the world's most common and deadly cancers. The team analyzed data from over 500 patients, using clinical details such as age, chemotherapy status, and cancer stage, along with molecular features like gene expression and microRNAs. Their goal was to improve how clinicians identify high-risk patients and make outcome predictions more precise. Researchers evaluated three different patient data scenarios using different machine learning techniques. The best-performing was an adaptive boosting model, which achieved 89.58% accuracy. This approach showed that integrating clinical and biological data led to significantly better predictions than using either data type alone. Among the biological markers, the gene E2F8 was consistently influential in all patient groups and is known to play a role in tumor growth. Other important markers included WDR77 and hsa-miR-495-3p, which are also associated with cancer development. Key clinical predictors included cancer stage, patient age, lymph node involvement, and whether chemotherapy was administered. “The proposed method combines biological and clinical features to predict patient survival, using as input data from patients from the United States, available in the TCGA database.” Unlike earlier models that relied on either clinical or molecular data alone, this study demonstrates the added value of combining both. Ensemble methods, which merge multiple learning algorithms, provided more stable and consistent results across all patient groups tested. These research findings could lead to new tools that help clinicians better predict how a patient's disease might progress or respond to treatment. The study also highlights the importance of collecting complete clinical information, such as lifestyle factors, which were missing from the dataset but could enhance future predictions. Overall, the study demonstrated how machine learning can support more accurate and personalized survival predictions in colorectal cancer. It also points to potential future research on markers like E2F8, which may be useful for monitoring or targeted therapy. DOI - https://doi.org/10.18632/oncotarget.28783 Correspondence to - Lucas M. Vieira - lvieira@health.ucsd.edu Abstract video - https://www.youtube.com/watch?v=cy7UL5ZUKuI Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28783 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, colorectal cancer, machine learning, feature selection, non-coding RNAs, genes To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us on social media: Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — December 16, 2025 — A new #research paper was #published in Aging-US on December 10, 2025, titled “Theobromine is associated with slower epigenetic ageing.” In this study, led by Ramy Saad from King's College London and Great Ormond Street Hospital for Children NHS Foundation Trust, alongside Jordana T. Bell from King's College London, researchers found that higher levels of theobromine, a natural compound found in cocoa, are associated with slower biological aging in humans. The findings suggest that theobromine may support healthy aging. Epigenetic aging refers to biological changes that affect how genes function over time. It is measured using blood-based markers such as DNA methylation and telomere length, which together provide a more accurate picture of aging than chronological age. In this work, researchers analyzed data from two large European studies. In 509 women from the TwinsUK cohort, they found that higher blood levels of theobromine were associated with slower aging, especially based on GrimAge, an epigenetic clock that predicts the risk of age-related disease and early death. The results were confirmed in 1,160 men and women from the German KORA study. “We initially tested for the association between six metabolites found in coffee and cocoa, and epigenetic measures of ageing in blood samples from 509 healthy females from the TwinsUK cohort (median age = 59.8, IQR = 12.81, BMI = 25.35).“ Importantly, theobromine's effects were independent of related compounds such as caffeine. Even after adjusting for these other substances and different lifestyle factors, the association with slower aging remained strong. The study also associated higher theobromine levels with longer telomeres, another marker of healthy aging. While theobromine is commonly found in cocoa and chocolate, the study does not suggest increasing chocolate intake. However, it highlights the potential of everyday dietary components such as theobromine to influence aging. These findings support growing evidence that certain plant-based compounds may play a role in promoting long-term health. By identifying a connection between theobromine and slower biological aging, the study opens new directions for research into nutritional strategies for healthy aging. DOI - https://doi.org/10.18632/aging.206344 Corresponding authors - Ramy Saad - ramy.saad@kcl.ac.uk, and Jordana T. Bell - jordana.bell@kcl.ac.uk Abstract video - https://www.youtube.com/watch?v=S0P1USM8L6E Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206344 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, theobromine, epigenetic aging, DNA methylation, metabolomics, nutrition To learn more about the journal, visit https://www.Aging-US.com​​ and connect with us on social media at: Bluesky - https://bsky.app/profile/aging-us.bsky.social ResearchGate - https://www.researchgate.net/journal/Aging-1945-4589 Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ LinkedIn - https://www.linkedin.com/company/aging/ Reddit - https://www.reddit.com/user/AgingUS/ Pinterest - https://www.pinterest.com/AgingUS/ YouTube - https://www.youtube.com/@Aging-US Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

Cancer treatment is moving toward a more precision-based approach, where therapies are guided not just by the tumor's location but also by its genetic features. Mutations in cancer cells can point to specific drugs that may be more effective for certain patients. However, detecting these mutations often requires broad and detailed analysis. This is where comprehensive genomic profiling becomes especially important. One of the main challenges in cancer care is that many existing genetic tools focus on only a limited number of mutations. As a result, some treatment opportunities may be missed. Certain mutations are also difficult to detect because they occur at low levels or exist in complex forms, such as gene fusions. Without advanced screening methods, these changes may go unnoticed. To address these challenges, researchers from Exact Sciences Corporation conducted a large-scale study using a broad genomic screening approach. The findings were recently published in the journal Oncotarget. Full blog - https://www.oncotarget.org/2025/12/15/comprehensive-genomic-profiling-in-cancer-insights-from-over-10000-tumors/ Paper DOI - https://doi.org/10.18632/oncotarget.28757 Correspondence to - Jean-Paul De La O - jdelao@exactsciences.com Abstract video - https://www.youtube.com/watch?v=awiRhDfiMTE Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28757 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, solid tumors, comprehensive genomic profiling, matched therapy, gene fusions, limit of detection To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh MEDIA@IMPACTJOURNALS.COM

Treating aggressive cancers that do not respond to standard therapies remains one of the most significant challenges in oncology. Among these are basal-like breast cancers (BLBC), which lack hormone receptors and HER2 amplification. This makes them unsuitable for many existing targeted treatments. As a result, therapeutic options are limited, and patient outcomes are often poor. One emerging strategy is to induce senescence, a state in which cancer cells permanently stop dividing but remain metabolically active. This approach aims to slow or stop tumor growth without killing the cells directly. Although promising, the clinical application of senescence-based therapies has been limited by several challenges. Senescence is typically identified using biomarkers such as p16, p21, and beta-galactosidase activity. However, these markers are often already present in aggressive cancers like BLBC (Sen‑Mark+ tumors), making it difficult to determine whether a treatment is truly inducing senescence or merely reflecting the tumor's existing biology. Moreover, conventional screening methods may mistake reduced cell growth for senescence, cell death, or temporary growth arrest, leading to inaccurate assessments. This is especially problematic in large-scale drug screening, where thousands of compounds must be evaluated quickly and reliably. To overcome these issues, researchers from Queen Mary University of London and the University of Dundee have developed a new machine learning–based method to improve the detection of senescence in cancer cells. Their findings were recently published in Aging-US. The Study: Developing the SAMP-Score The study, titled “SAMP-Score: a morphology-based machine learning classification method for screening pro-senescence compounds in p16-positive cancer cells,” was led by Ryan Wallis and corresponding author Cleo L. Bishop from Queen Mary University of London. This paper was featured on the cover of Aging-US Volume 17, Issue 11, and highlighted as our Editors' Choice. Full blog - https://aging-us.org/2025/12/using-machine-learning-to-identify-senescence-inducing-drugs-for-resistant-cancers/ Paper DOI - https://doi.org/10.18632/aging.206333 Corresponding author - Cleo L. Bishop - c.l.bishop@qmul.ac.uk Abstract video - https://www.youtube.com/watch?v=qXI_KI3EgHE Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206333 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, SAMP-Score, senescence, senescent marker positive cancer cells, Sen-Mark+, machine learning, pro-senescence, high-throughput compound screening To learn more about the journal, please visit https://www.Aging-US.com​​ and connect with us on social media at: Bluesky - https://bsky.app/profile/aging-us.bsky.social ResearchGate - https://www.researchgate.net/journal/Aging-1945-4589 Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@Aging-US LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

The paper featured on the cover of this issue of Aging-US, published on October 30, 2025, entitled “SAMP-Score: a morphology-based machine learning classification method for screening pro-senescence compounds in p16-positive cancer cells,” represents an important methodological and conceptual advance at the interface of senescence biology, imaging and drug discovery. In this study, led by first author Ryan Wallis and corresponding author Cleo L. Bishop (Queen Mary University of London), the authors introduce SAMP-Score, a machine-learning–based framework designed to identify bona fide senescence induction in cancer cells where canonical markers fail. This is a timely and much-needed contribution to the field. Therapy-induced senescence has emerged as a powerful strategy to restrain tumor growth, yet its reliable detection in cancer cells remains a major bottleneckIn these contexts, cells often already display features associated with cellular aging, rendering conventional senescence markers ambiguous or misleading. Distinguishing true senescence from toxicity, stress responses or baseline “aged” phenotypes is therefore a critical unmet need. Rather than relying on predefined molecular readouts, the authors take a different approach and train a machine-learning model to recognize senescence-associated morphological profiles (SAMPs) which are subtle but reproducible changes in cellular architecture captured through high-content microscopy. By learning directly from image-based phenotypes, SAMP-Score is able to identify senescence with a level of precision that is difficult to achieve using marker-based strategies alone. The strength of the platform demonstrated through a large-scale screen of over 10,000 novel chemical entities in p16-positive basal-like breast cancer cells. From this screen, the compound QM5928 emerged as a robust inducer of senescence across multiple cancer models, notably without inducing cytotoxicity. Importantly, QM5928 retains activity in cellular contexts that are resistant to CDK4/6 inhibition, including palbociclib-refractory, p16-high tumors. Mechanistically, the authors show that QM5928 promotes nuclear relocalization of p16, consistent with a functional engagement of cell-cycle arrest pathways. These nuanced phenotypic changes would likely have gone undetected without the resolution and discrimination provided by SAMP-Score, underscoring the platform's ability to separate true senescence from confounding cellular states. This work exemplifies how machine learning and quantitative imaging can be harnessed to solve long-standing problems in senescence research, moving the field beyond binary marker expression toward phenotype-driven classification. Beyond its immediate relevance for cancer therapy, SAMP-Score offers a broadly applicable framework for senescence-based screening efforts across biological contexts. DOI - https://doi.org/10.18632/aging.206333 Corresponding author - Cleo L. Bishop - c.l.bishop@qmul.ac.uk Abstract video - https://www.youtube.com/watch?v=qXI_KI3EgHE Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206333 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts To learn more about the journal, please visit https://www.Aging-US.com​​ and connect with us on social media at: Bluesky - https://bsky.app/profile/aging-us.bsky.social ResearchGate - https://www.researchgate.net/journal/Aging-1945-4589 Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@Aging-US LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

Colorectal cancer (CRC) remains the second leading cause of cancer-related deaths globally. While early detection significantly improves outcomes, many patients are diagnosed at advanced stages when treatment options are limited and relapse is common. To address this challenge, researchers are exploring whether existing drugs can be repurposed for cancer therapy, a strategy that could accelerate drug development while reducing associated costs and risks. One class of drugs under investigation is statins, commonly prescribed to reduce cholesterol and prevent cardiovascular disease. Several studies have observed a potential link between elevated cholesterol and increased CRC risk. Cholesterol may support tumor growth by promoting membrane synthesis and energy metabolism in rapidly dividing cells. Building on this connection, researchers from leading Indian institutions, including the Indian Institute of Science Education and Research and the Center of Excellence in Epigenetics at Shiv Nadar Institution of Eminence, investigated how statins influence CRC cells at the molecular level. Their goal was to determine whether these widely used drugs could have a therapeutic role in oncology. The Study: Investigating the Molecular Impact of Statins in CRC Cells The study, titled “Statins exhibit anti-tumor potential by modulating Wnt/β-catenin signaling in colorectal cancer,” was published in Oncotarget (Volume 16). Using a combination of lipidomics, transcriptomics, proteomics, and 3D tumor models, the researchers explored how two widely prescribed statins, atorvastatin and simvastatin, affect molecular pathways associated with CRC progression. This integrative, multi-omics strategy enabled tracing statin-induced effects across different layers of cellular function, linking lipid, transcript, and protein changes to pathway-level shifts. Full blog - https://www.oncotarget.org/2025/12/03/repurposing-statins-exploring-anti-tumor-effects-in-colorectal-cancer/ Paper DOI - https://doi.org/10.18632/oncotarget.28755 Correspondence to - Sanjeev Galande - sanjeev.galande@snu.edu.in Abstract video - https://www.youtube.com/watch?v=A95ICULaH3Y Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28755 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, colorectal cancer, statins, SATB1, Wnt/β-catenin signaling, tumor-suppressive phenotype To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — December 3, 2025 — A new #essay was #published in Volume 17, Issue 11 of Aging-US on November 19, 2025, titled “On the intergenerational transfer of ideas in aging and cancer research: from the hypothalamus according to V.M. Dilman to the mTOR protein complex according to M.V. Blagosklonny.” In this work, Aleksei G. Golubev from the N.N. Petrov National Medical Research Center of Oncology reflects on the legacy of two influential Russian scientists, Vladimir M. Dilman and his son Mikhail V. Blagosklonny, who each introduced groundbreaking ideas about aging and cancer. Drawing from his own experience working in Dilman's lab, Golubev explores how their ideas remain deeply relevant to today's scientific understanding. The essay connects Dilman's “elevation theory” with Blagosklonny's “hyperfunction theory,” two frameworks that challenge the conventional view of aging as a process of decline. Instead, both propose that aging results from continued biological processes that once supported growth but eventually become harmful when left unchecked. Dilman believed that aging begins with reduced sensitivity in the hypothalamus, a brain region that regulates the body's balance. This desensitization disrupts metabolism and hormone levels, setting the stage for many chronic illnesses. Decades later, Blagosklonny expanded on this idea at the molecular level. Central to his theory is the mTOR protein complex, which regulates growth and metabolism and is now a major focus in aging research. Golubev also explores the historical and personal connections between the two scientists. Dilman, an endocrinologist trained in the Soviet Union, and Blagosklonny, a molecular biologist educated during the post-Soviet period, represent two generations shaped by a shared scientific tradition. “Dilman's scientific legacy is not as well recognized as it should be, partly due to bias in citation practices.” The essay also draws attention to a troubling trend in science: the tendency to overlook early contributions, especially from non-Western scholars. Many of Dilman's insights, such as the connection between high blood sugar, insulin resistance, and cancer, have since been validated by modern tools, yet his work is rarely cited. Golubev points out how citation practices, language barriers, and historical isolation have contributed to this lack of recognition. Finally, Golubev encourages the scientific community to look back and acknowledge the foundational work that shaped modern aging science. It also highlights the importance of cross-generational knowledge in moving science forward. By tracing the intellectual journey from hormonal regulation in the brain to molecular pathways in cells, this essay demonstrated the relevance of old ideas in a new biological era. DOI - https://doi.org/10.18632/aging.206338 Corresponding author - Aleksei G. Golubev - lxglbv@rambler.ru Abstract video - https://www.youtube.com/watch?v=LvrdghTKGws Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206338 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, gerontology, history of science, hyperfunction, mTOR, hypothalamus, cancer, metabolism, immunity To learn more about the journal, please visit https://www.Aging-US.com​​ and connect with us on social media: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@Aging-US LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — November 25, 2025 — A new #research paper was #published in Volume 17, Issue 10 of Aging-US on October 13, 2025, titled “Hospitalization with infections and risk of Dementia: a systematic review and meta-analysis.” This large-scale meta-analysis, led by first author Wei Yu Chua from the National University of Singapore and corresponding author Eng-King Tan from the National Neuroscience Institute and Duke-NUS Medical School in Singapore, shows that adults hospitalized with infections have a significantly higher risk of developing dementia. The findings are especially important as global populations grow older and hospitalizations for infections increase, highlighting a potential new approach for dementia prevention. “Out of 1900 studies that were screened initially, 16 studies comprising 4,266,276 patients were included for analysis.” The researchers analyzed data from over 4 million individuals across 16 studies, making this study the most comprehensive review to date on the association between infection-related hospital stays and long-term brain health. The results showed that being hospitalized for an infection raised the risk of all-cause dementia by 83%. Among the types of infections studied, sepsis carried the highest risk, followed by pneumonia, urinary tract infections, and skin or soft tissue infections. The risk of developing vascular dementia was notably higher than that of Alzheimer's disease. One possible explanation for the association between infections and dementia is that infections trigger systemic inflammation that may reach the brain. Inflammatory molecules can cross the blood-brain barrier, potentially leading to the buildup of damaging proteins and the death of brain cells. This process may be more severe in older adults, whose immune systems are often slower to respond and recover. The study also suggests that even a single infection-related hospitalization can speed up cognitive decline, especially in individuals already at higher risk. Importantly, the risk of dementia was greatest within the first year following an infection but remained elevated for many years afterward. In fact, studies with follow-ups longer than a decade showed even stronger associations. These results suggest the need for early cognitive monitoring after hospital discharge, particularly in older adults recovering from infections. These findings have important implications for healthcare systems, particularly those serving aging populations, and underscore the lasting impact that infections can have on the brain. This research highlights the importance of looking beyond genetics and lifestyle for prevention strategies. With over 50 million people affected by dementia worldwide and annual care costs in the U.S. exceeding $300 billion, identifying new and preventable risk factors is critical. Reducing infections, improving hospital care, and monitoring brain health after illness may offer promising ways to protect cognitive function in aging populations. DOI - https://doi.org/10.18632/aging.206329 Corresponding author - Eng-King Tan - tan.eng.king@singhealth.com.sg Abstract video - https://www.youtube.com/watch?v=uyv5VHHHIA4 Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206329 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts To learn more about the journal, visit https://www.Aging-US.com​​ and connect with us on social media at: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@Aging-US LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

Interest in healthier, longer lives is rising, supported by recent scientific advances in aging research. But turning those discoveries into everyday healthcare solutions remains a work in progress. In this landscape, longevity clinics have attracted attention as personalized alternatives to traditional medicine. What Are Longevity Clinics? Longevity clinics are private centers offering tailored programs designed to improve long-term health and slow biological aging. Using advanced diagnostics such as genetic sequencing, full-body imaging, and blood tests, they develop personalized plans that may include exercise, nutrition, hormone therapy, or experimental treatments. Frequently found in countries like the United States, Switzerland, and the United Arab Emirates, these clinics reflect a growing global interest in preventive healthcare, though their high costs and scientific credibility remain subjects of debate. The Editorial “Longevity clinics: between promise and peril,” an editorial by 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), was published in Aging-US (Volume 17, Issue 10). Full blog - https://aging-us.org/2025/11/longevity-clinics-balancing-innovation-with-regulation/ Paper 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 Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206330 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, longevity clinics, biomarkers, frailty, senescence To learn more about the journal, visit https://www.Aging-US.com​​ and connect with us on social media at: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@Aging-US LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — November 20, 2025 — A new #research paper was #published in Volume 17, Issue 10 of Aging-US on October 10, 2025, titled “Developmental arrest rate of an embryo cohort correlates with advancing reproductive age, but not with the aneuploidy rate of the resulting blastocysts in good prognosis patients: a study of 25,974 embryos.” In this large-scale study, Andres Reig of the IVIRMA Global Research Alliance and Robert Wood Johnson Medical School, along with Emre Seli of the IVIRMA Global Research Alliance and Yale School of Medicine, investigated how female age and chromosomal abnormalities affect embryo development in patients undergoing in vitro fertilization (IVF). They found that embryo developmental arrest (EDA) becomes more common as women age. However, this arrest is not directly associated with the presence of chromosomal errors in the embryos that continue to develop. These findings could help improve fertility counseling and treatment strategies. The researchers analyzed 25,974 embryos from 1,928 IVF cycles, all from patients with a good chance of success. The study showed that the percentage of embryos that stopped developing before reaching the blastocyst stage increased with age: from 33% in women under 35 to 44% in those over 42. Despite this rise, the rate of chromosomal abnormalities, known as aneuploidy, in the embryos that did reach the blastocyst stage did not show a strong connection with the rate of arrest after adjusting for age. This distinction is important because both developmental arrest and aneuploidy reduce the number of embryos suitable for transfer. But this study suggests they are caused by different biological processes. In other words, an embryo may stop developing even if it has the correct number of chromosomes, and some embryos with chromosomal abnormalities may still grow to the blastocyst stage. “A very weak positive correlation was identified between EDA rate and the rate of aneuploidy (r: 0.07, 95% CI 0.03–0.11; R2: 0.00, p < 0.01) when evaluating all cohorts.” The authors suggest that other factors, such as the health of the egg's mitochondria or mutations in maternal-effect genes, may explain why some embryos stop developing. These insights could help researchers identify new ways to improve embryo quality, especially for older women undergoing IVF. Importantly, the study focused on embryos that developed far enough to be tested, which helped avoid technical problems that come with analyzing arrested embryos directly. This approach allowed for more reliable comparisons across age groups and embryo quality. Overall, the study highlights the importance of maternal age as a key factor in embryo development, independent of chromosomal results. It also opens new directions for research, aiming to better understand why embryos fail to develop and how this knowledge might lead to improved fertility treatments in the future. DOI - https://doi.org/10.18632/aging.206328 Corresponding author - Emre Seli - emre.seli@yale.edu Abstract video - https://www.youtube.com/watch?v=g0oS3HBNmuQ Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206328 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, ovarian aging, reproductive aging, embryonic arrest, embryonic aneuploidy, developmental arrest To learn more about the journal, please visit https://www.Aging-US.com​​ and connect with us on social media: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@Aging-US LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

Cancer is a disease caused by the uncontrolled growth of cells that escape the body's natural defenses. One way cancer protects itself is by taking advantage of certain immune cells called regulatory T cells, or Tregs. Normally, Tregs help prevent autoimmune diseases by controlling the immune system. But inside tumors, they behave differently. Instead of defending the body, they suppress the immune cells that could attack the cancer. Many cancer treatments aim to activate the immune system to fight tumors more effectively. However, the presence of Tregs within the tumor makes this difficult. These cells act like bodyguards for the cancer, blocking the immune response that might otherwise slow or stop tumor growth. Researchers have tried to eliminate Tregs by targeting a protein called CD25, found on their surface. However, earlier efforts often failed because these treatments also interfere with interleukin-2 (IL-2), a molecule that is essential for other immune cells to function. Blocking IL-2 weakens the entire immune response, limiting the treatment's effectiveness. To overcome this challenge, scientists recently developed a new antibody called 2B010. This study, titled “A novel anti-human CD25 mAb with preferential reactivity to activated T regulatory cells depletes them from the tumor microenvironment,” was published in Oncotarget (Volume 16). Full blog - https://www.oncotarget.org/2025/11/19/new-antibody-removes-tregs-to-boost-immune-response-against-cancer/ Paper DOI - https://doi.org/10.18632/oncotarget.28752 Correspondence to - Ethan M. Shevach - eshevach@Niaid.NIH.gov Abstract video - https://www.youtube.com/watch?v=2NJcGsI7WXA Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28752 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, Treg, CD25, TME, mAb, GVHD To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY – November 18, 2025 – A new #review was #published in Oncotarget (Volume 16) on November 14, 2025, titled “Mechanism of anticancer action of bifidobacterium: Insights from gut microbiota.” This review, led by first author Hoang Do and correspondent author Ashakumary Lakshmikuttyamma from Thomas Jefferson University, explores how bifidobacterium, a common probiotic found in the gut, may contribute to cancer prevention and therapy. By analyzing existing studies, the authors highlight the growing importance of gut health in cancer treatment and shed light on how bifidobacterium could complement standard cancer therapies. Bifidobacterium is widely known for promoting digestive health and is often included in fermented foods and dietary supplements. However, emerging evidence suggests it may also play a broader role in immune regulation and cancer defense. The review explains how certain strains of bifidobacterium may enhance the effectiveness of chemotherapy, radiation, and immunotherapy in cancers such as breast, lung, colorectal, and gastric cancers. According to the review, bifidobacterium influences cancer outcomes through several biological mechanisms. It helps regulate immune function by reducing inflammation and supporting the activity of immune cells that target tumors. For instance, strains like B. longum and B. breve have been shown to lower levels of harmful inflammatory markers and boost anti-inflammatory responses. These changes can make cancer treatments more effective while also reducing side effects. “Presence of Bifidobacterium breve in gut microbiota extended the median progression-free survival of NSCLC patients.” The review also discusses how bifidobacterium helps detoxify the body by breaking down cancer-causing compounds and limiting their ability to damage cells. In preclinical studies, the probiotic reduced the activity of enzymes that produce carcinogens and helped in converting food-based substances into cancer-fighting agents. Some strains were even found to suppress genes that promote tumor growth and increase molecules that trigger cancer cell death. The authors emphasize that diet plays a critical role in supporting the growth of bifidobacterium. Foods rich in dietary fiber, especially those containing inulin and oligosaccharides like garlic, onions, or leeks, can help increase its levels in the gut. This suggests that simple dietary changes could not only improve gut health but also support cancer prevention and treatment strategies. Although the review presents compelling evidence, the authors stress the need for more clinical trials to determine how different strains of bifidobacterium affect specific types of cancer. Personalized approaches may be necessary to match the right probiotic strains with individual treatment plans. As research continues to uncover the link between gut microbes and cancer, bifidobacterium stands out as a promising natural ally that could enhance the body's defenses and improve cancer treatment outcomes. DOI - https://doi.org/10.18632/oncotarget.28779 Correspondence to - Ashakumary Lakshmikuttyamma - axl025@jefferson.edu Abstract video - https://www.youtube.com/watch?v=KTWJDAN15lY Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28779 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — November 18, 2025 — A new #research paper was #published in Volume 17, Issue 10 of Aging-US on October 3, 2025, titled “Growth hormone excess drives liver aging via increased glycation stress.” In this study, led by first author Parminder Singh alongside with corresponding authors Pankaj Kapahi from the Buck Institute for Research on Aging and Andrzej Bartke from Southern Illinois University School of Medicine, researchers investigated how elevated growth hormone (GH) levels contribute to liver aging and dysfunction. They found that excess GH disrupts liver metabolism in ways that resemble aging-related liver damage. The study suggests that managing glycation stress may help prevent or treat liver diseases linked to abnormal hormone levels. Excess GH is known to cause different disorders, but its long-term impact on internal organs like the liver has remained unclear. To address this, researchers used a mouse model engineered to overproduce bovine GH and examined how chronic hormone exposure affects liver function over time. “Pathological conditions such as acromegaly or pituitary tumors result in elevated circulating GH levels, which have been implicated in a spectrum of metabolic disorders, potentially by regulating liver metabolism.” The team found that young mice with GH overexpression showed molecular and cellular patterns similar to those in naturally aged livers. In both groups, genes involved in metabolism were suppressed, while those linked to immune and inflammatory responses were activated. On one hand, the metabolic changes were associated with the buildup of advanced glycation end products, harmful compounds formed when sugars attach to proteins or fats without proper regulation. On the other hand, the immune and inflammatory changes reflected a process known as “inflammaging,” a form of chronic, low-grade inflammation commonly associated with aging. By revealing the overlap between hormone-driven and age-related liver dysfunction, the study provides new insight into how GH may accelerate aging processes. Importantly, the team showed that reducing glycation stress can reverse many of these negative effects. Mice treated with a compound that lowers glycation levels demonstrated improved liver health, reduced insulin resistance, and enhanced physical function. This intervention also corrected several abnormal genetic patterns caused by excess GH. The findings point to a potential therapeutic strategy for liver diseases associated with aging and hormonal imbalances. Overall, this research identifies glycation and its byproducts as key contributors to liver damage caused by excess GH. It suggests that targeting glycation could offer broad therapeutic benefits, not only for hormone-related conditions but also for supporting liver health during aging. DOI - https://doi.org/10.18632/aging.206327 Corresponding authors - Andrzej Bartke - abartke@siumed.edu and Pankaj Kapahi - pkapahi@buckinstitute.org Abstract video - https://www.youtube.com/watch?v=6v8xi5muLwA Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206327 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, growth hormone, glycation stress, Gly-Low To learn more about the journal, visit https://www.Aging-US.com​​ and connect with us on social media at: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@Aging-US LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

In this episode of the Longevity & Aging Series, Dr. Amparo Santamaria from the Reproductive Hematology Unit at the IVIRMA Alicante Clinic in Spain joins Dr. Evgeniy Galimov to discuss her #research paper #published in Volume 17, Issue 6 of Aging-US, 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.” DOI - https://doi.org/10.18632/aging.206274 Corresponding author - Amparo Santamaria - Amparo.santamaria@ivirma.com Video interview - https://www.youtube.com/watch?v=Zlezd0x_EJQ Longevity & Aging Series - www.aging-us.com/longevity Abstract The study assesses the effectiveness and safety of the Stem Cell Regenera Treatment for oocyte activation in women with ovarian failure, including conditions such as Poor Ovarian Response (POR), Diminished Ovarian Reserve (DOR), and Premature Ovarian Insufficiency (POI). This retrospective observational study was conducted from January 2023 to December 2024 at the IVIRMA Alicante Clinics in Spain. Women diagnosed with ovarian failure participated in the study, which involved mobilizing Hematopoietic Stem Cells from bone marrow into peripheral blood using granulocyte colony- stimulating factor (G-CSF). This was followed by an intraovarian injection of Stem Cell Factor- enriched Platelet Rich Plasma (SCFE-PRP). The primary outcome measures were the rate of oocyte activation, leukocytes and stem cell count, and pregnancy rates. Oocyte activation was defined as an increase in total Antral Follicle Count of three or more follicles after treatment and/or at least a 20% rise in Anti-Müllerian Hormone levels. Safety was assessed based on adverse effects. Pregnancy rates were evaluated for both spontaneous gestation and following in vitro fertilization (IVF) treatment. A total of 145 women participated: the overall activation rate was 68.28%, with 7.07% achieving spontaneous gestation and 14.14% achieving pregnancy following IVF. Mobilization of CD34+ cells was successful in all participants, with an average collection of 32.96 CD34+ cells/μl. No severe adverse effects were observed. The study concluded that the Stem Cell Regenera Treatment is effective and safe for oocyte activation in women with ovarian failure in real-world practice. Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206274 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, Stem Cell Regenera, oocyte activation, ovarian regeneration, G-CSF, SCFE-PRP, ovarian failure To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us on social media at: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@Aging-US LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY - November 12, 2025 – A new #research paper was #published in Oncotarget (Volume 16) on November 6, 2025, titled “LRIG1-3 in gliomas: LRIG1 protein expression decreased in higher grade gliomas.” In this study by Marlene Happe, Saskia Kuhl, Lukas Görtz, Roland Goldbrunner and Marco Timmer, from the University of Cologne, researchers found that the LRIG1 protein, which may help suppress tumors, is present at lower levels in more aggressive gliomas, a type of brain tumor. The findings suggest that LRIG1 could serve as a useful marker for tumor severity and potentially as a target for future therapies. Gliomas are the most common malignant brain tumors in adults and carry a poor prognosis, particularly in their most severe form, glioblastoma. This study investigated three related proteins: LRIG1, LRIG2, and LRIG3, which are involved in regulating cell growth signals. While LRIG1 and LRIG3 have shown tumor-suppressing effects in previous studies, LRIG2 is thought to support tumor growth. The researchers analyzed tumor samples from patients to understand how these proteins behave across different glioma grades and how they respond to chemotherapy. The results showed that LRIG1 protein levels decline significantly as tumor grade increases. Low-grade gliomas displayed much higher LRIG1 expression than high-grade tumors. Among high-grade tumors, primary glioblastomas had the lowest levels of LRIG1. Interestingly, secondary glioblastomas, which typically develop from lower-grade tumors, had higher levels of LRIG1 than primary glioblastomas. This difference may contribute to their relatively better clinical outcomes. These results highlight LRIG1's potential role in slowing tumor progression. In contrast, LRIG2 showed a more complex pattern. While its gene expression was higher in lower-grade tumors, the actual protein levels were slightly elevated in higher-grade ones, which are more aggressive. This mismatch suggests that processes occurring after gene transcription may influence how much LRIG2 protein is produced. “However, our data on LRIG2 indicate that its role in glioma may be more complex than previously thought, warranting further investigation.” Concerning LRIG3, it was found in higher amounts in glioma tissue compared to surrounding healthy tissue. Its expression was particularly high in low-grade tumors. However, chemotherapy did not consistently affect LRIG3 levels, and results varied depending on tumor type and treatment status. Overall, the study suggests that members of the LRIG protein family, especially LRIG1, could serve as important biomarkers to distinguish between glioma types and grades. Although chemotherapy did not significantly change their expression in most cases, these proteins have high potential as diagnostic tools or therapeutic targets. Further research is needed to better understand their roles in glioma development and treatment response. DOI - https://doi.org/10.18632/oncotarget.28775 Correspondence to - Marco Timmer - marco.timmer@uk-koeln.de Abstract video - https://www.youtube.com/watch?v=ZHsKLBEyBbM Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28775 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, oncology, glioma, glioblastoma, LRIG1, LRIG2, LRIG3 To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh MEDIA@IMPACTJOURNALS.COM

Synucleinopathies are a group of age-related neurological disorders, including Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. Most individuals are not diagnosed until these diseases have significantly progressed, as early symptoms, such as a reduced sense of smell, subtle cognitive or motor changes are too vague to serve as reliable indicators. To uncover specific biological signs that appear earlier and clearly point to the disease process, researchers from Saarland University developed a study titled “Brain region-specific and systemic transcriptomic alterations in a human alpha-synuclein overexpressing rat model,” featured as the cover Aging-US, Volume 17, Issue 10. Full blog - https://aging-us.org/2025/11/alpha-synuclein-overexpression-in-rats-reveals-early-clues-to-synucleinopathies/ Paper DOI - https://doi.org/10.18632/aging.206331 Corresponding author - Thomas Hentrich - thomas.hentrich@uni-saarland.de Abstract video - https://www.youtube.com/watch?v=Yl6AfVchkb0 Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206331 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, alpha-synuclein, transgenic rat model, different brain regions, transcriptome analysis To learn more about the journal, please visit https://www.Aging-US.com​​ and connect with us on social media at: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@Aging-US LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

Prostate cancer is one of the most common cancers in men. While treatment options have improved, advanced stages of the disease remain difficult to manage. One promising approach involves a process called ferroptosis. This is a type of programmed cell death that relies on iron and lipid oxidation to kill cancer cells by damaging specific fats in their outer membrane. These fats are especially vulnerable in environments with normal oxygen levels. However, many prostate tumors grow in low-oxygen areas of the body, a condition known as hypoxia, where ferroptosis becomes less effective. A recent study, titled “Hypoxia induced lipid droplet accumulation promotes resistance to ferroptosis in prostate cancer,” and published on Oncotarget (Volume 16), explores how oxygen-poor environments help prostate cancer cells resist treatment and what strategies could help overcome this resistance. Full blog - https://www.oncotarget.org/2025/11/06/how-low-oxygen-shields-prostate-cancer-from-ferroptosis-therapies/ Paper DOI - https://doi.org/10.18632/oncotarget.28750 Correspondence to - Noel A. Warfel - warfelna@arizona.edu, and Shailender S. Chauhan - shailenderc@arizona.edu Abstract video - https://www.youtube.com/watch?v=xFypDT4ALmc Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28750 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, hypoxia, lipid droplets, ferroptosis, resistance, prostate To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — November 3, 2025 — A new #research paper featured on the #cover of Volume 17, Issue 10 of Aging-US was #published on October 20, 2025, titled “Brain region-specific and systemic transcriptomic alterations in a human alpha-synuclein overexpressing rat model.” In this study, led by first author Vivien Hoof and corresponding author Thomas Hentrich from Saarland University, Germany, researchers investigated how excess alpha-synuclein—a protein linked to Parkinson's disease—affects gene activity in different brain regions and the gut. They found that early, region-specific gene disruptions may contribute to the appearance of disease, with some effects also detected in the gut. These early molecular changes could serve as biomarkers for Parkinson's and point to new directions for treatment. Alpha-synuclein accumulates in the brains of individuals with Parkinson's disease and other age-related neurological conditions known as synucleinopathies. To better understand this process, the research team used a genetically modified rat model that overexpresses human alpha-synuclein. They studied gene expression in the striatum, cortex, and cerebellum—three key brain regions involved in movement and cognition—and analyzed how these changes evolved with age. “Transcriptomic analyses were performed on gene and transcript level of striatal, frontocortical, and cerebellar tissue in 5- and 12-month-old transgenic (BAC SNCA) and wild type rats […]” The results showed that gene alterations appeared earlier and were more pronounced in young rats, particularly in the striatum and cortex, before any visible signs of disease manifested. This early disruption challenges the common belief that gene alterations gradually increase with age and suggests that early-life molecular changes may be critical in disease development. The researchers also found that many gene expression changes were unique to individual brain regions. However, they identified a set of genes that were consistently affected across all brain regions and the gut. This suggests that the disease may begin to affect the entire body—not just the brain—long before symptoms become noticeable. Several of the shared genes are involved in synaptic signaling and inflammation—processes known to be altered in Parkinson's. Others are linked to dopamine production and neuronal plasticity, indicating potential early efforts by the brain to compensate for the harmful effects of the alpha-synuclein buildup. Overall, this study provides a detailed view of how alpha-synuclein affects gene networks early in the disease process. Understanding these changes may help identify biomarkers and develop targeted therapies before irreversible brain damage occurs. DOI - https://doi.org/10.18632/aging.206331 Corresponding author - Thomas Hentrich - thomas.hentrich@uni-saarland.de Abstract video - https://www.youtube.com/watch?v=Yl6AfVchkb0 Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206331 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, alpha-synuclein, transgenic rat model, different brain regions, transcriptome analysis To learn more about the journal, please visit https://www.Aging-US.com​​ and connect with us on social media at: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@Aging-US LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

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 Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206320 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, Trf1, metabolism, leaner, fat, telomeres To learn more about the journal, visit https://www.Aging-US.com​​ and connect with us on social media at: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

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 Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28742 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, Blastic plasmacytoid dendritic cell neoplasm (BPDCN), Next-generation sequencing (NGS), CCDC50 To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh MEDIA@IMPACTJOURNALS.COM

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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 Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206316 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - cell senescence, aging, Runx1, nucleus pulposus, intervertebral disc degeneration To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us on social media at: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@Aging-US LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

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 Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28770 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, oncology, amplitude-modulated radiofrequency electromagnetic fields, glioblastoma, TheraBionic, CACNA1H, Cav3.2 To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh MEDIA@IMPACTJOURNALS.COM

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 Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206313 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, glycocalyx, hyaluronan To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us on social media at: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

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 Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206310 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, aging, environmental enrichment, working memory, complex cognition, immediate early genes To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us on social media at: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

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

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 Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28737 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, HER2 mutation, NSCLC, lung cancer, targeted therapy, genomic profiling To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh MEDIA@IMPACTJOURNALS.COM

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. Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206308 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, prediabetes, social determinants of health, health equity, cardiovascular health, population health To learn more about the journal, visit https://www.Aging-US.com​​ and connect with us on social media at: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — October 7, 2025 — A new #research paper was #published in Volume 17, Issue 9 of Aging-US on August 27, 2025, titled, “Deregulated miR-145 and miR-27b in Hutchinson-Gilford progeria syndrome: implications for adipogenesis.” In this study, led by first author Felix Quirin Fenzl and corresponding author Karima Djabali from the Technical University of Munich (TUM), researchers identified that miR-145-5p and miR-27b-3p interfere with the formation of fat cells in children with Hutchinson-Gilford progeria syndrome (HGPS), a rare and fatal premature aging disorder. Their findings help explain why patients often experience fat loss and related metabolic complications and suggest new potential therapeutic strategies. Hutchinson-Gilford progeria syndrome is a genetic condition that causes rapid aging in children, often leading to early death due to heart disease. Although affected children appear healthy at birth, they soon develop signs of accelerated aging, including hair loss, stiff joints, and a significant reduction in fat tissue. While certain treatments can slow disease progression, many aspects, such as the loss of fat tissue, remain poorly understood. “Overall, this study provides the first comprehensive miRNA profiling of HGPS and control fibroblasts across different stages of cellular senescence.” This study focused on how microRNAs—tiny molecules that help regulate gene expression—contribute to the disease. To explore this, the researchers used skin-derived stem cells from both healthy individuals and HGPS patients. When they transformed these cells into fat cells, the HGPS-derived stem cells formed significantly fewer fat cells. This difference was linked to unusually high levels of miR-145-5p and miR-27b-3p. These molecules were found to silence important genes required for fat cell growth and function. When the researchers blocked these microRNAs, fat cell formation improved. The team also examined fat tissue from a mouse model of HGPS. Similar to the human cells, these mice showed increased levels of miR-145-5p and miR-27b-3p and impaired fat development. These results confirm that these two microRNAs play a central role in the loss of fat tissue seen in the disease. Importantly, reducing their activity could become a promising therapeutic strategy for restoring fat tissue in affected individuals. Although further research is needed before developing treatments, this study represents a step forward in understanding the molecular causes of lipodystrophy, a condition in which the body cannot form healthy fat tissue, in HGPS. It also opens the door for future therapies that could improve quality of life and health outcomes for patients. In the long term, similar approaches might benefit people with other metabolic diseases, such as obesity or diabetes, where fat cell function is also disrupted. DOI - https://doi.org/10.18632/aging.206309 Corresponding authors - Karima Djabali — djabali@tum.de Abstract video - https://www.youtube.com/watch?v=b0ksC3cvdZ0 Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206309 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, Hutchinson-Gilford progeria syndrome (HGPS), progerin, microRNAs, adipogenesis To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us on social media at: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — October 3, 2025 — A new #research perspective was #published in Volume 17, Issue 9 of Aging-US on August 26, 2025, titled “Analysis of the current state of frailty indexes and their implementation for aging intervention studies.” In this work, led by first author Oliver G. Frost from Loughborough University alongside corresponding authors Abdelhadi Rebbaa and Amit Sharma, from the Lifespan Research Institute, the authors explore growing concerns about the lack of standardization in how frailty is measured in rodent aging studies, which may limit the development of effective interventions targeting age-related decline. Frailty, a key indicator of deteriorating health in older adults, is increasingly assessed in preclinical models using frailty indexes (FIs). These indexes quantify health deficits, such as reduced mobility, cognitive decline, or physical weakness. However, this perspective highlights that FI methodologies vary significantly across studies, from the selection of parameters to the cut-off thresholds used, resulting in inconsistent outcomes that affects reproducibility and translational value. The authors reviewed 18 rodent studies and found substantial variation in how frailty is defined and measured. Some FIs rely on clinical observations, such as appearance or beahaviour, while others focus on physical performance metrics like grip strength or locomotion. In several cases, applying different FIs to the same group of animals produced contradictory results, underscoring the importance of harmonized protocols. To illustrate these issues, the researchers applied an 8-item FI to mice of different ages and found that even young mice were sometimes scored as frail, depending on the scoring method and reference values. This finding emphasizes the need for consistent baselines and controlled environments, especially when comparing across studies. The authors recommend using each animal as its own baseline in longitudinal studies, a strategy that enhances reliability without adding significant cost. “Sex as a biological variable in FIs is an important consideration, as there is a known difference between male and female frailty onset and progression.” The authors also discuss emerging automated tools, such as video-based open-field testing, which can reduce observer bias and improve reproducibility. In the future, broader health indicators, such as cognition, circadian rhythms, social behavior, and body composition, may further enhance frailty assessments. Overall, this work underscores the urgent need for standardized, transparent, and reproducible methods for evaluating frailty in preclinical aging studies. Improved consistency in frailty scoring will better inform the development of healthspan-extending therapies and enhance the translational relevance of animal models. DOI - https://doi.org/10.18632/aging.206307 Corresponding authors - Abdelhadi Rebbaa - rebbaa@gmail.com, and Amit Sharma - amit.sharma@sens.org Abstract video - https://www.youtube.com/watch?v=eha3XA9LyWA Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206307 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, frailty, rodents, frailty index, phenotype To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us on social media at: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

As life expectancy increases, there is growing interest not only in extending lifespan but also in improving the quality of those additional years. To address the physical and cognitive decline that often accompanies aging, researchers have explored a variety of strategies. Many of these focus on a single biological factor, such as reducing inflammation or stimulating stem cell activity. However, aging is a complex process involving multiple, interconnected changes in the body. Recognizing this, researchers at the University of California, Berkeley proposed a more comprehensive approach: targeting multiple aging-related pathways simultaneously. Their study, titled “Sex-specific longitudinal reversal of aging in old frail mice,” was recently featured on the cover of Aging-US (Volume 17, Issue 9). Full blog - https://aging-us.org/2025/10/new-anti-aging-combo-boosts-lifespan-in-old-male-mice/ Paper DOI - https://doi.org/10.18632/aging.206304 Corresponding author - Irina M. Conboy - irina@generationlab.co Abstract video - https://www.youtube.com/watch?v=bpWxDd7hHhM Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206304 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, lifespan, healthspan, Alk5 inhibitor, oxytocin, sex-specific differences To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — October 1, 2025 — A new #research paper #featured as the #cover of Volume 17, Issue 9 of Aging-US was published on August 21, 2025, titled “Sex-specific longitudinal reversal of aging in old frail mice.” The study, led by first author Cameron Kato and corresponding author and Aging-US Editorial Board Member Irina M. Conboy from the University of California, Berkeley, reports that a combination of oxytocin and an Alk5 inhibitor (OT+A5i) significantly extended both lifespan and healthspan in frail, elderly, male mice. These rejuvenating effects were not seen in female mice, highlighting key biological differences between the sexes in their response to aging therapies. The researchers tested a dual-drug approach targeting two biological pathways that change with age. Oxytocin, a hormone that declines with aging and supports tissue repair, was combined with an Alk5 inhibitor that blocks the TGF-beta pathway. TGF-beta becomes overactive with age and contributes to chronic inflammation and tissue damage. In this study, frail mice at 25 months of age—roughly equivalent to 75 human years—were treated regularly with the OT+A5i combination. Male mice receiving the therapy lived over 70% longer than untreated controls and showed significant improvements in physical endurance, agility, and memory. According to hazard ratio analysis, the treated males were nearly three times less likely to die at any given time than untreated males. “Treatment of old frail male mice with OT+A5i resulted in a remarkable 73% life extension from that time, and a 14% increase in the overall median lifespan.” The therapy also reduced “biological noise” in circulating blood proteins—an established marker of aging—bringing those levels back to a more youthful state. Short-term benefits, were seen in both sexes, however, after four months of continuous treatment, only the male mice showed sustained improvement in systemic protein balance. Female mice did not experience significant gains in lifespan or healthspan, though middle-aged females did show improved fertility after treatment. These results underscore the importance of understanding sex-specific biology when developing treatments for aging. While the reasons for these differences remain unclear, the findings provide a new model for studying and designing longevity therapies. Oxytocin is already FDA-approved, and Alk5 inhibitors are currently in clinical trials, suggesting that this approach could be translated to humans. With strong results in aged and frail male animals, OT+A5i appears to be a promising candidate for improving late-life health and survival. DOI - https://doi.org/10.18632/aging.206304 Corresponding author - Irina M. Conboy - irina@generationlab.co Abstract video - https://www.youtube.com/watch?v=bpWxDd7hHhM Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206304 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, lifespan, healthspan, Alk5 inhibitor, oxytocin, sex-specific differences To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

In this episode of the Longevity & Aging Series, Girish Harinath from AgelessRx joins host Dr. Evgeniy Galimov to discuss a research paper he co-authored in Volume 17, Issue 4 of Aging-US, titled “Influence of rapamycin on safety and healthspan metrics after one year: PEARL trial results.” DOI - https://doi.org/10.18632/aging.206235 Corresponding author - Stefanie L. Morgan - stefanie@agelessrx.com Video interview - https://www.youtube.com/watch?v=7-NvskI8Ve0 Longevity & Aging Series - https://www.aging-us.com/longevity Abstract Design: This 48-week decentralized, double-blinded, randomized, placebo-controlled trial (NCT04488601) evaluated the long-term safety of intermittent low-dose rapamycin in a healthy, normative-aging human cohort. Participants received placebo, 5 mg or 10 mg compounded rapamycin weekly. The primary outcome measure was visceral adiposity (by DXA scan), secondary outcomes were blood biomarkers, and lean tissue and bone mineral content (by DXA scan). Established surveys were utilized to evaluate health and well-being. Safety was assessed through adverse events and blood biomarker monitoring. Results: Adverse and serious adverse events were similar across all groups. Visceral adiposity did not change significantly (ηp2 = 0.001, p = 0.942), and changes in blood biomarkers remained within normal ranges. Lean tissue mass (ηp2 = 0.202, p = 0.013) and self-reported pain (ηp2 = 0.168, p = 0.015) improved significantly for women using 10 mg rapamycin. Self-reported emotional well-being (ηp2 = 0.108, p = 0.023) and general health (ηp2 = 0.166, p = 0.004) also improved for those using 5 mg rapamycin. No other significant effects were observed. Conclusions: Low-dose, intermittent rapamycin administration over 48 weeks is relatively safe in healthy, normative-aging adults, and was associated with significant improvements in lean tissue mass and pain in women. Future work will evaluate benefits of a broader range of rapamycin doses on healthspan metrics for longevity, and will aim to more comprehensively establish efficacy. Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206235 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, rapamycin, geroscience, longevity, healthspan To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us on social media at: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

Colorectal cancer is one of the most common—and deadliest—cancers worldwide. Once it spreads and reaches the metastatic stage, treatment becomes far more difficult. Tumors can also behave very differently from one patient to another, especially after multiple rounds of therapy. Precision oncology is helping to overcome these challenges by enabling clinicians to analyze each tumor's unique genetic profile and tailor treatment accordingly. This approach was recently highlighted in a case study published in Volume 16 of Oncotarget. The report detailed how a 62-year-old man with advanced colorectal cancer received a highly personalized treatment plan, developed by an international panel of experts, after completing all standard treatment options. Full blog - https://www.oncotarget.org/2025/09/24/precision-oncology-in-metastatic-colorectal-cancer-a-real-world-case-study/ Paper DOI - https://doi.org/10.18632/oncotarget.28744 Correspondence to - Shai Magidi - shai.magidi@winconsortium.org Abstract video - https://www.youtube.com/watch?v=uWDtWNgpK7A Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28744 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, precision oncology, molecular tumor board, colorectal carcinoma, cancer management To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY - September 24, 2025 – A new #research paper was #published in Volume 16 of Oncotarget on September 22, 2025, titled “Loss of Trp53 results in a hypoactive T cell phenotype accompanied by reduced pro-inflammatory signaling in a syngeneic orthotopic mouse model of ovarian high-grade serous carcinoma.” In this study, led by first author Jacob Haagsma and corresponding author Trevor G. Shepherd from the Verspeeten Family Cancer Centre and Western University, Canada, researchers investigated how the loss of Trp53 – a critical tumor suppressor gene – affects immune responses in ovarian cancer. The team found that deleting Trp53 led to more aggressive tumor growth and a weaker immune response. These findings help explain why some ovarian tumors may be resistant to immunotherapy and point to new ways to improve treatment. High-grade serous ovarian carcinoma (HGSC) is a deadly cancer that is often diagnosed at a late stage. Immunotherapy, which enhances the body's immune system to fight cancer, has shown limited effectiveness in treating this type of cancer. To better understand why, the researchers developed a mouse model that closely mimics human HGSC. They injected ovarian epithelial cells, with and without Trp53, into the fallopian tubes, the origin site of most ovarian cancers. “In this study, we developed a syngeneic model reflecting both the site of origin and the genotype of early HGSC disease by deleting Trp53 in mouse oviductal epithelial (OVE) cells.” Mice injected with cells lacking Trp53 developed faster-growing and more invasive tumors, reflecting how the disease typically progresses in humans. These tumors also had fewer active T cells, which are immune cells responsible for attacking cancer. Moreover, the T cells that were present appeared less capable of responding to the tumor, creating an immune environment that allowed cancer to grow uncontrolled. Further analysis revealed that tumor cells without Trp53 had reduced activity in genes related to inflammation. These changes were associated with lower levels of key proteins that normally help immune cells detect and attack tumor cells. When the researchers collected tumor cells from the abdominal fluid of the mice—a condition that simulates advanced-stage disease—they observed even lower immune signaling than before. This suggests that as the tumor spreads, it becomes better at evading the immune system. This study highlights how early genetic mutations can shape the interaction between tumors and the immune system. In particular, the loss of Trp53 appears to trigger a chain of events that weakens immune surveillance and accelerates tumor progression. These findings emphasize the need to consider both genetic mutations and the tumor environment when designing immunotherapies for ovarian cancer. Understanding how genes like Trp53 influence immune behavior may lead to more effective treatments and help identify which patients are most likely to benefit from immunotherapy. DOI - https://doi.org/10.18632/oncotarget.28768 Correspondence to - Trevor G. Shepherd - tshephe6@uwo.ca Abstract video - https://www.youtube.com/watch?v=WFQw0psuC3M Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28768 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — September 23, 2025 — A new #research paper was #published in Volume 17, Issue 8 of Aging-US on August 7, 2025, titled “Senescent cell heterogeneity and responses to senolytic treatment are related to cell cycle status during senescence induction.” This study, led by first authors Francesco Neri and Shuyuan Zheng, together with corresponding authors Denis Wirtz, Pei-Hsun Wu, and Birgit Schilling from the Buck Institute for Research on Aging, the USC Leonard Davis School of Gerontology, and Johns Hopkins University, reveals that not all aging cells behave the same. The researchers identified key differences between senescent cell subtypes that may influence how well they respond to senolytic drugs. These findings could help guide the development of more effective therapies for age-related diseases. Senescent cells are aged or damaged cells that stop dividing and accumulate in tissues over time. While they play a role in wound healing and protecting against cancer early in life, they can drive chronic inflammation and tissue decline with age. Researchers are exploring ways to selectively remove these cells using senolytic drugs. However, the large variety of senescent cell types has made it difficult to design treatments that work for all of them. This study aimed to better understand the functional differences among senescent cell subpopulations. Using high-resolution imaging, the team analyzed thousands of human endothelial and fibroblast cells growing in the lab. They observed that cells that exited the cell cycle (stopped dividing) in a later phase showed stronger signs of senescence and were more sensitive to senolytic treatment. These cells also produced more IL-6, a molecule associated with inflammation. The findings suggest that DNA content, which varies depending on the cell cycle phase, plays an important role in how aging cells function and how they respond to drugs. “We found that G2-arrested senescent cells feature higher senescence marker expression than G1-arrested senescent cells.” This is the first clear evidence that senescent cells do not all respond equally to treatment. The results suggest that future senolytic therapies could be more successful if they are designed to target specific subtypes of senescent cells, especially those with greater inflammatory potential. While this research was conducted in laboratory cell cultures, it provides a foundation for studying how these findings apply to living tissues. Future work will examine whether similar patterns occur in the body and how this knowledge could lead to more precise and effective treatments for age-related conditions. Understanding the diversity of aging cells is key to developing therapies that are both safer and more targeted. DOI - https://doi.org/10.18632/aging.206299 Corresponding authors - Denis Wirtz — wirtz@jhu.edu, Pei-Hsun Wu — pwu@jhu.edu, and Birgit Schilling — bschilling@buckinstitute.org Abstract video - https://www.youtube.com/watch?v=x8bhKEFLzqA Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206299 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, cellular senescence, imaging, heterogeneity, senolytics, cell cycle To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us on social media at: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — September 16, 2025 — A new #research paper was #published in Volume 17, Issue 8 of Aging-US on August 6, 2025, titled “Age-related trends in amyloid positivity in Parkinson's disease without dementia.” In this study, led by first author Keiko Hatano and corresponding author Masashi Kameyama from the Tokyo Metropolitan Institute for Geriatrics and Gerontology in Japan, researchers found that patients with Parkinson's disease (PD) diagnosed in their 80s showed a significantly higher rate of amyloid positivity—an indicator associated with Alzheimer's disease—compared to those diagnosed at a younger age. Importantly, none of the participants had dementia. These findings suggest that older patients with PD may face a greater risk of future cognitive decline and could benefit from early screening for Alzheimer's-related brain changes. Amyloid-beta is considered a key marker of cognitive decline. While it is known that amyloid accumulation contributes to PD with dementia, its role in patients who have not developed cognitive problems remains less understood. This study aimed to explore how age influences amyloid buildup in people with PD who do not yet show signs of dementia. The researchers analyzed data from 89 individuals with PD and no signs of dementia. Participants were divided into two age-based groups: those diagnosed before age 73 (LOW group) and those diagnosed at age 73 or older (HIGH group). Using cerebrospinal fluid samples, they measured levels of amyloid-beta, a standard method for detecting early Alzheimer's-related changes. The findings revealed that 30.6% of the older group tested positive for amyloid, compared to just 10.0% in the younger group. “[…] we elucidated the prevalence of amyloid positivity in patients with PD without dementia, whose mean age at diagnosis was 80.2 years, using CSF Aβ42 levels.” Interestingly, both age groups of Parkinson's patients had a lower rate of amyloid positivity than cognitively normal individuals of the same age in the general population. This unexpected result suggests that PD may alter how amyloid accumulates in the brain, possibly shortening the phase in which amyloid builds up silently before symptoms appear. The authors suggest that amyloid buildup could accelerate the transition from healthy cognition to dementia in patients with PD. The study also observed age-related associations with other biological markers of Alzheimer's disease, such as tau protein levels. As the global population continues to age and the number of older adults diagnosed with PD grows, identifying early warning signs of cognitive decline becomes increasingly important. These findings may help inform future screening approaches and support the development of therapies aimed at delaying or preventing dementia in people with Parkinson's disease. DOI - https://doi.org/10.18632/aging.206297 Corresponding author - Masashi Kameyama - kame-tky@umin.ac.jp Abstract video - https://www.youtube.com/watch?v=AP8S9evzCJw Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206297 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, amyloid positivity, Parkinson's disease without dementia, cerebrospinal fluid Aβ42 To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us on social media at: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

Idiopathic Pulmonary Fibrosis (IPF) is a progressive lung disease that primarily affects people over the age of 60. It causes scarring in the lung tissue, which gradually reduces lung capacity and makes breathing difficult. Despite years of research, the exact causes of IPF remain largely unknown, and current treatments mainly aim to slow its progression rather than reverse or cure the disease. Because IPF tends to develop later in life, researchers have long suspected a connection with biological aging. This is the focus of a recent study by scientists from Insilico Medicine. Their research, titled “AI-driven toolset for IPF and aging research associates lung fibrosis with accelerated aging,” was published recently in Aging-US, Volume 17, Issue 8. Full blog - https://aging-us.org/2025/09/ai-tools-reveal-how-ipf-and-aging-are-connected/ Paper DOI - https://doi.org/10.18632/aging.206295 Corresponding author - Alex Zhavoronkov - alex@insilico.com Abstract video - https://www.youtube.com/watch?v=24lX2lHbt7o Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206295 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, IPF, generative AI, transformer, proteomics To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us on social media at: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

Immunotherapy is not usually effective against pancreatic cancer (PC), but a new study published in Oncotarget (Volume 16, 2025) highlights rare cases where it did help. These examples, though uncommon, may offer valuable insights for future treatment. Pancreatic Cancer and Immunotherapy Pancreatic cancer is often diagnosed at an advanced stage, which limits treatment options and contributes to its poor prognosis. While chemotherapy remains the standard treatment, it usually offers only modest benefits in terms of survival. Immunotherapy—an approach that activates the immune system to fight cancer—has been effective in other cancers but has shown limited success in PC. This is largely due to the tumor's ability to suppress immune responses and create an environment that protects it from attack. Currently, these drugs are only approved for a small subset of patients whose tumors have a specific genetic feature called high microsatellite instability (MSI-high), found in just 1 to 2 percent of cases. The Study: Pancreatic Cancer Immunotherapy Responders The study, titled “Exceptional responders to immunotherapy in pancreatic cancer: A multi-institutional case series of a rare occurrence,” was led by first author Kavin Sugumar and corresponding author Jordan M. Winter, from University Hospitals Seidman Cancer Center. The researchers examined medical records from 14 patients with pancreatic ductal adenocarcinoma (PDAC) who had responded unexpectedly well to immune checkpoint inhibitors—drugs that help reactivate immune cells to attack cancer. The drugs included PD-1 inhibitors such as pembrolizumab and nivolumab, CTLA-4 inhibitors like ipilimumab, and agents targeting tumor-associated macrophages. To find these rare cases, the research team contacted 471 oncologists from 91 major U.S. cancer centers between 2020 and 2021. Full blog - https://www.oncotarget.org/2025/09/11/immunotherapy-response-in-pancreatic-cancer-what-a-new-study-reveals/ Paper DOI - https://doi.org/10.18632/oncotarget.28739 Correspondence to - Jordan M. Winter - jordan.winter@UHHospitals.org Abstract video - https://www.youtube.com/watch?v=VeWTcuVmqgM Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28739 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, pancreatic adenocarcinoma, immunotherapy, exceptional responders, microsatellite instability, survival To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — September 11, 2025 — A new #research paper was #published in Volume 17, Issue 8 of Aging-US on August 8, 2025, titled “AI-driven toolset for IPF and aging research associates lung fibrosis with accelerated aging.” In this study, researchers Fedor Galkin, Shan Chen, Alex Aliper, Alex Zhavoronkov, and Feng Ren from Insilico Medicine used artificial intelligence (AI) to investigate the similarities between idiopathic pulmonary fibrosis (IPF), a severe lung disease, and the aging process. Their findings show that IPF is not simply accelerated aging, but a distinct biological condition shaped by age-related dysfunction. This insight may lead to a new approach in how scientists and clinicians treat this complex disease. IPF mainly affects individuals over the age of 60. It causes scarring of lung tissue, making it harder to breathe and often leading to respiratory failure. Current treatments can slow the disease but rarely stop or reverse its progression. The researchers used AI to identify shared biological features between aging and fibrosis, finding new potential targets for therapy. The team developed a “proteomic aging clock” based on protein data from more than 55,000 participants in the UK Biobank. This AI-driven tool accurately measured biological age and found that patients with severe COVID-19, who are at increased risk for lung fibrosis, also showed signs of accelerated aging. This suggests that fibrosis leaves a detectable biological trace, supporting the use of aging clocks in studying age-related diseases. “For aging clock training, we used the UK Biobank collection of 55319 proteomic Olink NPX profiles annotated with age and gender.” They also developed a custom AI model, ipf-P3GPT, to compare gene activity in aging lungs versus those with IPF. Although some genes were active in both, many showed opposite behavior. In fact, more than half of the shared genes had inverse effects. This means IPF does not just speed up aging but also disrupts the body's normal aging pathways. The study identified unique molecular signatures that distinguish IPF from normal aging. While both involve inflammation and tissue remodeling, IPF drives more damaging changes to lung structure and repair systems. This difference could guide the development of drugs that specifically target fibrosis without affecting normal aging. By combining AI with large-scale biological data, the study also introduces a powerful toolset for examining other age-related conditions such as liver and kidney fibrosis. These models may support personalized treatments and expand understanding of the relationships between aging and disease, opening new directions for therapy development. DOI - https://doi.org/10.18632/aging.206295 Corresponding author - Alex Zhavoronkov - alex@insilico.com Abstract video - https://www.youtube.com/watch?v=24lX2lHbt7o Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206295 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, IPF, generative AI, transformer, proteomics To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us on social media at: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

As the global population grows older, understanding what drives the aging process is becoming increasingly important. Diseases like Alzheimer's, cardiovascular conditions, and cancer are more common with age, yet many current treatments only manage symptoms rather than addressing the underlying biological causes. One contributor to aging is the buildup of “senescent” cells—cells that have stopped dividing but do not die. These cells can harm nearby tissues by releasing molecular signals, a process known as secondary senescence. Scientists have found that senescent cells release tiny particles called exosomes. A research team from The Buck Institute for Research on Aging recently discovered that these exosomes carry aging-related messages through the bloodstream. Their study, titled “Exosomes released from senescent cells and circulatory exosomes isolated from human plasma reveal aging-associated proteomic and lipid signatures,” was featured as the cover article in Aging (Aging-US), Volume 17, Issue 8. Full blog - https://aging-us.org/2025/09/how-exosomes-spread-aging-signals-and-could-support-anti-aging-research/ Paper DOI - https://doi.org/10.18632/aging.206292 Corresponding author - Birgit Schilling - bschilling@buckinstitute.org Video short - https://www.youtube.com/watch?v=tcyAZahw-g8 Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206292 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, proteomics, senescence, exosomes, data-independent acquisitions To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

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 Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28730 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ 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). To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh MEDIA@IMPACTJOURNALS.COM

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. Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28758 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ 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. Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science). To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh MEDIA@IMPACTJOURNALS.COM

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 Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28762 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, macroautophagy, flux; ER stress, aramchol, regorafenib To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY - August 13, 2025 – A new #research paper was #published in Volume 16 of Oncotarget on July 29, 2025, titled “PCAIs stimulate MAPK, PI3K/AKT pathways and ROS-Mediated apoptosis in aromatase inhibitor-resistant breast cancer cells while disrupting actin filaments and focal adhesion.” In this study, led by first author Jassy Mary S. Lazarte and corresponding author Nazarius S. Lamango from Florida A&M University College of Pharmacy and Pharmaceutical Sciences, researchers investigated a new class of compounds called polyisoprenylated cysteinyl amide inhibitors (PCAIs) as a potential treatment for aromatase inhibitor (AI) therapy resistant breast cancer. Aromatase inhibitors are a common treatment for estrogen receptor-positive (ER+) breast cancer, but many patients eventually develop resistance, leaving fewer therapeutic options. The study focused on a PCAI compound called NSL-YHJ-2-27, which was tested in long-term letrozole-treated breast cancer cells (LTLT-Ca), an experimental model of AI therapy resistance. NSL-YHJ-2-27 activated two major signaling pathways, MAPK and PI3K/AKT. Although these pathways typically support cancer cell survival, their overstimulation by PCAIs led to increased oxidative stress, damaging the cells and inducing cell death by apoptosis. The compound also reduced levels of RAC1 and CDC42, proteins involved in maintaining cell shape and movement. These alterations resulted in cytoskeletal disruption and reduced structural integrity, making the cancer cells more vulnerable and less capable of spreading. Importantly, the effects of NSL-YHJ-2-27 persisted after the compound was removed, suggesting long-term control over AI resistant cancer cells may be possible. “PCAIs inhibited cell proliferation and colony formation by 95% and 74%, respectively, increased active caspase 7 and BAX 1.5-fold and 56%, respectively. NSL-YHJ-2-27 (10 μM) induced LTLT-Ca spheroid degeneration by 61%.” As a new class of targeted molecules, PCAIs represent an innovative approach distinct from traditional endocrine therapies. Their ability to affect multiple cellular mechanisms simultaneously makes them promising candidates for future drug development. Overall, this study presents a promising new approach for treating AI therapy-resistant breast cancer. By targeting cellular pathways that support survival and mobility, PCAIs like NSL-YHJ-2-27 could provide a novel strategy to manage advanced or resistant forms of the disease. Further research, including in vivo studies and clinical trials, will be essential to confirm these findings and evaluate their therapeutic potential. DOI - https://doi.org/10.18632/oncotarget.28759 Correspondence to - Nazarius S. Lamango - nazarius.lamango@famu.edu Video short - https://www.youtube.com/watch?v=8xQEilloO9Q Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28759 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, PCAIs, ROS, MAPK, PI3K/AKT, LTLT-Ca cells To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY – August 11, 2025 – A new #researchpaper was #published in Volume 16 of Oncotarget on July 25, 2025, titled “Dissecting the functional differences and clinical features of R-spondin family members in metastatic prostate cancer.” In this study, researchers led by first author Aiden Deacon and corresponding author Justin Hwang from the University of Minnesota-Twin Cities investigated a group of genes known as the R-spondin family (RSPO1/2/3/4) in advanced prostate cancer (PC). The RSPO gene family regulates Wnt signaling, a pathway involved in cancer progression. Prostate cancer is the most common cancer among men in the United States and becomes especially dangerous when it spreads beyond the prostate. Most patients are treated with hormone therapies that target the androgen receptor; however, many tumors eventually become resistant. The research team analyzed thousands of tumor samples and found that RSPO2 alterations were more common than changes in other R-spondin genes or even some well-known cancer-related genes like CTNNB1 and APC. RSPO2 amplification occurred in over 20% of metastatic prostate cancer. Patients with these alterations showed signs of more aggressive disease, including higher mutation rates and greater tumor complexity. Using laboratory models, the team discovered that RSPO2 increases cancer cell growth and triggers a biological process called epithelial-mesenchymal transition (EMT). EMT is known to promote tumor spread and resistance to standard treatments. Unlike other genes in the same pathway, RSPO2 also appeared to reduce the activity of androgen receptor genes, suggesting it drives a type of prostate cancer that no longer relies on hormones for growth. “In cell lines, RSPO2 overexpression caused up-regulation of EMT pathways, including EMT-regulatory transcription factors ZEB1, ZEB2, and TWIST1.” Importantly, RSPO2 showed structural differences from other R-spondin proteins, which may allow researchers to design drugs that specifically block its activity. Current therapies targeting the Wnt pathway are limited, and there are no approved drugs that inhibit RSPO2. However, this study highlights RSPO2 as a promising therapeutic target, especially for patients who do not respond to existing hormone-based treatments. This research adds critical knowledge about how aggressive prostate cancers develop and persist despite therapy. The identification of RSPO2 as a key driver of disease progression opens new possibilities for treatment strategies aimed at improving outcomes for patients with advanced prostate cancer. DOI - https://doi.org/10.18632/oncotarget.28758 Correspondence to - Justin Hwang - jhwang@umn.edu Video short - https://www.youtube.com/watch?v=iyu5D_c1dbY Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28758 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, RSPO2, prostate cancer, Wnt signaling, genomics, therapeutics To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh MEDIA@IMPACTJOURNALS.COM

Lung cancer, particularly non-small cell lung cancer (NSCLC), is the deadliest cancer worldwide. Cigarette smoking is one of the main causes, but not every smoker develops the disease. This suggests that other biological factors help determine who develops cancer. Researchers from the Division of Pulmonary, Critical Care, Sleep and Occupational Medicine, Indianapolis, and from the Richard L. Roudebush Veterans Affairs Medical Center have now found that cigarette smoke, combined with a weakened DNA repair system, can trigger the early stages of lung cancer, particularly NSCLC. This work, led by first author Nawar Al Nasralla and corresponding author Catherine R. Sears, was recently published in Volume 16 of Oncotarget. Full blog - https://www.oncotarget.org/2025/08/11/cigarette-smoke-and-weak-dna-repair-a-double-hit-behind-lung-cancer-risk/ Paper DOI - https://doi.org/10.18632/oncotarget.28724 Correspondence to - Catherine R. Sears - crufatto@iu.edu Video short - https://www.youtube.com/watch?v=UEiCz834a8c Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28724 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, DNA repair, DNA damage, lung adenocarcinoma, squamous cell carcinoma, Xeroderma Pigmentosum Group C (XPC) To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh MEDIA@IMPACTJOURNALS.COM

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 Video short - https://www.youtube.com/watch?v=awiRhDfiMTE Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28757 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, solid tumors, comprehensive genomic profiling, matched therapy, gene fusions, limit of detection To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh MEDIA@IMPACTJOURNALS.COM

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 Video short - https://www.youtube.com/watch?v=fiJWZ_fKxgs Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28722 Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/ Keywords - cancer, PCNA, androgen receptor, PCNA inhibitors, AR splicing variants, CRPC To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us: Facebook - https://www.facebook.com/Oncotarget/ X - https://twitter.com/oncotarget Instagram - https://www.instagram.com/oncotargetjrnl/ YouTube - https://www.youtube.com/@OncotargetJournal LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh MEDIA@IMPACTJOURNALS.COM