A new editorial paper was published in Oncotarget's Volume 14 on February 11, 2023, entitled, “Unlocking the potential of molecular-driven stratification for osteosarcoma treatment and prognosis.”

Over the last 40 years, the complex genetic landscape, the heterogeneity of the microenvironment and the cell plasticity of Osteosarcoma (OSA) tumors have delayed the therapeutic and prognostic stratification of patients and the introduction of new efficient treatments. 

As a direct consequence, the vast majority of trials still don’t benefit from a selection of OSA patient-based on molecular evidence before drug administration. This lack of stratification leads to difficult interpretation of outcome, especially with targeted agents such as multikinase inhibitors or anti-osteoclastic drugs.

“Meanwhile, fortunately, the accumulation of numerous sparse but converging observations from many research and clinical teams have progressively drawn a portrait of the resistant osteosarcoma that’s paved the way to new translational discoveries.”

In their new editorial, researchers Gaël Moquin-Beaudry, Maria Eugenia Marques da Costa, Nathalie Gaspar, and Antonin Marchais from Université Paris-Saclay discussed their recent study using unsupervised machine learning algorithms to classify OSA at diagnosis based on gene expression modules functionally enriched for immune microenvironment and tumor phenotypic traits.

“Recently, several important studies have described OSA molecularly at an unprecedent[ed] level of detail taking advantage of multiomics approaches and artificial intelligence [1–3].”


Read the full editorial: DOI: https://doi.org/10.18632/oncotarget.28364 

Correspondence to: Antonin Marchais - ANTONIN.MARCHAIS@gustaveroussy.fr 

Keywords: multiomics, osteosarcoma, bone sarcoma,
stratification

About Oncotarget

Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.

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Oncotarget

Unlocking the Potential of Molecular-Driven Stratification of Osteosarcoma

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

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

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

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

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

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

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

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

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

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

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

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Aging-US

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

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

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

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Keywords - aging, alpha-synuclein, transgenic rat model, different brain regions, transcriptome analysis

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Alpha-Synuclein Triggers Early Gene Expression Changes in Parkinson’s Disease Model

What do we do with our pain? It’s an important spiritual question, and one that Brandon Nappi explores with James Kimmel, Jr., JD, on this episode of Within, a contemplative segment of The Leader's Way Podcast, that explores the convergence of mental health, art, and spirituality through authentic conversations across traditions about personal and collective transformation. James Kimmel is a violence researcher, psychiatry professor, and author who explores the science of revenge, addiction, forgiveness, and violence. A breakthrough scholar, James first identified compulsive revenge-seeking as an addiction. He made the study of revenge and forgiveness his life's work after nearly committing a mass shooting as a teenager. 

 

Host: Brandon Nappi 

Guest: James Kimmel 

 

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70: On Revenge with James Kimmel

BUFFALO, NY — November 5, 2025 — A new #research paper was #published in Volume 17, Issue 10 of Aging-US on September 10, 2025, titled “Longitudinal associations of epigenetic aging with cognitive aging in Hispanic/Latino adults from the Hispanic Community Health Study/Study of Latinos.”

In this study led by Myriam Fornage, from The University of Texas Health Science Center at Houston, researchers found that faster biological aging, measured by DNA-based epigenetic clocks, is associated with greater cognitive decline and higher risk of mild cognitive impairment (MCI) in Hispanic/Latino adults. The results highlight the potential of epigenetic clocks to track changes in brain health over time, helping improve early detection and monitoring of age-related cognitive problems.

Cognitive decline and dementia are major public health concerns, especially among aging populations. In this study, researchers followed 2671 Hispanic/Latino adults (average age 57; 66% women) over a seven-year period. They measured each participant’s biological age using epigenetic clocks and assessed their cognitive performance at two time points.

“We evaluated the associations of 5 epigenetic clocks and their between-visit change with multiple measures of cognitive aging that included a global and domain-specific cognitive function score at each visit, between-visit change in global and domain-specific cognitive function score, and MCI diagnosis at visit 2 (V2).”

Epigenetic clocks estimate biological age based on DNA chemical modifications, called methylation, that accumulate with age. The study evaluated five different clocks, including newer models like GrimAge and DunedinPACE, which are designed to more accurately reflect health-related aging.

The researchers found that individuals with faster biological aging showed lower cognitive function and higher probability of developing MCI over time. Among the five clocks studied, newer models such as GrimAge and DunedinPACE showed the strongest associations with memory, processing speed, and overall brain health. These findings suggest that tracking changes in biological age over time may be more effective than relying on a single measurement to identify those at risk for cognitive impairment.

Importantly, the associations between biological aging and cognitive decline remained significant even after accounting for other known risk factors such as education, language preference, and cardiovascular health. This supports the idea that epigenetic clocks capture unique biological processes that influence brain aging. The study also found that the impact of changes in biological age over time was comparable to that of APOE4, a well-established genetic risk factor for Alzheimer’s disease.

Overall, this is the first large-scale study to examine these associations in a Hispanic/Latino population, a group that is underrepresented in aging research. By identifying early biological signs of brain aging, this work highlights the potential of epigenetic clocks as tools for routine health assessments. Monitoring changes in these biological markers could help detect individuals at risk for cognitive decline and guide timely interventions to preserve brain health.

DOI - https://doi.org/10.18632/aging.206317

Corresponding author - Myriam Fornage - Myriam.Fornage@uth.tmc.edu

Abstract video - https://www.youtube.com/watch?v=kG0Y-F_sods

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Epigenetic Aging Linked to Cognitive Decline in Hispanic/Latino Adults

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

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Keywords - cancer, hypoxia, lipid droplets, ferroptosis, resistance, prostate

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How Low Oxygen Shields Prostate Cancer from Ferroptosis Therapies

BUFFALO, NY - November 10, 2025 – A new #research paper was #published in Oncotarget (Volume 16) on November 6, 2025, titled “Anti-DNA virus agent cidofovir - loaded green synthesized cerium oxide nanoparticles (Nanoceria): Nucleic acids (DNA and RNA) binding affinity and cytotoxicity effects.”

In this study, led by Nahid Shahabadi from Razi University in Kermanshah, researchers developed an environmentally friendly approach to enhance the performance of cidofovir, a drug used to treat infections caused by DNA viruses. The work responds to the growing need for therapies that are safer, more effective, and better targeted.

The research team developed a new compound by loading cidofovir onto green-synthesized cerium oxide nanoparticles (nanoceria), known as CDV-CeO2 NPs. This method combines the drug’s antiviral and anticancer properties with the biological activity of nanoceria, which is known for its antioxidant, anti-inflammatory, and tumor-targeting effects. To avoid toxic chemicals, the nanoparticles were synthesized using quince fruit peel extract, making the process more sustainable and suitable for medical applications.

Laboratory experiments showed that the CDV-CeO2 nanoparticles were significantly more effective at killing breast cancer cells than either cidofovir or cerium oxide nanoparticles alone. At the highest tested concentration, the new compound destroyed more than 97% of cancer cells, compared to 72% with cidofovir alone and 50% with nanoparticles alone. These findings suggest that the combined formulation enhances anticancer activity and may allow for lower drug doses with fewer side effects.

To understand how these nanoparticles interact with genetic material, the team studied their binding to DNA and RNA, two key molecules involved in cancer development and viral replication. CDV-CeO2 nanoparticles showed strong binding affinity through two mechanisms: groove binding, which fits into natural curves of the genetic molecule strands, and intercalation, which inserts between base pairs. The nanoparticles formed stable complexes that responded to temperature, indicating reliable interactions in biological systems.

“The novelty of this work lies in the innovative green synthesis method, the dual-functional therapeutic application, and the enhanced biological activity of the CDV-CeO2 NPs, which collectively position these nanoparticles as promising candidates for future cancer and antiviral therapies.”

This research presents a potential new strategy for improving drug targeting and delivery using green nanotechnology. The approach could lead to more effective treatments for diseases such as breast cancer and infections caused by human papillomavirus (HPV) and other DNA viruses. However, further research, including animal and clinical studies, is needed to confirm the safety and long-term effectiveness of this treatment.

Overall, this study represents a significant step toward combining natural materials with nanomedicine to create more efficient therapies. If supported by future research, CDV-CeO2 nanoparticles could offer a new generation of dual-action treatments.

DOI - https://doi.org/10.18632/oncotarget.28774

Correspondence to - Nahid Shahabadi - nahidshahabadi@yahoo.com

Abstract video - https://www.youtube.com/watch?v=Il9CsfgO2mU

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Eco-Friendly Nanoparticles Improve Cidofovir’s Anticancer and Antiviral Effects

BUFFALO, NY — November 11, 2025 — A new #research paper was #published in Volume 17, Issue 10 of Aging-US on October 1, 2025, titled “L-β-aminoisobutyric acid (L-BAIBA) in combination with voluntary wheel running exercise enhances musculoskeletal properties in middle-age male mice.”

In this study led by first author Julian A. Vallejo and corresponding author Michael J. Wacker from the University of Missouri, Kansas City, researchers investigated how L-β-aminoisobutyric acid (L-BAIBA), a natural compound released during exercise, works together with regular physical activity to improve muscle and bone health in middle-aged male mice. The findings may support new strategies to maintain musculoskeletal health in aging populations, especially those at risk for mobility loss or osteoporosis.

Muscle and bone strength naturally decline with age, increasing the risk of falls, fractures, and reduced quality of life. While exercise remains the most effective way to counteract this deterioration, it is often difficult for older individuals to maintain sufficient activity levels to see results. L-BAIBA, a molecule naturally produced during physical activity, is known to promote energy metabolism and support muscle and bone cells. This study explored its potential to work in synergy with endurance exercise to maximize health benefits in aging bodies.

Researchers studied 12-month-old male mice that were split into different groups. Some remained sedentary, while others exercised freely on running wheels. Half of each group received daily L-BAIBA supplementation. After three months, the mice that received both the supplement and exercise showed greater improvements than those receiving either one alone. The soleus, a slow-twitch muscle essential for endurance and balance, grew larger and stronger only in the combined treatment group. These muscles also shifted to a more fatigue-resistant fiber type and had a larger number of oxidative fibers.

“To investigate this hypothesis, we subjected 12-month-old (as a model of middle-age) male C57BL6 mice to voluntary wheel running (VWR) with L-BAIBA (100mg/kg/day) (VWR+L-BAIBA), VWR alone, L-BAIBA alone, or none (CTRL) for three months.”

The study also showed significant improvements in bone health. Mice that received both exercise and L-BAIBA developed thicker and denser trabecular bone, along with reduced fat levels in the bone marrow, indicators of stronger, healthier bones. These changes were not observed in the groups that only exercised or only received L-BAIBA. Although the compound caused minor changes in heart electrical activity, it did not affect heart size or overall function, suggesting it is safe in this setting.

These findings suggest that L-BAIBA may enhance the benefits of physical activity by supporting muscle strength and bone structure, particularly in slow-twitch muscle fibers. This combination could serve as a therapeutic strategy to help older adults, including those unable to engage in regular exercise, maintain musculoskeletal health.

As the aging population grows, there is a growing need for solutions that support muscle and bone health without requiring strenuous activity. This research highlights the potential of natural, exercise-related molecules like L-BAIBA to help maintain mobility and strength throughout aging.

DOI - https://doi.org/10.18632/aging.206325

Corresponding author - Michael J. Wacker — wackerm@umkc.edu

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

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Exercise and L-BAIBA Supplement Boost Muscle and Bone Health in Aging Mice

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

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Keywords - aging, alpha-synuclein, transgenic rat model, different brain regions, transcriptome analysis

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Alpha-Synuclein Overexpression in Rats Reveals Early Clues to Synucleinopathies

We practice meditation because the present moment is the only place where we can truly find ourselves, love others, and be loved by the divine. This is why we gather, why we sit, why we breathe together. We practice surrendering to what lies beyond our control and responding rather than reacting to life's challenges. We cultivate curiosity about what's arising within and around us, learning to do difficult things like changing and growing. Because we trust there's a limitless reservoir of strength, compassion, and resilience flowing through us at every moment. 


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71: "Why We Practice" - reflection and meditation with Brandon Nappi

Aging-US proudly sponsored the Future of Aging Research (FAR) Mixer 2025, hosted by the Aging Initiative on November 7 in Cambridge, MA, uniting students, researchers, and biotechnology leaders to advance aging research and shape a healthier, longer-lived future.

Highlights from the FAR Mixer 2025

The 2025 FAR Mixer featured keynote speaker Dr. Kristen Fortney, Co-Founder and CEO of BioAge Labs, who shared insights into how translational research and clinical pipelines have evolved over the past decade. 

Dr. Fortney highlighted how obesity-targeting drugs are opening new avenues for metabolic and aging research. She explained that while obesity and osteoporosis are currently major therapeutic priorities, the next wave of reimbursable diseases will likely focus on muscle loss and chronic inflammation, reflecting their growing recognition as key factors in healthy aging. 

She also emphasized the importance of human databases in target discovery, cross-sector partnerships between pharma and biotech, and the increasing focus on small-molecule interventions to address age-related diseases.

Focus talks showcased the diversity and depth of modern aging research.

Full recap - https://aging-us.org/2025/11/aging-us-supports-the-future-of-aging-research-mixer-2025/

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Aging-US Supports the Future of Aging Research Mixer 2025

Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form and then quickly released to Pubmed.

Oncotarget is now indexed by MEDLINE, PubMed and PMC/PubMed.

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Unlocking the Potential of Molecular-Driven Stratification of Osteosarcoma

Oncotarget Podcast

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