BUFFALO, NY - December 30, 2024 – A new #editorial was #published in Oncotarget's Volume 15 on December 24, 2024, titled “Pitfalls and perils from FDA-approved germ-line cancer predisposition tests."

Authored by Dr. Wafik S. El-Deiry, Editor-in-Chief of Oncotarget, and Dr. Eli Y. Adashi from Brown University, the article highlights concerns about the risks of a newly approved genetic test for cancer risk. This test, called the “Invitae Common Hereditary Cancers Panel," was approved in 2023 and examines 48 genes linked to inherited cancers, including breast, ovarian, and Lynch syndrome-related cancers. Although the test increases access to genetic information, the authors warn that using it without professional guidance may lead to confusion, stress, and potential harm.

One concern is that people can order this test online without consulting healthcare professionals or genetic counselors. Without expert help, users might struggle to understand their results especially if they indicate risks that are unclear or difficult to act on. This can cause unnecessary anxiety and confusion.

“The DTC option of germ-line testing for cancer susceptibility should be discouraged given the risks of anxiety, lack of adequate interpretation for variants not strongly associated with cancer, potential for minors to be tested outside the healthcare system and potential for loss of follow-up if test results are not shared with health care professionals or never make it into the medical record.”

The editorial also points out ethical and medical issues when minors use these tests. If a child’s test is done without medical oversight, results might not be added to their health records, making follow-up care harder to manage and potentially risking their long-term health.

Cost is another issue. These tests are often not covered by insurance, which can place a financial burden on families who might need additional testing or medical advice.

The researchers emphasize that genetic testing for cancer risk should always include healthcare providers and genetic counseling. This ensures users fully understand their results and receive proper guidance. The authors also call on the US Food and Drug Administration (FDA) to provide clear rules for using these tests, particularly for minors.

In conclusion, while genetic testing holds great potential for improving cancer prevention and care, its benefits must not come at the cost of safety and public health. Responsible use of these tests will require collaboration between regulators, healthcare professionals, and testing companies to address the risks and ensure these tools are used effectively.

DOI - https://doi.org/10.18632/oncotarget.28677

Correspondence to - Wafik S. El-Deiry - wafik@brown.edu

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

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About Oncotarget 

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

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

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Oncotarget

Pitfalls of FDA-Approved Germline Cancer Predisposition Tests

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

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Keywords - cancer, Blastic plasmacytoid dendritic cell neoplasm (BPDCN), Next-generation sequencing (NGS), CCDC50

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Genetic Study Identifies Potential Diagnostic Marker for Rare Blood Cancer BPDCN

In this episode, Ji Li discusses her book, At the Frontier of God’s Empire with Chloë Starr. The book tells the story of French missionary Alfred Caubrière who before his murder in 1948 left behind some 800 letters to his family, as well as 13 volumes of transcripts of everyday conversations in the local dialect among villagers in Santaizi, Manchuria. The episode discusses the life of Caubrière and especially his experience of the weeks-long siege of Santaizi church by the Boxer Rebels in 1900, as well as his depictions of the lives and beliefs of local Catholics.

Ji Li,  At the Frontier of God’s Empire: A Missionary Odyssey in Modern China

BUFFALO, NY — October 23, 2025 — A new #research paper was #published in Volume 17, Issue 9 of Aging-US on September 11, 2025, titled “Roles of plasminogen activator inhibitor-1 in aging-related muscle and bone loss in mice.”

In this study led by first author Takashi Ohira and corresponding author Hiroshi Kaji from Kindai University Faculty of Medicine, researchers found that female mice lacking the gene for plasminogen activator inhibitor-1 (PAI-1) were protected from age-related muscle weakness and bone thinning. This suggests that PAI-1 could be a potential target for future treatments to reduce frailty in aging populations.

As the global population continues to age, more people are affected by conditions such as sarcopenia and osteoporosis. These disorders involve the progressive loss of skeletal muscle mass and bone density, leading to reduced mobility, a greater risk of falls, and a lower quality of life.

To investigate the role of PAI-1 in aging, researchers compared young (6-month-old) and aged (24-month-old) male and female mice, with and without the PAI-1 gene. They found that PAI-1 levels increased with age in both sexes. However, only female mice lacking the PAI-1 gene experienced a significant reduction in age-related muscle and bone loss.

Female mice without PAI-1 maintained stronger grip strength and greater muscle mass in their lower limbs. They also showed less cortical bone loss in their femurs and tibias. In contrast, male mice did not experience the same benefits, despite also showing increased levels of PAI-1 with age. These results suggest that PAI-1 contributes to aging-related decline in a sex-specific manner.

“The present study found that lower limb muscle mass, gastrocnemius and soleus muscle tissue weights, and grip strength were significantly lower in 24-month-old male and female wild-type mice than in their 6-month-old counterparts.”

PAI-1 plays key roles in blood clotting, inflammation, and cellular senescence—a process in which aging cells release harmful molecules that affect nearby tissues. One of these molecules, interleukin-6 (IL-6), is a major driver of inflammation. The researchers found that aged female mice lacking PAI-1 had lower IL-6 levels in both muscle and blood, suggesting that PAI-1 may contribute to muscle and bone loss by promoting inflammation. These protective effects were also not associated with changes in muscle protein turnover or reductions in fibrous tissue, reinforcing the idea that PAI-1’s impact is likely driven by inflammatory signaling.

This study highlights PAI-1 as a promising therapeutic target for slowing or preventing age-related declines in muscle and bone health, particularly in women. Since postmenopausal women are especially vulnerable to osteoporosis and frailty, a better understanding of how PAI-1 contributes to aging could lead to new strategies for maintaining strength and mobility in later life. Further research is needed to explore how PAI-1 interacts with other age-related biological changes and why its effects differ between sexes.

DOI - https://doi.org/10.18632/aging.206318

Corresponding author - Hiroshi Kaji - hkaji@med.kindai.ac.jp

Abstract video - https://www.youtube.com/watch?v=hg4qKf-oO2I

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Aging-US

PAI-1 Deficiency Protects Aging Female Mice from Muscle and Bone Loss

In this special episode of the Yale University Press podcast, Jennifer Banks, Senior Executive Editor in Religion and the Humanities, talks with Anthony T. Kronman about his latest book, True Conservatism: Reclaiming Our Humanity in an Arrogant Age.

Jennifer Banks in Conversation with Anthony T. Kronman

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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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

Lauren Jackson is a religion columnist for the New York Times where she is the associate editor and writer for The Morning, the Times's flagship daily newsletter. Over the past year, she has been deeply involved in reporting on belief. Lauren developed 'Believing,' a project that explores how we experience religion and spirituality in contemporary times. Lauren's thought-provoking columns delve into the complexities of faith, spirituality, and society. In this episode of The Leader’s Way, Lauren discusses the powerful transformation that is possible when we turn our attention to the people around us, attending to hyper-local needs, longings, and joys within our own community.

Host: Brandon Nappi
Guest: Lauren Jackson

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69: Believing with Lauren Jackson

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 

 

Instagram: @theleadersway.podcast berkeleydivinity.yale.edu/podcast 

 

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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

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.

Read about the Oncotarget Scientific Integrity Process: https://www.oncotarget.com/scientific_integrity/

Pitfalls of FDA-Approved Germline Cancer Predisposition Tests

Oncotarget Podcast

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