12 songs thank you for listening i appreciate u ♥
new project every month, this is for june. art by @hexxless

not for long [nova chance]

why you talk to me like that [justbainz]

rough to say the least [elevated + seanp]

BUFFALO, NY - July 7, 2025 – A new #research paper was #published in Volume 16 of Oncotarget on June 17, 2025, titled “Genetic characteristics of blastic plasmacytoid dendritic cell neoplasm: A single institution experience.”

In this study, a research team led by first author Fei Fei and corresponding author Michelle Afkhami from the City of Hope Comprehensive Cancer Center investigated a rare and aggressive type of blood cancer called blastic plasmacytoid dendritic cell neoplasm (BPDCN). Their research uncovered frequent mutations in key genes and identified CCDC50 as a potential biomarker for diagnosis and disease monitoring. These findings could help improve how this cancer is detected and treated in the future.

BPDCN most often affects older adults and is known for its rapid progression and poor survival rates. The researchers performed genetic sequencing on 21 patients to better understand the disease. They found that two genes, TET2 and ASXL1, were frequently mutated in these patients and were linked to worse survival, especially in those over 65 years old.

“Our study revealed that TET2 (57%) and ASXL1 (33%) were the most frequently mutated genes, followed by NRAS (29%), SRSF2 (14%), ZRSR2 (14%), and KMT2D (14%).”

The study also discovered that a gene called CCDC50 was expressed at much higher levels in BPDCN samples compared to other blood cancers, such as acute myeloid leukemia and chronic monomyelocytic leukemia. This suggests that CCDC50 may help clinicians distinguish BPDCN from other similar diseases. Importantly, CCDC50 levels dropped significantly in patients whose disease went into remission, highlighting its potential as a tool for tracking disease activity over time.

Researchers further observed that patients who received stem cell transplants lived longer than those who did not, reinforcing the importance of this treatment approach. However, BPDCN remains a challenging disease with an overall poor outlook, making these findings an important step toward better care.

This research provides new insights into the genetic changes behind BPDCN and points to CCDC50 as a promising marker to improve diagnosis and monitor treatment success. Larger studies will be needed to confirm these results and bring these discoveries closer to use in routine medical practice.

DOI - https://doi.org/10.18632/oncotarget.28742

Correspondence to - Michelle Afkhami - mafkhami@coh.org

Video short - 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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Oncotarget

Key Genetic Alterations and Biomarker for Blastic Plasmacytoid Dendritic Cell Neoplasm

A new study published recently as the cover of Aging Volume 17, Issue 6, describes a new method to estimate how fast the brain is aging. By analyzing lipids, or fat molecules, in brain tissue, researchers from the National University of Singapore and Hanze University of Applied Sciences created a biological “clock” called DoliClock. This innovation highlights how conditions such as autism, schizophrenia, and Down syndrome are associated with accelerated brain aging.

Understanding Brain Aging

As people grow older, their brains naturally change. However, in many neurological disorders, these changes seem to appear earlier and progress more rapidly. Disorders like autism, schizophrenia, and Down syndrome reduce quality of life and contribute to premature death. Scientists have long searched for better ways to measure biological age in the brain to understand these processes and develop strategies to slow them down.

Most existing methods for estimating biological age rely on genetic markers, such as DNA methylation, which are chemical modifications of DNA. While useful, these approaches may not fully capture the complexity of aging, especially in the brain. Lipids, which are essential components of brain cells and play important roles in energy storage and signaling, offer another perspective.

Full blog - https://aging-us.org/2025/07/doliclock-a-lipid-based-clock-for-measuring-brain-aging/

Paper DOI - https://doi.org/10.18632/aging.206266

Corresponding author - Brian K. Kennedy - bkennedy@nus.edu.sg

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Keywords - aging, aging clock, down syndrome, autism, schizophrenia, dolichol

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Aging (Aging-US)

DoliClock: A Lipid-Based Clock for Measuring Brain Aging

BUFFALO, NY — July 8, 2025 — A new #research paper was #published in Aging (Aging-US) Volume 17, Issue 6, on May 30, 2025, titled “Impact of waist-to-hip and waist-to-height ratios on physical performance: insights from the Longevity Check-up 8+ project.”

In this study, researchers led by first author Anna Maria Martone and corresponding author Elena Levati from the Fondazione Policlinico Universitario “Agostino Gemelli” IRCCS and Università Cattolica del Sacro Cuore found that adults with higher waist-to-hip and waist-to-height ratios tend to have poorer physical performance. These simple body shape measures emerged as important tools for assessing strength and mobility, which are essential for maintaining independence as people age.

The analysis included data from more than 10,000 Italian adults aged 18 to 98 years who participated in the Longevity Check-up 8+ project, a nationwide health initiative aimed at promoting healthy lifestyles and raising awareness of cardiovascular risks. Researchers measured participants’ waist-to-hip (WHR) and waist-to-height (WHtR) ratios and assessed their physical function using the five-repetition chair stand test, a standard evaluation of lower body strength and mobility.

“Among 10690 participants (mean age 57.0 ± 14.8 y; 54% females), men exhibited higher WHR and WHtR and a higher prevalence of abnormal values (61% and 71%).”

The results showed that individuals with higher waist-to-hip and waist-to-height ratios took longer to complete the test, reflecting reduced physical function. Even after adjusting for lifestyle factors such as diet, exercise habits, and cardiovascular health, these ratios remained strongly linked to poorer performance. The waist-to-height ratio, in particular, proved to be a more effective predictor of physical ability across different age and gender groups.

These findings highlight how abdominal fat, already tied to serious health risks like heart disease and diabetes, may also impair mobility and independence as people age. Monitoring waist measurements could help identify individuals at risk of functional decline, offering a simple tool to support public health in aging populations.

The waist-to-height ratio is especially valuable because of its simplicity and practicality. Requiring only waist and height measurements, it can be easily used in clinical settings and community health programs to screen for potential mobility issues. Encouraging healthy waist sizes through balanced diets and regular exercise could help preserve physical performance and delay age-related decline. These findings may guide future prevention strategies. By identifying individuals at higher risk, healthcare professionals can implement targeted interventions to support long-term health and independence.

DOI - https://doi.org/10.18632/aging.206260

Corresponding author - Elena Levati - elena.levati01@icatt.it

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Keywords - aging, physical performance, body composition, waist-to-hip ratio, waist-to-height ratio, chair-stand test

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Abdominal Fat Linked to Reduced Strength and Mobility in Adults

BUFFALO, NY — July 8, 2025 — As populations worldwide continue to age, understanding the mechanisms and manifestations of cognitive aging is increasingly urgent for science, medicine, and society. Age-related cognitive decline ranges from mild memory lapses to the onset of dementia, and is shaped by a complex interplay of molecular, cellular, systemic, and social determinants.

In this special collection, Aging (Aging-US) seeks to bring together cutting-edge research that spans the cellular and molecular underpinnings of cognitive aging with insights into the psychosocial, behavioral, and environmental factors that modulate its course. By integrating basic biology with translational and societal dimensions, this collection aims to foster a holistic understanding of how and why cognitive function changes with age—and what can be done to preserve it.

We welcome original research articles, reviews, and perspectives across model systems and human studies, particularly those that promote interdisciplinary insights and translational potential.

POTENTIAL TOPICS

Molecular and Cellular Mechanisms

-Senescence, inflammation, and neurodegeneration in cognitive decline
-Mitochondrial dysfunction and oxidative stress in aging neurons
-Neurovascular aging and blood-brain barrier integrity
-Single-cell and spatial transcriptomics of the aging brain
-mTOR, autophagy, and proteostasis in age-related cognitive impairment
-The role of glial cells (microglia, astrocytes) in brain aging

 Genetics and Biomarkers

-Genetic risk factors and epigenetic modifications associated with cognitive aging
-Biomarkers of cognitive resilience and vulnerability
-Neuroimaging and fluid-based biomarkers in aging populations

Interventions and Lifestyle Factors

-Cognitive benefits of caloric restriction, exercise, or senolytic therapies
-Preclinical and clinical trials targeting aging pathways to prevent cognitive decline
-Impact of sleep, nutrition, and metabolic health on cognition in older adults
-Use of cognitive strategies and compensatory techniques to maintain or enhance function in aging

Environmental and Social Contexts

-Impact of social isolation, education, and socioeconomic status on cognitive trajectories
-Lifelong cognitive reserve and its determinants
-Cross-cultural and demographic studies on aging and cognition
-Digital health tools for monitoring or enhancing cognitive function in the elderly

SUBMISSION DETAILS:

-Submission Deadline: March 31, 2026
-Manuscript Format: Please follow the journal’s submission guidelines
-Peer Review: All submissions will undergo a rigorous peer-review process
-Submission Link: https://aging.msubmit.net/cgi-bin/main.plex

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Now Accepting Submissions: Special Collection on Cognitive Aging

Treading Angels

BUFFALO, NY – July 9, 2025 – A new #review was #published in Volume 16 of Oncotarget on June 25, 2025, titled “Challenges and resistance mechanisms to EGFR targeted therapies in head and neck cancers and breast cancer: Insights into RTK dependent and independent mechanisms.”

Researchers from the University of Cincinnati and Cincinnati Veterans Affairs Medical Center reviewed current research on why Epidermal Growth Factor Receptor (EGFR)-targeted therapies often fail in breast and head and neck cancers. The article by Shreya Shyamsunder, Zhixin Lu, Vinita Takiar, and Susan E. Waltz explores how cancer cells evade these treatments by activating alternative survival pathways. This review offers an in-depth look at the molecular barriers to EGFR inhibition and provides insights that could inform the development of more effective and durable treatments.

EGFR is a critical protein that regulates cell growth and survival, and it is frequently overexpressed in breast and head and neck cancers. Although therapies targeting EGFR showed early promise, resistance has become a significant challenge. In breast cancer, resistance mechanisms include the movement of EGFR from the cell surface into the nucleus, where it promotes DNA repair, as well as ligand-dependent activation that helps tumor growth despite therapy. In head and neck cancers, resistance often arises from inflammatory signaling through the TLR4-MyD88 pathway and the loss of tumor suppressor genes like PTEN, which allow cancer cells to bypass EGFR inhibition. The review also describes how tumor cells in both cancers commonly activate other receptor tyrosine kinases (RTKs), such as MET, AXL, and RON, to continue growing even when EGFR is blocked.

By analyzing these resistance mechanisms, the authors highlight combination therapies from current research that target EGFR and other key molecular pathways. Strategies such as dual inhibition of EGFR and MET or blocking inflammation-driven survival signals may enhance treatment outcomes. Several clinical trials are evaluating these approaches in patients. For example, in breast cancer, combinations of EGFR inhibitors with chemotherapy and immune checkpoint inhibitors are being tested to improve responses, particularly in triple-negative breast cancer. In head and neck cancers, trials are investigating EGFR-blocking antibodies like cetuximab combined with immunotherapies such as pembrolizumab and nivolumab. These efforts aim to overcome resistance and provide more effective treatment options for patients with EGFR-driven tumors. The review also emphasizes the necessity of identifying biomarkers to predict which patients are most likely to benefit from EGFR-based therapies.

“A recent phase 1 study has shown that patients with recurrent or metastatic head and neck cancer who received BCA101, a bifunctional dual targeting drug that targets EGFR and TGF-β in combination with pembrolizumab, were able to achieve an overall response rate of 65%.”

This work brings together current knowledge about EGFR resistance and illustrates the difficulties involved in treating breast and head and neck cancers. By mapping the many ways tumors overcome EGFR inhibition, the review highlights opportunities for more tailored and effective treatments in the future.

DOI - https://doi.org/10.18632/oncotarget.28747

Correspondence to - Susan E. Waltz - susan.waltz@uc.edu, and Vinita Takiar - takiarva@ucmail.uc.edu

Video short - https://www.youtube.com/watch?v=RD2W-F3_aX4

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EGFR-Targeted Therapy Resistance in Breast and Head & Neck Cancers

BUFFALO, NY — July 10, 2025 — A new #research paper was #published in Aging (Aging-US) Volume 17, Issue 6, on June 7, 2025, titled “Spermidine supplementation and protein restriction protect from organismal and brain aging independently.”

In this study, led by YongTian Liang and Stephan J. Sigrist from Freie Universität Berlin, Charité Universitätmediz Berlin, and the  Leibniz-German Center for Neurodegenerative Diseases (DZNE), researchers investigated how spermidine, a natural substance in the body, and protein intake levels influence aging in fruit flies. They found that spermidine supplementation and changes in protein intake influenced brain health and aging in distinct ways. These insights could guide the development of new strategies to slow age-related decline in humans.

“In this study, we combined low- and high-protein diets (2% versus 12% yeast in food) with spermidine supplementation in aging Drosophila fruit flies.”

Aging of the brain and body contributes to cognitive decline and diseases in older populations. Scientists have long explored dietary restriction and fasting as ways to slow these processes. This study reveals that spermidine supplementation supports brain health by enhancing mitochondrial function and memory, while protein restriction independently promotes longevity and protects against movement decline.

The researchers discovered that spermidine improved memory and preserved physical activity in aging flies regardless of protein intake. In contrast, reducing protein alone boosted mitochondrial activity and extended lifespan without directly enhancing memory. Importantly, the combined approach of protein restriction and spermidine supplementation provided additive benefits, suggesting potential for synergistic effects.

This work highlights that spermidine acts through a pathway involving hypusination, a vital process where cells modify proteins to support energy production and repair, while protein restriction works via nutrient-sensing pathways that promote longevity. These independent mechanisms may explain why combining the two interventions offers greater protection against aging effects.

Although conducted in flies, the study underscores the possibility of designing dietary and supplement-based interventions to combat human age-related decline. As spermidine levels naturally decline with age, supplementation combined with moderated protein intake could offer a safe way to promote brain health and longevity in humans.

The authors point out that it takes further studies in mammals and humans to validate these results. If confirmed, such strategies could lead the way for accessible approaches to promote healthy aging and reduce the burden of cognitive disorders in older populations.

DOI - https://doi.org/10.18632/aging.206267

Corresponding authors - YongTian Liang - yongtian.tim.liang@gmail.com, and Stephan J. Sigrist - stephan.sigrist@fu-berlin.de

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Keywords - aging, brain aging, spermidine, protein restriction, mitochondria

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Spermidine and Protein Restriction Independently Protect Brain and Body from Aging in Flies

Born Woolfinius Jackson Whürl to two itinerate circus gymnasts, Woolfin would grow tired of the performance life and would go on to seek quieter pastures as a painter and later a writer.

New project every month (o_O)

𝙲𝚛𝚎𝚊𝚝𝚎 + 𝙴𝚟𝚘𝚕𝚟𝚎

believe & u will succeed

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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/

Cancer and aging are two sides of age-related tumorigenesis.

The mission of the journal is to understand the mechanisms surrounding aging and age-related diseases, including cancer as the main cause of death in the modern aged population.

The journal aims to promote 1) treatment of age-related diseases by slowing down aging, 2) validation of anti-aging drugs by treating age-related diseases, and 3) prevention of cancer by inhibiting aging. (Cancer and COVID-19 are age-related diseases.)

Read about the Aging (Aging-US) Scientific Integrity Process: https://aging-us.com/scientific-integrity

New tracks tagged #Journal