Aging-US

BUFFALO, NY — December 3, 2025 — A new #essay was #published in Volume 17, Issue 11 of Aging-US on November 19, 2025, titled “On the intergenerational transfer of ideas in aging and cancer research: from the hypothalamus according to V.M. Dilman to the mTOR protein complex according to M.V. Blagosklonny.”

In this work, Aleksei G. Golubev from the N.N. Petrov National Medical Research Center of Oncology reflects on the legacy of two influential Russian scientists, Vladimir M. Dilman and his son Mikhail V. Blagosklonny, who each introduced groundbreaking ideas about aging and cancer. Drawing from his own experience working in Dilman’s lab, Golubev explores how their ideas remain deeply relevant to today’s scientific understanding.

The essay connects Dilman’s “elevation theory” with Blagosklonny’s “hyperfunction theory,” two frameworks that challenge the conventional view of aging as a process of decline. Instead, both propose that aging results from continued biological processes that once supported growth but eventually become harmful when left unchecked.

Dilman believed that aging begins with reduced sensitivity in the hypothalamus, a brain region that regulates the body’s balance. This desensitization disrupts metabolism and hormone levels, setting the stage for many chronic illnesses. Decades later, Blagosklonny expanded on this idea at the molecular level. Central to his theory is the mTOR protein complex, which regulates growth and metabolism and is now a major focus in aging research.

Golubev also explores the historical and personal connections between the two scientists. Dilman, an endocrinologist trained in the Soviet Union, and Blagosklonny, a molecular biologist educated during the post-Soviet period, represent two generations shaped by a shared scientific tradition.

“Dilman’s scientific legacy is not as well recognized as it should be, partly due to bias in citation practices.”

The essay also draws attention to a troubling trend in science: the tendency to overlook early contributions, especially from non-Western scholars. Many of Dilman’s insights, such as the connection between high blood sugar, insulin resistance, and cancer, have since been validated by modern tools, yet his work is rarely cited. Golubev points out how citation practices, language barriers, and historical isolation have contributed to this lack of recognition.

Finally, Golubev encourages the scientific community to look back and acknowledge the foundational work that shaped modern aging science. It also highlights the importance of cross-generational knowledge in moving science forward. By tracing the intellectual journey from hormonal regulation in the brain to molecular pathways in cells, this essay demonstrated the relevance of old ideas in a new biological era.

DOI - https://doi.org/10.18632/aging.206338

Corresponding author - Aleksei G. Golubev - [email protected]

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

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Keywords - aging, gerontology, history of science, hyperfunction, mTOR, hypothalamus, cancer, metabolism, immunity

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BUFFALO, NY — December 1, 2025 — A new #research paper featured on the #cover of Volume 17, Issue 11 of Aging-US was #published on October 30, 2025, titled “SAMP-Score: a morphology-based machine learning classification method for screening pro-senescence compounds in p16 positive cancer cells.”

In this study led by first author Ryan Wallis along with corresponding author Cleo L. Bishop, from Queen Mary University of London, researchers developed a machine learning tool to identify compounds that induce cancer cells into senescence. The tool, called SAMP-Score, offers a new strategy for drug discovery in cancers with poor treatment options like basal-like breast cancer.

Senescence is a process where damaged or aged cells stop dividing. In cancer therapy, inducing senescence is an approach to control tumor growth. However, it is difficult to detect true senescence in cancer cells that already appear aged. These cancers, often called Sen-Mark+ cancers, include basal-like breast cancer and typically lack reliable markers to confirm senescence. SAMP-Score was designed to address this problem.

Instead of relying on traditional markers, the researchers built a machine learning model trained to recognize patterns based on senescent cells’ shape and structure under a microscope. These visual patterns, known as senescence-associated morphological profiles (SAMPs), allowed the model to distinguish real signs of aging from other effects such as toxicity or normal variation. By analyzing thousands of cell images, the model learned to classify whether a cell had truly entered senescence.

“To demonstrate the potential application of SAMP-Score in p16 positive cancer therapeutic discovery, we assessed a diversity screen of 10,000 novel chemical entities in MB-468 cells (p16 positive BLBC).”

The team used SAMP-Score to screen more than 10,000 experimental compounds. One compound, QM5928, consistently triggered senescence in several cancer cell types without killing them, making it a promising candidate for further study. Importantly, it worked in cancers resistant to known drugs like palbociclib, which are often ineffective in cancers with high p16 expression like basal-like breast cancer.

Further analysis revealed that QM5928 caused the p16 protein to move into the nucleus of cancer cells, a possible sign that the protein is helping stop cell division. This subtle effect was only detectable using the detailed imaging and analysis made possible by SAMP-Score, highlighting the tool’s ability to distinguish true senescence from toxic responses and making it a powerful resource in cancer drug discovery.

By combining machine learning with high-resolution imaging, this study introduces a new way to find and evaluate cancer therapies. SAMP-Score could accelerate efforts to develop treatments that exploit the body’s natural aging processes to fight cancer, especially for patients with resistant tumors. The tool is openly available at GitHub, making it accessible for other researchers exploring senescence-based cancer therapies.

DOI - https://doi.org/10.18632/aging.206333

Corresponding author - Cleo L. Bishop - [email protected]

Abstract video - https://www.youtube.com/watch?v=qXI_KI3EgHE

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Interest in healthier, longer lives is rising, supported by recent scientific advances in aging research. But turning those discoveries into everyday healthcare solutions remains a work in progress. In this landscape, longevity clinics have attracted attention as personalized alternatives to traditional medicine.

What Are Longevity Clinics?

Longevity clinics are private centers offering tailored programs designed to improve long-term health and slow biological aging. Using advanced diagnostics such as genetic sequencing, full-body imaging, and blood tests, they develop personalized plans that may include exercise, nutrition, hormone therapy, or experimental treatments. Frequently found in countries like the United States, Switzerland, and the United Arab Emirates, these clinics reflect a growing global interest in preventive healthcare, though their high costs and scientific credibility remain subjects of debate.

The Editorial

“Longevity clinics: between promise and peril,” an editorial by Marco Demaria, Editor-in-Chief of Aging-US, from the European Research Institute for the Biology of Ageing (ERIBA), University Medical Center Groningen (UMCG), University of Groningen (RUG), was published in Aging-US (Volume 17, Issue 10).

Full blog - https://aging-us.org/2025/11/longevity-clinics-balancing-innovation-with-regulation/

Paper DOI - https://doi.org/10.18632/aging.206330

Corresponding author - Marco Demaria — [email protected]

Abstract video - https://www.youtube.com/watch?v=Bt84xBdii0s

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Keywords - aging, longevity clinics, biomarkers, frailty, senescence

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BUFFALO, NY — November 25, 2025 — A new #research paper was #published in Volume 17, Issue 10 of Aging-US on October 13, 2025, titled “Hospitalization with infections and risk of Dementia: a systematic review and meta-analysis.”

This large-scale meta-analysis, led by first author Wei Yu Chua from the National University of Singapore and corresponding author Eng-King Tan from the National Neuroscience Institute and Duke-NUS Medical School in Singapore, shows that adults hospitalized with infections have a significantly higher risk of developing dementia. The findings are especially important as global populations grow older and hospitalizations for infections increase, highlighting a potential new approach for dementia prevention.

“Out of 1900 studies that were screened initially, 16 studies comprising 4,266,276 patients were included for analysis.”

The researchers analyzed data from over 4 million individuals across 16 studies, making this study the most comprehensive review to date on the association between infection-related hospital stays and long-term brain health. The results showed that being hospitalized for an infection raised the risk of all-cause dementia by 83%. Among the types of infections studied, sepsis carried the highest risk, followed by pneumonia, urinary tract infections, and skin or soft tissue infections. The risk of developing vascular dementia was notably higher than that of Alzheimer’s disease.

One possible explanation for the association between infections and dementia is that infections trigger systemic inflammation that may reach the brain. Inflammatory molecules can cross the blood-brain barrier, potentially leading to the buildup of damaging proteins and the death of brain cells. This process may be more severe in older adults, whose immune systems are often slower to respond and recover. The study also suggests that even a single infection-related hospitalization can speed up cognitive decline, especially in individuals already at higher risk.

Importantly, the risk of dementia was greatest within the first year following an infection but remained elevated for many years afterward. In fact, studies with follow-ups longer than a decade showed even stronger associations. These results suggest the need for early cognitive monitoring after hospital discharge, particularly in older adults recovering from infections.

These findings have important implications for healthcare systems, particularly those serving aging populations, and underscore the lasting impact that infections can have on the brain. This research highlights the importance of looking beyond genetics and lifestyle for prevention strategies. With over 50 million people affected by dementia worldwide and annual care costs in the U.S. exceeding $300 billion, identifying new and preventable risk factors is critical. Reducing infections, improving hospital care, and monitoring brain health after illness may offer promising ways to protect cognitive function in aging populations.

DOI - https://doi.org/10.18632/aging.206329

Corresponding author - Eng-King Tan - [email protected]

Abstract video - https://www.youtube.com/watch?v=uyv5VHHHIA4

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BUFFALO, NY — November 20, 2025 — A new #research paper was #published in Volume 17, Issue 10 of Aging-US on October 10, 2025, titled “Developmental arrest rate of an embryo cohort correlates with advancing reproductive age, but not with the aneuploidy rate of the resulting blastocysts in good prognosis patients: a study of 25,974 embryos.”

In this large-scale study, Andres Reig of the IVIRMA Global Research Alliance and Robert Wood Johnson Medical School, along with Emre Seli of the IVIRMA Global Research Alliance and Yale School of Medicine, investigated how female age and chromosomal abnormalities affect embryo development in patients undergoing in vitro fertilization (IVF). They found that embryo developmental arrest (EDA) becomes more common as women age. However, this arrest is not directly associated with the presence of chromosomal errors in the embryos that continue to develop. These findings could help improve fertility counseling and treatment strategies.

The researchers analyzed 25,974 embryos from 1,928 IVF cycles, all from patients with a good chance of success. The study showed that the percentage of embryos that stopped developing before reaching the blastocyst stage increased with age: from 33% in women under 35 to 44% in those over 42. Despite this rise, the rate of chromosomal abnormalities, known as aneuploidy, in the embryos that did reach the blastocyst stage did not show a strong connection with the rate of arrest after adjusting for age.

This distinction is important because both developmental arrest and aneuploidy reduce the number of embryos suitable for transfer. But this study suggests they are caused by different biological processes. In other words, an embryo may stop developing even if it has the correct number of chromosomes, and some embryos with chromosomal abnormalities may still grow to the blastocyst stage.

“A very weak positive correlation was identified between EDA rate and the rate of aneuploidy (r: 0.07, 95% CI 0.03–0.11; R2: 0.00, p < 0.01) when evaluating all cohorts.”

The authors suggest that other factors, such as the health of the egg’s mitochondria or mutations in maternal-effect genes, may explain why some embryos stop developing. These insights could help researchers identify new ways to improve embryo quality, especially for older women undergoing IVF.

Importantly, the study focused on embryos that developed far enough to be tested, which helped avoid technical problems that come with analyzing arrested embryos directly. This approach allowed for more reliable comparisons across age groups and embryo quality.

Overall, the study highlights the importance of maternal age as a key factor in embryo development, independent of chromosomal results. It also opens new directions for research, aiming to better understand why embryos fail to develop and how this knowledge might lead to improved fertility treatments in the future.

DOI - https://doi.org/10.18632/aging.206328

Corresponding author - Emre Seli - [email protected]

Abstract video - https://www.youtube.com/watch?v=g0oS3HBNmuQ

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Keywords - aging, ovarian aging, reproductive aging, embryonic arrest, embryonic aneuploidy, developmental arrest

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BUFFALO, NY — November 18, 2025 — A new #research paper was #published in Volume 17, Issue 10 of Aging-US on October 3, 2025, titled “Growth hormone excess drives liver aging via increased glycation stress.”

In this study, led by first author Parminder Singh alongside with corresponding authors Pankaj Kapahi from the Buck Institute for Research on Aging and Andrzej Bartke from Southern Illinois University School of Medicine, researchers investigated how elevated growth hormone (GH) levels contribute to liver aging and dysfunction. They found that excess GH disrupts liver metabolism in ways that resemble aging-related liver damage. The study suggests that managing glycation stress may help prevent or treat liver diseases linked to abnormal hormone levels.

Excess GH is known to cause different disorders, but its long-term impact on internal organs like the liver has remained unclear. To address this, researchers used a mouse model engineered to overproduce bovine GH and examined how chronic hormone exposure affects liver function over time.

“Pathological conditions such as acromegaly or pituitary tumors result in elevated circulating GH levels, which have been implicated in a spectrum of metabolic disorders, potentially by regulating liver metabolism.”

The team found that young mice with GH overexpression showed molecular and cellular patterns similar to those in naturally aged livers. In both groups, genes involved in metabolism were suppressed, while those linked to immune and inflammatory responses were activated. On one hand, the metabolic changes were associated with the buildup of advanced glycation end products, harmful compounds formed when sugars attach to proteins or fats without proper regulation. On the other hand, the immune and inflammatory changes reflected a process known as “inflammaging,” a form of chronic, low-grade inflammation commonly associated with aging. By revealing the overlap between hormone-driven and age-related liver dysfunction, the study provides new insight into how GH may accelerate aging processes.

Importantly, the team showed that reducing glycation stress can reverse many of these negative effects. Mice treated with a compound that lowers glycation levels demonstrated improved liver health, reduced insulin resistance, and enhanced physical function. This intervention also corrected several abnormal genetic patterns caused by excess GH. The findings point to a potential therapeutic strategy for liver diseases associated with aging and hormonal imbalances.

Overall, this research identifies glycation and its byproducts as key contributors to liver damage caused by excess GH. It suggests that targeting glycation could offer broad therapeutic benefits, not only for hormone-related conditions but also for supporting liver health during aging.

DOI - https://doi.org/10.18632/aging.206327

Corresponding authors - Andrzej Bartke - [email protected] and Pankaj Kapahi - [email protected]

Abstract video - https://www.youtube.com/watch?v=6v8xi5muLwA

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Keywords - aging, growth hormone, glycation stress, Gly-Low

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In this episode of the Longevity & Aging Series, Dr. Amparo Santamaria from the Reproductive Hematology Unit at the IVIRMA Alicante Clinic in Spain joins Dr. Evgeniy Galimov to discuss her #research paper #published in Volume 17, Issue 6 of Aging-US, titled “Enhancing oocyte activation in women with ovarian failure: clinical outcomes of the Stem Cell Regenera study using G-CSF mobilization of peripheral blood stem cells and intraovarian injection of stem cell factor-enriched platelet rich plasma in real-world-practice.”

DOI - https://doi.org/10.18632/aging.206274

Corresponding author - Amparo Santamaria - [email protected]

Video interview - https://www.youtube.com/watch?v=Zlezd0x_EJQ

Longevity & Aging Series - www.aging-us.com/longevity

Abstract

The study assesses the effectiveness and safety of the Stem Cell Regenera Treatment for oocyte activation in women with ovarian failure, including conditions such as Poor Ovarian Response (POR), Diminished Ovarian Reserve (DOR), and Premature Ovarian Insufficiency (POI). This retrospective observational study was conducted from January 2023 to December 2024 at the IVIRMA Alicante Clinics in Spain.

Women diagnosed with ovarian failure participated in the study, which involved mobilizing Hematopoietic Stem Cells from bone marrow into peripheral blood using granulocyte colony- stimulating factor (G-CSF). This was followed by an intraovarian injection of Stem Cell Factor- enriched Platelet Rich Plasma (SCFE-PRP).

The primary outcome measures were the rate of oocyte activation, leukocytes and stem cell count, and pregnancy rates. Oocyte activation was defined as an increase in total Antral Follicle Count of three or more follicles after treatment and/or at least a 20% rise in Anti-Müllerian Hormone levels. Safety was assessed based on adverse effects. Pregnancy rates were evaluated for both spontaneous gestation and following in vitro fertilization (IVF) treatment.

A total of 145 women participated: the overall activation rate was 68.28%, with 7.07% achieving spontaneous gestation and 14.14% achieving pregnancy following IVF. Mobilization of CD34+ cells was successful in all participants, with an average collection of 32.96 CD34+ cells/μl. No severe adverse effects were observed. The study concluded that the Stem Cell Regenera Treatment is effective and safe for oocyte activation in women with ovarian failure in real-world practice.

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Keywords - aging, Stem Cell Regenera, oocyte activation, ovarian regeneration, G-CSF, SCFE-PRP, ovarian failure

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BUFFALO, NY — November 13, 2025 — A new #research paper was #published in Volume 17, Issue 10 of Aging-US on October 3, 2025, titled “The role of phenylalanine and tyrosine in longevity: a cohort and Mendelian randomization study.”

In this study led by Jie V. Zhao, Yitang Sun, Junmeng Zhang, and Kaixiong Ye from the University of Hong Kong and the University of Georgia, researchers investigated whether two amino acids, phenylalanine and tyrosine, affect how long people live (lifespan). The results suggest that higher levels of tyrosine are linked to shorter life expectancy in men, pointing to potential sex-specific approaches to promoting longevity.

Phenylalanine and tyrosine are amino acids involved in metabolism and brain function. Both are found in protein-rich foods and dietary supplements, but their long-term effects on aging are not well understood. Tyrosine, in particular, is a building block of neurotransmitters such as dopamine, which regulate mood and cognitive function, making it a molecule of interest in aging research.

The study analyzed data from more than 270,000 individuals in the UK Biobank. Using both observational and genetic methods, the researchers examined the associations between blood levels of phenylalanine and tyrosine with overall mortality and predicted lifespan. Although both amino acids were initially linked to higher mortality risk, only tyrosine showed a consistent and potentially causal association with reduced life expectancy in men. Genetic analyses estimated that elevated tyrosine levels could shorten men’s lifespan by nearly one year. No significant effect was observed in women.

These findings remained consistent even after adjusting for related factors, including the role of phenylalanine. This suggests that tyrosine may independently influence aging. The researchers also observed that men tend to have higher tyrosine levels than women, which could partly explain the gender gap in lifespan.

“Phenylalanine showed no association with lifespan in either men or women after controlling for tyrosine.”

The exact mechanisms behind this effect are still under investigation. However, tyrosine’s involvement in insulin resistance and the production of stress-related neurotransmitters may be contributing factors. Insulin resistance is associated with many age-related diseases, and hormone-related pathways influenced by tyrosine may differ between men and women, potentially explaining the sex-specific outcomes.

Although tyrosine is commonly marketed as a supplement for enhancing focus and mental performance, the study raises concerns about its long-term impact on lifespan. While the researchers did not directly study tyrosine supplementation, their findings suggest that people with high tyrosine levels may benefit from dietary adjustments. Strategies such as protein restriction could help reduce tyrosine levels and support healthier aging.

Further studies are needed to confirm these findings and explore whether diet and lifestyle changes can safely lower tyrosine levels to promote longevity.

DOI - https://doi.org/10.18632/aging.206326

Corresponding author - Jie V. Zhao - [email protected]

Abstract video - https://www.youtube.com/watch?v=rr0G44TD36M

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Aging-US proudly sponsored the Future of Aging Research (FAR) Mixer 2025, hosted by the Aging Initiative on November 7 in Cambridge, MA, uniting students, researchers, and biotechnology leaders to advance aging research and shape a healthier, longer-lived future.

Highlights from the FAR Mixer 2025

The 2025 FAR Mixer featured keynote speaker Dr. Kristen Fortney, Co-Founder and CEO of BioAge Labs, who shared insights into how translational research and clinical pipelines have evolved over the past decade.

Dr. Fortney highlighted how obesity-targeting drugs are opening new avenues for metabolic and aging research. She explained that while obesity and osteoporosis are currently major therapeutic priorities, the next wave of reimbursable diseases will likely focus on muscle loss and chronic inflammation, reflecting their growing recognition as key factors in healthy aging.

She also emphasized the importance of human databases in target discovery, cross-sector partnerships between pharma and biotech, and the increasing focus on small-molecule interventions to address age-related diseases.

Focus talks showcased the diversity and depth of modern aging research.

Full recap - https://aging-us.org/2025/11/aging-us-supports-the-future-of-aging-research-mixer-2025/

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Synucleinopathies are a group of age-related neurological disorders, including Parkinson’s disease, dementia with Lewy bodies, and multiple system atrophy. Most individuals are not diagnosed until these diseases have significantly progressed, as early symptoms, such as a reduced sense of smell, subtle cognitive or motor changes are too vague to serve as reliable indicators.

To uncover specific biological signs that appear earlier and clearly point to the disease process, researchers from Saarland University developed a study titled “Brain region-specific and systemic transcriptomic alterations in a human alpha-synuclein overexpressing rat model,” featured as the cover Aging-US, Volume 17, Issue 10.

Full blog - https://aging-us.org/2025/11/alpha-synuclein-overexpression-in-rats-reveals-early-clues-to-synucleinopathies/

Paper DOI - https://doi.org/10.18632/aging.206331

Corresponding author - Thomas Hentrich - [email protected]

Abstract video - https://www.youtube.com/watch?v=Yl6AfVchkb0

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Keywords - aging, alpha-synuclein, transgenic rat model, different brain regions, transcriptome analysis

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