A new review paper was published in Oncotarget's Volume 14 on February 25, 2023, entitled, “What is hemoglobin, albumin, lymphocyte, platelet (HALP) score? A comprehensive literature review of HALP’s prognostic ability in different cancer types.”

Since its inception, the Hemoglobin, Albumin, Lymphocyte, Platelet (HALP) Score has gained attention as a new prognostic biomarker to predict several clinical outcomes in a multitude of cancers. 

“HALP is a novel immune-nutritional marker that integrates several routinely collected indicators of immune status, such as the platelet and lymphocyte count, nutritional status, such as albumin, and hemoglobin, a marker for anemia.”

In this new review, researchers Christian Mark Farag, Ryan Antar, Sinan Akosman, Matthew Ng, and Michael J. Whalen from George Washington University School of Medicine searched PubMed for articles on HALP, from the first paper in 2015 through September 2022. Their search yielded a total of 32 studies that evaluated HALP's association with various cancers, including Gastric, Colorectal, Bladder, Prostate, Kidney, Esophageal, Pharyngeal, Lung, Breast, Cervical cancers, and others. 

“This review highlights the collective association HALP has with demographic factors such as age and sex in addition to TNM staging, grade, and tumor size.”

Furthermore, this review summarizes HALP's prognostic ability to predict overall survival, progression-free survival and recurrence-free survival, among other outcomes. In some studies, HALP has also been able to predict response to immunotherapy and chemotherapy. Their review article also aims to serve as a comprehensive and encyclopedic report on the literature that has evaluated HALP as a biomarker in various cancers, highlighting the heterogeneity surrounding HALP's utilization. 

“Because HALP requires only a complete blood count and albumin - already routinely collected for cancer patients - HALP shows potential as a cost-effective biomarker to aid clinicians in improving outcomes for immuno-nutritionally deficient patients.”

Full review: DOI: https://doi.org/10.18632/oncotarget.28367 

Correspondence to: Christian Mark Farag - cmfarag@gwu.edu 

Keywords: HALP score, biomarker, prognosis, cancer, survival

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

HALP Score: Prognostic Ability in Cancers - A Literature Review

In this episode, Michelle Snyder, author, therapist, leadership coach, and the executive director of Soul Shop, speaks directly to faith leaders about the importance of talking about and tending to suicide in our communities, and training for the work of suicide prevention. Michelle talks with Brandon, Whitney, and Misty about the moment we are in, in which isolation is growing and suicide is on the rise, but faith communities have something to offer.

*If you or someone you know is experiencing suicidal thoughts or a crisis, please reach out immediately to the National Suicide Prevention Lifeline at 988.

Host: Brandon Nappi with Whitney Coe and Misty Krasawksi
Guest: Michelle Snyder
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62: We Have To Talk About Suicide with Michelle Snyder

BUFFALO, NY — September 9, 2025 — A new #research paper was #published in Volume 17, Issue 8 of Aging-US on August 1, 2025, titled “Causal relationships between gut microbiome and hundreds of age-related traits: evidence of a replicable effect on ApoM protein levels.”

In this study, Federica Grosso, Daniela Zanetti, and Serena Sanna from the Institute for Genetic and Biomedical Research (IRGB) of the National Research Council (CNR), Italy, uncovered new associations between gut microbiome and the aging process. The researchers found that certain microbial characteristics may causally influence proteins in the blood linked to inflammation and heart health. These findings could help explain how age-related diseases like cardiovascular conditions and macular degeneration are influenced by changes in the gut ecosystem.

The gut microbiome, the collection of microorganisms living in the digestive system, plays a major role in immune function and metabolic health. As people age, this microbial community shifts, often leading to imbalances associated with inflammation and chronic disease. To explore how these changes might affect the body, the researchers used Mendelian Randomization—a method that leverages genetic data—to test over 55,000 possible causal connections between gut microbial characteristics and age-related health indicators.

The study identified 91 significant causal relationships. Among them, the researchers found that higher levels of certain gut bacteria were associated with increased risk of age-related macular degeneration. Another finding was the association between a metabolic pathway in the gut, called “purine nucleotides degradation II,” and lower levels of apolipoprotein M (ApoM), a protein that helps protect against heart disease. This result was validated using data from an independent study, strengthening the evidence.

“Unlike previous studies, we performed replication analyses for the significant results using independent GWAS datasets, a fundamental step that has often been overlooked.”

The study also revealed how some bacteria may affect protein levels differently depending on a person’s blood type. Specifically, in individuals with blood type A, certain gut microbes that can break down a sugar called GalNAc may influence proteins related to inflammation and cardiovascular health. This suggests that personalized approaches to managing age-related diseases could consider both gut microbiota and genetic factors like blood type.

The research team followed strict guidelines to reduce false findings and confirmed its key results in independent datasets. By carefully testing for reverse causality and other biases, the authors provided strong evidence that the gut microbiome can influence critical aspects of aging biology.

Although more research is needed to fully understand the biological pathways involved, these findings suggest that targeting the gut microbiota might help delay or reduce age-related inflammation and disease. The study lays a foundation for future therapeutic strategies that could include diet, probiotics, or other microbiome-based interventions.

DOI - https://doi.org/10.18632/aging.206293

Corresponding author - Serena Sanna - serena.sanna@cnr.it

Abstract video - https://www.youtube.com/watch?v=CWky6jlHKUs

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Aging-US

Gut Microbiome Influences Proteins That Drive Aging and Disease

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

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Keywords - aging, IPF, generative AI, transformer, proteomics

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AI Tools Uncover New Link Between Idiopathic Pulmonary Fibrosis and Aging

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

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Keywords - cancer, pancreatic adenocarcinoma, immunotherapy, exceptional responders, microsatellite instability, survival

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Immunotherapy Response in Pancreatic Cancer: What a New Study Reveals

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

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Keywords - aging, IPF, generative AI, transformer, proteomics

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AI Tools Reveal How IPF and Aging Are Connected

Welcome to 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. In this inaugural episode, Brandon talks
with Joanna Penn, an award-winning New York Times and USA Today bestselling author,
whose latest book, “Pilgrimage: Lessons Learned from Solo Walking Three Ancient Ways,”
explores the rich themes of spirituality, mental health, and personal transformation. Tune in for
a conversation about the power of walking, writing, and leaning into the call on our hearts.

Host: Brandon Nappi

Guest: Joanna Penn

Production: Goodchild Media

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Surprised by Pilgrimage with Joanna Penn

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

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Keywords - aging, amyloid positivity, Parkinson's disease without dementia, cerebrospinal fluid Aβ42

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Older Adults with Parkinson’s Disease Have Increased Brain Amyloid Without Dementia

Hannah and Mark interview Jimmy Hatch, a recent Yale graduate and 26-year US military veteran who is the host of the new podcast, The Ivy League Insurgent. As a former Navy SEAL, Purple Heart recipient, and nonprofit founder, Jimmy became Yale’s oldest freshman at the age of 52. In their interview, Jimmy reflects on his remarkable story, the importance of connecting with those who are different, and how the humanities have shaped his understanding of what it means to be a “better human.”  

Interview with Jimmy Hatch ’24, The Ivy League Insurgent

BUFFALO, NY — September 18, 2025 — A new #research paper was #published  in Volume 17, Issue 8 of Aging-US on August 9, 2025, titled “The myokine FGF21 associates with enhanced survival in ALS and mitigates stress-induced cytotoxicity.”

In this study, led by first author Abhishek Guha and corresponding author Peter H. King from the University of Alabama at Birmingham and the Birmingham Veterans Affairs Medical Center, researchers discovered that a hormone called FGF21, which is released by muscles, is elevated in people with amyotrophic lateral sclerosis (ALS) and may play a protective role. These findings are especially relevant because ALS is a fatal and currently incurable neurodegenerative disease.

Amyotrophic lateral sclerosis is an age-related and progressive condition that affects the nerve cells responsible for muscle control. While some treatments can slow the disease, there is still a need to understand why ALS progresses at different rates in different individuals.

“In a prior muscle miRNA sequencing investigation, we identified altered FGF pathways in ALS muscle, leading us to investigate FGF21.”

The research team analyzed muscle biopsies, spinal cord tissue, and blood samples from ALS patients and found that FGF21 levels were significantly elevated. This increase was particularly evident in atrophied muscle fibers—those that had shrunk due to nerve loss—and in the surrounding tissue. Importantly, patients with higher plasma levels of FGF21 showed slower loss of function and longer survival, with some living more than six years after diagnosis.

Using animal models and cultured cells, the researchers demonstrated that FGF21 levels rise even in the early, symptom-free stages of ALS. The hormone appeared to protect both muscle and motor neurons from stress-related damage. When added to stressed cells, FGF21 improved cell survival and reduced markers of cell death. In human muscle cells, FGF21 also supported the formation of new muscle fibers, a process known as myogenesis.

Blood tests revealed that patients with higher levels of FGF21 not only experienced slower disease progression but also tended to have a higher body mass index (BMI), a factor previously associated with longer survival in ALS. This suggests that FGF21 may reflect a patient’s ability to counteract ALS through natural protective mechanisms. It could also serve as a biomarker to monitor disease severity and potentially guide treatment decisions.

The study also investigated how FGF21 communicates with cells. It found that the hormone’s activity depends on a protein called β-Klotho, which was also altered in ALS-affected tissues. These changes were especially noticeable in motor neurons and muscle cells under stress, further highlighting FGF21’s role in the body’s response to damage.

While the study does not show that FGF21 can be used as a treatment, it highlights the hormone as a promising target for future research, clinical trials, and strategies to slow ALS progression by leveraging the body’s natural protective systems.

DOI - https://doi.org/10.18632/aging.206298

Corresponding author - Peter H. King - phking@uabmc.edu

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

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Keywords - aging, fibroblast growth factor, 21 β-Klotho, ALS biomarker, human skeletal muscle, motor neurons

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FGF21 Muscle Hormone Associated with Slow ALS Progression and Extended Survival

Episode 196: The Importance of Second Opinions & the James Second Opinion Program, with Dr. Carrau

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/

HALP Score: Prognostic Ability in Cancers - A Literature Review

Oncotarget Podcast

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