BUFFALO, NY — June 4, 2025 — A new #editorial was #published in Aging (Aging-US) Volume 17, Issue 5, on May 29, 2025, titled “Rethinking healthcare through aging biology.”

In this scientific editorial, Aging (Aging-US) Editor-in-Chief Marco Demaria from the European Research Institute for the Biology of Ageing (ERIBA), University Medical Center Groningen (UMCG) and the University of Groningen (RUG), advocates for healthcare reform that addresses the biological drivers of aging rather than individual chronic conditions. The article proposes that targeting the root causes of age-related diseases through aging biology could revolutionize preventive care, extend healthspan, and reduce long-term healthcare costs. This proactive approach aligns with a growing body of aging research focused on improving healthy longevity.

Dr. Demaria explains that today’s disease-focused model is inadequate for aging populations, who often suffer from multimorbidity—the presence of multiple chronic illnesses like cancer, heart disease, and type 2 diabetes. These overlapping conditions, rooted in common aging mechanisms, overwhelm healthcare systems and lead to complex treatments with limited success. The editorial suggests that identifying and intervening in the biological aging process could prevent such diseases before they emerge.

In the editorial, Dr. Demaria outlines three healthcare paradigms. The first is the existing system, which reacts to disease after symptoms appear. The second involves intervening once age-related damage begins, using new tools such as senolytics, which eliminate harmful senescent cells, and rapalogs, which regulate cellular metabolism. The third and most forward-looking model focuses on preventing aging-related damage before it starts. This strategy supports lifelong biological balance and seeks to avoid early molecular decline through continuous health maintenance.

Prevention is key in this model. Lifestyle choices—such as exercise, a healthy diet, quality sleep, and stress reduction—play a vital role in slowing the aging process. Dr. Demaria also points to the promise of biological age diagnostics—tools or tests that estimate a person’s biological age—which allow people to track their physiological aging and adopt personalized interventions. Additionally, optimizing maternal nutrition and early-life health can contribute to lifelong disease prevention.

To support this shift, the editorial calls for major changes in medical education. Physicians must be trained in geroscience, healthspan optimization, and personalized preventive care. This knowledge will prepare future clinicians not just to treat disease, but to delay or prevent it altogether. Collaboration among healthcare providers, researchers, and policymakers will be essential for building this new system.

​​“The third paradigm—preventing aging-related damage—demands a systemic shift toward predictive and preventative research, with an emphasis on multi-omic data, lifestyle interventions, and early-life interventions.”

By redefining medicine around the science of aging, Dr. Demaria’s editorial highlights the path toward healthier aging, longer life expectancy, and a more sustainable healthcare future.

DOI - https://doi.org/10.18632/aging.206262

Corresponding author - Marco Demaria - m.demaria@umcg.nl

Video short - https://www.youtube.com/watch?v=xR-16cjHnQY

To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us on social media at:

Facebook - https://www.facebook.com/AgingUS/
X - https://twitter.com/AgingJrnl
Instagram - https://www.instagram.com/agingjrnl/
YouTube - https://www.youtube.com/@AgingJournal
LinkedIn - https://www.linkedin.com/company/aging/
Bluesky - https://bsky.app/profile/aging-us.bsky.social
Pinterest - https://www.pinterest.com/AgingUS/
Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc

MEDIA@IMPACTJOURNALS.COM

Aging (Aging-US)

New Vision for Healthcare Focuses on Preventing Aging-Related Diseases

BUFFALO, NY - June 4, 2025 – A new #research paper was #published in Volume 16 of Oncotarget on May 20, 2025, titled “Targeting PCNA/AR interaction inhibits AR-mediated signaling in castration resistant prostate cancer cells."

In this study, authors Shan Lu and Zhongyun Dong from the University of Cincinnati College of Medicine investigated how interfering with a protein interaction could reduce prostate cancer growth. Their study based on prostate cancer cells shows that blocking the link between PCNA, a protein important for DNA repair, and the androgen receptor (AR), which drives prostate cancer growth, can slow down cancer cell multiplication. This discovery could lead to a new treatment for patients with advanced prostate cancer, particularly those no longer responding to hormone therapy.

Prostate cancer is one of the most common cancers in men. Many patients eventually become resistant to hormone treatment. In this advanced stage, called castration-resistant prostate cancer (CRPC), tumors continue to grow by using either the full-length androgen receptor (AR-FL) or altered versions called AR variants (AR-Vs). This study shows that the interaction between AR and PCNA helps both AR-FL and AR-Vs remain active, supporting cancer cell survival and growth.

The researchers identified a new region in the AR that binds to PCNA. They developed a small peptide, R9-AR-PIP, to mimic this region and block the AR-PCNA connection. They found that this peptide reduced AR’s ability to bind DNA and lowered the levels of key genes involved in cancer cell growth. Importantly, the peptide was effective against both types of AR, including the variant forms that are especially challenging in CRPC.

“We identified a second PIP-box (PIP-box592) in the DNA binding domain of AR and found that dihydrotestosterone enhances the binding of full-length AR (AR-FL) but not a constitutively active variant (AR-V7) to PCNA.”

They also tested a small molecule, PCNA-I1S, which interferes with PCNA’s ability to move to the cell nucleus and interact with AR. This molecule showed similar effects as the peptide, reducing AR activity and stopping cancer cell growth. Together, these findings suggest that targeting PCNA/AR interactions could be a promising strategy to fight CRPC, especially in patients with limited treatment options.

One key result was that both the peptide and the small molecule reduced the levels of cyclin A2, a protein that helps cells divide and is often overexpressed in CRPC. Since this protein is linked to patients' poor outcomes, its reduction could be especially beneficial.

This study improves our understanding of how prostate cancer continues to grow even after hormone treatments fail. By blocking a crucial helper of the androgen receptor, researchers have uncovered a new way to potentially slow or stop the disease. Further studies in animal models are needed, but this approach could lead to more effective treatments for men with advanced prostate cancer.

DOI - https://doi.org/10.18632/oncotarget.28722

Correspondence to - Zhongyun Dong - dongzu@ucmail.uc.edu

Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28722

Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/

Keywords - cancer, PCNA, androgen receptor, PCNA inhibitors, AR splicing variants, CRPC

To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:

Facebook - https://www.facebook.com/Oncotarget/
X - https://twitter.com/oncotarget
Instagram - https://www.instagram.com/oncotargetjrnl/
YouTube - https://www.youtube.com/@OncotargetJournal
LinkedIn - https://www.linkedin.com/company/oncotarget
Pinterest - https://www.pinterest.com/oncotarget/
Reddit - https://www.reddit.com/user/Oncotarget/
Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh

MEDIA@IMPACTJOURNALS.COM

Oncotarget

Targeting PCNA-Androgen Receptor Interaction Suppresses Prostate Cancer Cell Growth

Researchers at Brown University have developed a combination treatment that significantly increases survival in mice with glioblastoma (GBM), a highly aggressive and treatment-resistant brain cancer. The approach uses a new class of drugs called imipridones along with radiation therapy and standard chemotherapy. This triple therapy, known as IRT, was recently detailed in a study published in Oncotarget.

Understanding Glioblastoma and the Need for Better Therapies

Glioblastoma is the most common and aggressive malignant brain tumor in adults. It grows quickly and is difficult to treat, often leading to poor outcomes. Most patients survive less than 15 months after diagnosis, even when treated with surgery, radiation, and the chemotherapy drug temozolomide (TMZ). This treatment may slow the disease, but it does not typically stop it.

Full blog - https://www.oncotarget.org/2025/06/04/experimental-triple-therapy-improves-survival-in-glioblastoma-mouse-model/

Paper DOI - https://doi.org/10.18632/oncotarget.28707

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

Video short - https://www.youtube.com/watch?v=Q_mXy8mana0

Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28707

Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/

Keywords - cancer, glioblastoma multiforme, IDH, ONC201, ONC206, MGMT, temozolomide, radiotherapy

To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:

Facebook - https://www.facebook.com/Oncotarget/
X - https://twitter.com/oncotarget
Instagram - https://www.instagram.com/oncotargetjrnl/
YouTube - https://www.youtube.com/@OncotargetJournal
LinkedIn - https://www.linkedin.com/company/oncotarget
Pinterest - https://www.pinterest.com/oncotarget/
Reddit - https://www.reddit.com/user/Oncotarget/
Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh

MEDIA@IMPACTJOURNALS.COM

Experimental Triple Therapy Improves Survival in Glioblastoma Mouse Model

Dr. Stefanie Morgan joins Dr. Robert Dudley from AgelessRx to discuss a #research paper she co-authored that was #published in Volume 17, Issue 4 of Aging, entitled “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

Author interview - https://www.youtube.com/watch?v=2qlIiVh2OJs

Video short - https://www.youtube.com/watch?v=z5j2nyK2HZ8

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.

Sign up for free Altmetric alerts about this article - 
https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206235

Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts

Keywords - aging, rapamycin, geroscience, longevity, healthspan

To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us on social media at:

Facebook - https://www.facebook.com/AgingUS/
X - https://twitter.com/AgingJrnl
Instagram - https://www.instagram.com/agingjrnl/
YouTube - https://www.youtube.com/@AgingJournal
LinkedIn - https://www.linkedin.com/company/aging/
Bluesky - https://bsky.app/profile/aging-us.bsky.social
Pinterest - https://www.pinterest.com/AgingUS/
Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc

MEDIA@IMPACTJOURNALS.COM

Behind the Study: Rapamycin’s 1-Year Impact on Healthspan—PEARL Trial Results

BUFFALO, NY – June 9, 2025 – A new #research paper was #published in Volume 16 of Oncotarget on May 20, 2025, titled “Cigarette smoke and decreased DNA repair by Xeroderma Pigmentosum Group C use a double hit mechanism for epithelial cell lung carcinogenesis.”

In this study, led by first author Nawar Al Nasralla and corresponding author Catherine R. Sears, from the Division of Pulmonary, Critical Care, Sleep and Occupational Medicine, Indianapolis and the Richard L. Roudebush Veterans Affairs Medical Center, researchers investigated how cigarette smoke and reduced DNA repair capacity contribute together to the development of lung cancer. They found that when a critical DNA repair protein called XPC is decreased and lung cells are exposed to cigarette smoke, the combination causes extensive damage and significantly increases cancer risk.

Non-small cell lung cancer (NSCLC) develops through both genetic and environmental factors. This study focused on how cigarette smoke affects the body’s natural ability to repair DNA. The researchers studied the role of XPC, a protein essential for recognizing and repairing harmful DNA changes caused by tobacco smoke. They found that low levels of XPC — commonly seen in lung cancer patients — made lung cells less capable of repairing DNA. This made the cells unstable and more likely to become cancerous. These changes were most pronounced in normal lung cells, suggesting that the earliest stages of disease occur before cancer is even detected.

The findings support a “double hit” model, where both cigarette smoke and reduced DNA repair work together to drive cancer development. In laboratory experiments, normal lung cells with low XPC levels showed more damage and cell death after cigarette smoke exposure. By contrast, lung cancer cells were more resistant to smoke damage, even when XPC was low, indicating that critical changes had likely occurred earlier in the disease process.

“Our study suggests that cigarette smoke exposure leads to decreased XPC mRNA expression, exacerbates total and oxidative DNA damage, hinders NER, and may contribute to lung cancer development.”

The study also showed that DNA repair ability declined significantly in healthy cells after smoke exposure, but this effect was not seen in cancer cells. In addition, the researchers confirmed that XPC gene activity was lower in actual lung tumor tissue compared to nearby healthy lung tissue. This pattern was consistent across both adenocarcinoma and squamous cell carcinoma, the two main types of NSCLC.

These results add to our understanding of how lung cancer begins at the molecular level. By showing how cigarette smoke and reduced DNA repair combine to create genetic instability, the research points toward new strategies for prevention. A better understanding of XPC’s role could help identify high-risk individuals and inform future efforts to stop lung cancer before it begins.

DOI - https://doi.org/10.18632/oncotarget.28724

Correspondence to - Catherine R. Sears - crufatto@iu.edu

Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28724

Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/

Keywords - cancer, DNA repair, DNA damage, lung adenocarcinoma, squamous cell carcinoma, Xeroderma Pigmentosum Group C (XPC)

To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:

Facebook - https://www.facebook.com/Oncotarget/
X - https://twitter.com/oncotarget
Instagram - https://www.instagram.com/oncotargetjrnl/
YouTube - https://www.youtube.com/@OncotargetJournal
LinkedIn - https://www.linkedin.com/company/oncotarget
Pinterest - https://www.pinterest.com/oncotarget/
Reddit - https://www.reddit.com/user/Oncotarget/
Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh

MEDIA@IMPACTJOURNALS.COM

Cigarette Smoke and DNA Repair Deficiency Drive Lung Cancer Development

BUFFALO, NY — June 10, 2025 — A new #research perspective was #published in Aging (Aging-US) Volume 17, Issue 5, on May 5, 2025, titled “Methylation clocks for evaluation of anti-aging interventions.”

In this perspective article, Dr. Josh Mitteldorf explores how current epigenetic clocks—used to estimate biological age—might mislead scientists trying to evaluate anti-aging therapies. The paper challenges a widespread assumption: that all changes in DNA methylation with age are equally valid for measuring biological decline. Dr. Mitteldorf proposes that failing to distinguish between different types of epigenetic changes could lead to inaccurate conclusions, potentially even favoring treatments that reduce repair processes rather than extend healthy lifespan.

Methylation clocks have become a popular tool in aging research. These clocks use patterns of DNA methylation, a form of gene regulation that changes over time, to predict a person’s biological age. Because human aging trials are long and expensive, these clocks offer a faster way to evaluate whether a therapy slows or reverses aging. However, this article warns that not all methylation changes are equal in meaning or effect.

The perspective identifies two main categories of methylation changes that occur with age. One type, called 'Type 1,' seems to support the idea that aging may be programmed, with gene activity changing in ways that could cause damage, such as more inflammation or increased cell loss. The second type, “Type 2,” involves increased gene activity aimed at repairing age-related damage. If a therapy reduces the activity of Type 2 genes, it may appear to slow aging while actually interfering with the body’s repair response.

“Paradoxically, an intervention that “sets back” the body’s methylation clock to a younger state is shutting off vital repair mechanisms, so it is likely inimical to health and longevity.” 

This distinction is important because most methylation clocks, including popular models like GrimAge, do not separate these two types. As a result, they may incorrectly suggest that a treatment is reversing aging when it is only suppressing beneficial repair mechanisms. According to Dr. Mitteldorf, this could lead researchers to draw the wrong conclusions and unintentionally slow down progress in anti-aging research.

The author also addresses a growing trend in the scientific community that aims to explain age-related methylation as random drift rather than directed change. In a pilot analysis using publicly available data, Dr. Mitteldorf attempted to construct a clock based purely on stochastic, or random, changes. The results showed a weak correlation with age, suggesting that random drift is an unreliable basis for assessing biological aging.

Dr. Mitteldorf argues that most age-related methylation changes are likely intentional and regulated, rather than random. If so, epigenetic clocks must be refined to reflect the biological purpose behind methylation shifts. Without distinguishing between changes that indicate damage and those that indicate repair, current clocks may not only mismeasure age but also misguide intervention strategies.

This article highlights the urgent need to improve how methylation data are interpreted before such clocks can reliably assess anti-aging therapies. A clearer understanding of these molecular patterns could help reshape the future of aging research and therapy evaluation.

DOI - https://doi.org/10.18632/aging.206245

Corresponding author - Josh Mitteldorf - aging.advice@gmail.com

To learn more about the journal, please visit our website at https://www.Aging-US.com.

MEDIA@IMPACTJOURNALS.COM

Why Epigenetic Clocks May Fail to Measure Anti-Aging Effects

BUFFALO, NY - June 11, 2025 – A new #research paper was #published in Volume 16 of Oncotarget on May 29, 2025, titled “Durable complete response in leptomeningeal disease of EGFR mutated non-small cell lung cancer to amivantamab, an EGFR-MET receptor bispecific antibody, after progressing on osimertinib.”

A team led by first author Jinah Kim, from the University of Vermont Medical Center, and corresponding author Young Kwang Chae, from the Feinberg School of Medicine, reports a clinical case in which a patient with advanced non-small cell lung cancer (NSCLC) carrying rare EGFR mutations responded remarkably to amivantamab after other treatments had failed. The patient experienced a complete resolution of brain and spinal fluid metastases, suggesting that amivantamab may be a viable option for patients with uncommon genetic profiles and limited therapy options.

Lung cancer remains one of the leading causes of cancer-related deaths worldwide. Patients with NSCLC who have rare mutations in the EGFR gene often face limited treatment options and poor outcomes, especially when the disease spreads to the brain or spinal fluid. This case involved a 67-year-old man diagnosed with NSCLC who had two rare EGFR mutations—G719A and A289V. After disease progression on osimertinib and other therapies, the patient began amivantamab monotherapy.

Within six weeks, his lung tumor shrank by over 30 percent. By six months, imaging confirmed the disappearance of brain metastases and leptomeningeal disease, a serious condition affecting the membranes of the brain and spinal cord. Blood tests showed no detectable cancer-related mutations, and the patient, previously wheelchair-bound, regained the ability to walk and perform daily activities. This response has been sustained for more than 19 months.

 “Treatment produced a durable response over 19 months, including a 32.2% reduction in tumor size at six weeks, and complete resolution of brain metastases and LMD by six months.”

Amivantamab is a bispecific antibody that targets EGFR and MET, two key drivers of tumor growth. While it is approved in combination regimens for common EGFR mutations, its effectiveness as a single agent in rare mutations or in treating brain metastases remains largely unproven. This case challenges the assumption that large antibody drugs cannot cross the blood-brain barrier and suggests that amivantamab may have potential in managing central nervous system involvement. Further research is needed to clarify how the drug achieves these effects and to explore its broader use in patients with rare EGFR mutations and limited treatment options.

This case highlights three key findings: amivantamab may be effective against rare EGFR mutations, can be used as monotherapy, and may overcome the challenges of the blood-brain barrier. Although based on a single patient, the results provide encouraging evidence to support further investigation of amivantamab in treating difficult-to-manage forms of NSCLC.

DOI - https://doi.org/10.18632/oncotarget.28730

Correspondence to - Young Kwang Chae - young.chae@northwestern.edu

Video short - https://www.youtube.com/watch?v=RJX3rmtH7h8

Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/

Keywords - cancer, amivantamab, monotherapy, rare EGFR mutation, NSCLC, leptomeningeal disease

To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:

Facebook - https://www.facebook.com/Oncotarget/
X - https://twitter.com/oncotarget
Instagram - https://www.instagram.com/oncotargetjrnl/
YouTube - https://www.youtube.com/@OncotargetJournal
LinkedIn - https://www.linkedin.com/company/oncotarget
Pinterest - https://www.pinterest.com/oncotarget/
Reddit - https://www.reddit.com/user/Oncotarget/
Spotify - https://open.spotify.com/show/0gRwT6BqYWJzxzmjPJwtVh

MEDIA@IMPACTJOURNALS.COM

Rare Non-Small Cell Lung Cancer with Brain Metastases Responds to Amivantamab Monotherapy

As we age, our brains become more sensitive to stress and disease. A recent study sheds light on a lesser-known risk: reduced oxygen levels. The study, titled “Defining the hypoxic thresholds that trigger blood-brain barrier disruption: the effect of age” and recently published as the cover for Volume 17, Issue 5 of Aging (Aging-US), found that low oxygen—also called hypoxia—can harm the aging brain by disrupting the blood-brain barrier (BBB). This damage may contribute to cognitive decline, memory problems, and an increased risk of dementia.

Understanding Hypoxia in the Brain

The brain relies on a steady supply of oxygen to stay healthy. When oxygen levels fall—a condition known as hypoxia—the brain undergoes changes to adapt. These changes include the remodeling of blood vessels and, importantly, a weakening of the blood-brain barrier. The BBB acts as a filter, protecting brain tissue from harmful substances. When it breaks down, it can lead to inflammation, brain cell damage, and cognitive issues.

Hypoxia is common in older adults, especially those with conditions like sleep apnea, chronic obstructive pulmonary disease (COPD), heart failure, and asthma. That is why understanding the connection between low oxygen and the aging brain is crucial for preventing long-term neurological damage.

Full blog - https://aging-us.org/2025/06/oxygen-deprivation-and-the-aging-brain-a-hidden-trigger-for-cognitive-decline/

Paper DOI - https://doi.org/10.18632/aging.206241

Corresponding author - Richard Milner - rmilner@sdbri.org

Video short - https://www.youtube.com/watch?v=Nr6rTm7aJRo

Sign up for free Altmetric alerts about this article - 
https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206241

Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts

Keywords - aging, blood-brain barrier integrity, endothelial, proliferation, microglia, chronic mild hypoxia, hypoxic threshold

To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us:

Facebook - https://www.facebook.com/AgingUS/
X - https://twitter.com/AgingJrnl
Instagram - https://www.instagram.com/agingjrnl/
YouTube - https://www.youtube.com/@AgingJournal
LinkedIn - https://www.linkedin.com/company/aging/
Bluesky - https://bsky.app/profile/aging-us.bsky.social
Pinterest - https://www.pinterest.com/AgingUS/
Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc

MEDIA@IMPACTJOURNALS.COM

Oxygen Deprivation and the Aging Brain: A Hidden Trigger for Cognitive Decline

BUFFALO, NY — June 12, 2025 — A new #research paper was #published in Aging (Aging-US) Volume 17, Issue 5, on May 3, 2025, titled “APOE genotype and biological age impact inter-omic associations related to bioenergetics.”

In this study, led by first author Dylan Ellis and corresponding author Noa Rappaport from the Institute for Systems Biology, researchers discovered that different versions of the APOE gene—particularly ε2 and ε4—are linked to metabolic patterns associated with aging and Alzheimer’s disease risk. Both variants were linked to increased levels of diacylglycerols, a type of fat molecule connected to insulin resistance and inflammation, suggesting shared disruptions in how the body regulates energy.

The research team analyzed data from over 2,200 adults without an Alzheimer’s diagnosis, exploring how APOE genotypes influence biological age, a measure of health that reflects how quickly or slowly someone is aging at a cellular level. They found that the same metabolic disturbances seen in ε2 carriers were also present in people considered biologically older, revealing unexpected overlap between genetic risk and aging-related metabolic changes.

To examine these connections in more detail, the researchers used a multi-omics approach, combining blood-based metabolism and protein data, gut bacteria analysis from stool samples, and clinical chemistry data. This method allowed them to map how genetic differences and biological aging affect the body’s energy systems. They observed altered connections between glucose metabolism, inflammatory markers, and key molecules that play roles in energy production, indicating early disruptions that could contribute to age-related diseases.

One of the study’s surprising findings was that the ε2 variant, usually associated with longer life and reduced Alzheimer’s risk, showed metabolic traits similar to those found in insulin-resistant individuals. This suggests that ε2 may carry metabolic disadvantages earlier in life, with its protective effects becoming more pronounced later. Conversely, ε4—linked to greater Alzheimer’s risk—may exert its influence based on interactions with lifestyle factors like diet, sex, and overall health status.

“‘Omics association patterns of ε2-carriers and increased biological age were also counter-intuitively similar, displaying significantly increased associations between insulin resistance markers and energy-generating pathway metabolites.”

By identifying these shared biological signatures, this study offers a new framework for understanding how genes and metabolism work together to influence aging. These findings could support more personalized health strategies aimed at delaying biological aging and reducing the risk of chronic diseases. As aging populations grow worldwide, understanding these pathways is essential to improving healthspan.

DOI - https://doi.org/10.18632/aging.206243

Corresponding author - Noa Rappaport - noa.rappaport@isbscience.org

Video short - https://www.youtube.com/watch?v=75hZQoO5U0U

Sign up for free Altmetric alerts about this article - 
https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206243

Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts

Keywords - aging, apolipoprotein E (APOE), biological age, metabolism, Alzheimer’s disease (AD), insulin resistance

To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us on social media at:

Facebook - https://www.facebook.com/AgingUS/
X - https://twitter.com/AgingJrnl
Instagram - https://www.instagram.com/agingjrnl/
YouTube - https://www.youtube.com/@AgingJournal
LinkedIn - https://www.linkedin.com/company/aging/
Bluesky - https://bsky.app/profile/aging-us.bsky.social
Pinterest - https://www.pinterest.com/AgingUS/
Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc

MEDIA@IMPACTJOURNALS.COM

APOE Gene Variants Linked to Metabolic Signatures of Aging and Alzheimer's Risk

Recorded at Aviianstudios Houston, Texas
Mixed and Mastered by Sarweezy

A Raw story track about my life, also inspiring messages with gems being dropped, listen carefully as the lesson, story, and rhyme schemes are all there greatly for your enjoyment.


this is a worthwhile listen if you like eminem or nipsey hussle.


Mastermind a Million

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