BUFFALO, NY - April 8, 2025 – A new #editorial was #published in Oncotarget, Volume 16, on April 4, 2025, titled “Deep learning-based uncertainty quantification for quality assurance in hepatobiliary imaging-based techniques."

Dr. Yashbir Singh from Mayo Clinic and his colleagues discussed how artificial intelligence (AI) can improve liver imaging by recognizing when it might be wrong. This approach, called “uncertainty quantification,” helps clinicians better detect liver cancer and other diseases by pointing out areas in medical scans that need a second look. The authors explain how these AI tools could make imaging results more accurate and reliable, which is especially important when diagnosing serious conditions like liver tumors.

Liver and bile duct imaging is difficult because of the organ’s complex structure and differences in image quality. Even skilled radiologists can struggle to identify small or hidden tumors, especially in patients with liver damage or scarring. The editorial explains how new AI models not only read medical images but also measure their own confidence. When the AI system is unsure, it can alert clinicians to take a closer look. This extra layer of information can reduce missed diagnoses and improve early detection of liver cancer.

One of the most advanced tools described in the editorial is called AHUNet (Anisotropic Hybrid Network). This AI model works with both 2D and 3D images and can highlight which parts of a scan it is most confident about. It performed well when measuring the entire liver and showed how its confidence dropped when scanning smaller or multiple lesions. This feature helps clinicians know when more testing or review is needed.

The authors also looked at other AI models used in liver imaging. Some tools were able to analyze liver fat using ultrasound images and give clinicians both a result and a confidence score. Others improved the speed and accuracy of liver magnetic resonance imaging (MRI) scans, helping to create clear images in less time. These advancements could help hospitals work faster and provide better care.

The editorial highlights how this technology can be especially helpful in smaller clinics. If they do not have liver specialists, they could still use AI systems that flag uncertain results and send them to larger centers for review. Such an approach could improve care in rural or less-resourced areas.

“Radiology departments should develop standardized reporting templates that incorporate uncertainty metrics alongside traditional imaging findings.”

By using AI tools that know when to second-guess themselves, clinicians may soon have more reliable methods for detecting liver cancer and monitoring liver disease. The authors suggest that uncertainty-aware AI may soon become a vital part of everyday medical imaging, supporting faster and more accurate decisions in liver disease care.

DOI: https://doi.org/10.18632/oncotarget.28709

Correspondence to: Yashbir Singh — singh.yashbir@mayo.edu

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Keywords: cancer, deep learning, uncertainty quantification, radiology, hepatobiliary imaging

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Oncotarget

AI That Measures Its Own Uncertainty Could Improve Liver Cancer Detection

“We develop, evaluate and test interventions to help empower people to live healthier,” explained Roberto Benzo, PhD, an Ohio State health promotion and behavioral scientist and director of the James Lifestyle Lab. “We focus on empowering people to eat and exercise better and better manage their stress … helping people find the right solutions at the right time.” In this episode, Benzo explained how exercise, diet and managing stress are important for everyone, and for cancer patients during and after their treatment. “Even after a cancer diagnosis it’s not too late [to change behaviors],” Benzo said. “Being active and eating well can help you better tolerate your treatment and better manage your symptoms.” One of the tools Benzo and his team use re mobile health technologies such as iPhones, Fitbits and Apple Watches, as well as more accurate “research-grade” mobile technology applications.  “The data helps us better understand where people are at,” he said. “And helps us establish new goals and behaviors.” Benzo said it can be hard to change long-held lifestyle routines and he offered some tips … “Consistency is one of the top secrets. You don’t have to do a super-hard work out every day, consistency means doing something every day.”
“Acceptance and awareness of where you are is important, being at peace with where you are and not trying to push too hard to get to where you want to be.”
Goal setting … “but setting compassionate goals within your means.”
Social support … “having someone to help you, for emotional support, for informational support and someone to help you do things, such as exercising, and it may not be the same person for all three.”
Benzo’s overall goal is “to help people find acceptance, compassion [for themselves], patience and resilience and use this to help them and motivate them and feel less along, and find joy and contentment for what they do already have.”

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Episode 197: How the James Lifestyle Lab Improves the Lives of Cancer Patients, with Roberto Benzo

A conversation with science writer Philip Ball about his new illustrated history of alchemy

Elixirs, Experiments, and the Birth of Modern Science

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

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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.

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Keywords - aging, rapamycin, geroscience, longevity, healthspan

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Aging-US

Longevity & Aging Series (S3, E6): Girish Harinath

Poet and priest Spencer Reece joins Leader’s Way host Brandon Nappi for a moving conversation about the power of poetry as an act of remembrance, as a response to violence, and as a culture maker and culture keeper. Listen to Father Reece offer spontaneous recitation and remind us of the ways poetry can bring us closer to the Divine.   

Host: Brandon Nappi

Guest: Spencer Reece

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65: Poetry Holds Us Together with Spencer Reece

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

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Keywords - aging, lifespan, healthspan, Alk5 inhibitor, oxytocin, sex-specific differences

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Sex-Specific Effects Found in New Anti-Aging Therapy for Elderly Mice

BUFFALO, NY - October 1, 2025 – Oncotarget is proud to announce that its Editor-in-Chief, Wafik S. El-Deiry, MD, PhD, FACP, will chair the WIN Symposium as the Oncology Track of the Advancing Precision Medicine (APM) Annual Conference held October 3–4, 2025, at the Pennsylvania Convention Center in Philadelphia.

The WIN Consortium annual symposium featured as the Oncology Track of the APM Annual Conference 2025 unites global leaders in oncology, translational science, and precision medicine. This year’s program features keynote lectures, multi-track sessions– WIN Symposium, Multi-Omics Integration and Precision Medicine Outside of Oncology– and networking opportunities designed to accelerate the translation of research into clinical practice.

Highlights include:

--A keynote at opening of the WIN Symposium in Philadelphia by William G. Kaelin, Jr., MD — 2019 Nobel Laureate.

--Other luminaries in Oncology are speaking, including AACR President Lillian Siu, MD and AACR President-Elect Keith Flaherty, MD along with internationally recognized leaders in precision oncology.

--A world-class precision oncology molecular tumor board and oral presentations from the most competitive abstracts are part of the program.

--Multi-omics and disease-specific tracks spanning oncology, neurology, cardiovascular disease, rare disease, and infectious disease.

--Opportunities for collaboration among scientists, clinicians, industry innovators, and policymakers.

Registration is still open. Attendance is free for students, academic/government/non-profit participants, healthcare providers, and investors. The event provides CME credits. For full program details, visit the APM Annual Conference website.

About WIN Consortium:

WIN Consortium is a non-profit association headquartered in France. WIN was the first consortium that assembled all stakeholders of cancer care, from academia, industry, and patient advocates to work together across the globe. The WIN network assembles 34 world-class academic medical centers, industries, research organizations and patient advocates spanning 18 countries and 5 continents, aligned to launch trials to bolster Precision Oncology across the world. It was also the first organization to launch a N-of-One study using transcriptomics in addition to genomics to inform therapeutic choice in the WINTHER study.

WIN is the organizer of the WIN symposia in Precision Oncology.

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Wafik S. El-Deiry Chairs 2025 WIN Symposium in Collaboration with APM in Philadelphia

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

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Keywords - aging, lifespan, healthspan, Alk5 inhibitor, oxytocin, sex-specific differences

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New Anti-Aging Combo Boosts Lifespan in Old Male Mice

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

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Keywords - aging, frailty, rodents, frailty index, phenotype

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Standardizing Frailty Indexes to Improve Preclinical Aging Research

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

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Keywords - aging, Hutchinson-Gilford progeria syndrome (HGPS), progerin, microRNAs, adipogenesis

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Overactive MicroRNAs Block Fat Cell Development in Progeria

Dwight Zscheile is a professor of congregational mission and leadership at Luther Seminary, and his wife, Blair Pogue, is a priest and canon for vitality and innovation in the Episcopal Church in Minnesota. They join Leader’s Way host Brandon Nappi for a conversation about their joint passion for engaging the innovative ways the Church is renewing its commitment to community and communion by meeting people where they are.  Brandon talks with Dwight and Blair about their new book, Embracing the Mixed Ecology: Inherited and New Forms of Christian Community Flourishing Together, which unpacks the theological language of “mixed ecology,” and how this language can help us imagine what is possible in our church communities.

Host: Brandon Nappi

Guests: Dwight Zscheile and Blair Pogue

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Embracing the Mixed Ecology of the Church with Dwight Zscheile and Blair Pogue

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/

AI That Measures Its Own Uncertainty Could Improve Liver Cancer Detection

Oncotarget Podcast