Message from the oldest-living dogs to dogs and men: Gonad function fights frailty

Gerald P. Murphy Cancer Foundation

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“BORT” (pictured) IS ONE OF THE OLDEST MALE ROTTWEILERS LIVING IN NORTH AMERICA THAT INVESTIGATORS PUT TO WORK TO DISCOVER THE LINKAGE BETWEEN LIFELONG GONAD FUNCTION, LATE-LIFE FRAILTY, AND OVERALL MORTALITY RISK.

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Credit: CENTER FOR EXCEPTIONAL LONGEVITY STUDIES, GERALD P. MURPHY CANCER FOUNDATION

West Lafayette, Ind. – Frailty threatens older individuals because it increases their vulnerability to detrimental health outcomes, such as falling, longer hospitalization, or even shortened life expectancy.  New research exploring the linkage between frailty and mortality risk points to retaining gonad function as a potent strategy to fight late-life frailty.

The study conducted by scientists at the Gerald P. Murphy Cancer Foundation’s Center for Exceptional Longevity Studies was published last week in the peer-reviewed scientific journal Scientific Reports.

The Gerald P. Murphy Cancer Foundation is a not-for-profit research institute focused on cancer and aging.  It is based at the Purdue Research Park of West Lafayette.

To date, research on physical frailty has focused mainly on understanding factors that lead to frailty development to discover strategies that might prevent or postpone frailty.  In contrast, relatively little attention has focused on factors that might influence frailty resilience, so that fewer adverse health consequences take place once frailty occurs.  The results of the new study suggest that the HPG axis — the body’s system of regulating production of the hormone testosterone — can significantly impact the lethality of late-life frailty.

“Our work provides the first description of the relationship between HPG axis integrity and the mortality risk associated with late-life frailty,” said David J. Waters, DVM, PhD, Director of the Murphy Foundation’s Center for Exceptional Longevity Studies.  “Male dogs with the shortest duration of testis exposure had a very high mortality risk associated with late-life frailty, whereas the mortality consequence of increasing frailty was erased in males with the longest gonad exposure.”

The work is important because it directly addresses a critical question: What factors shape the critical aspects of physiology – the critical context – that can reduce the adverse impact of increasing frailty on health outcomes, including mortality?

“On the basis of our findings, we propose that HPG axis function is an important regulator of the impact of late-life frailty,” said Waters, who is also a Faculty Associate in Purdue University’s Center on Aging and the Life Course.

The uniqueness of the study was articulated by Markus H. Schafer, PhD, co-author of the study.  “The research applies a life course approach to determine whether early-life events, such as endocrine hormone disruption, can buffer against late-life challenges,” said Schafer, who is Professor of Sociology at Baylor University, and whose academic work includes describing the buffering role that social connections can exert on the loneliness of people living alone.

“The research results extend current interest in the role that gonadal hormones play in the development of frailty in older men to include a separate, yet complementary consideration — the significant influence gonad function exerts on the adverse consequences of frailty,” Schafer continued.

Cutting edge investigations of frailty and other integrated measures of health demand expertise in multiple disciplines.  “Dr. Waters has assembled an interdisciplinary team with expertise in veterinary medicine, sociology, nutritional science, exercise science, and comparative medicine to confront this knowledge gap,” remarked Kenneth Ferraro, PhD, Distinguished Professor and Founding Director of Purdue’s Center on Aging and the Life Course (CALC).  “Four of the co-authors of this published study working at four different institutions received their Dual-Title PhD from Purdue CALC, the first university in the United States to award a multidisciplinary Dual-Title PhD in Gerontology.”

The work is also notable for opening the door to a new research methodology: Enlisting the oldest-living dogs as our greatest teachers. Waters leads a team conducting the first systematic study of exceptional longevity of companion dogs living in North America.

The Exceptional Aging in Rottweilers Study seeks to better understand highly successful aging and disease resistance through the study of the oldest-living Rottweilers.   From this cohort of dogs who have lived 30% longer than breed average — physiologically equivalent to 100-year-old humans — investigators construct lifetime medical histories using questionnaires, medical records, and phone interviews with dog owners.  “In the new study, we capitalize on this lifetime cohort to test our hypothesis on gonad function fighting frailty by generating a frailty score in geriatric male dogs with a broad range of lifetime testis exposure and then following them from frailty scoring until time of death,” Waters said.

“These exceptional dogs offer a unique opportunity to explore the numerous ways that healthy life span can be extended,” said Waters.

The work in canines has already generated important insights into the linkage between ovaries and longevity and the relationship between early endocrine disruption and risk of cruciate ligament rupture. The new findings extend the investigators’ recently published work on frailty that are challenging conventional thinking about the health consequences associated with spaying or neutering companion dogs.

Waters put the Exceptional Aging in Rottweilers Study in perspective, noting that for centuries dogs have enriched people’s lives in important ways as our pets and our companions.  Now, for the first time, the oldest-living dogs are being investigated with the hope that their extreme natural biology will offer up fresh scientific clues.

To Waters, dogs stepping up to contribute a deeper understanding of what hormones mean to healthy aging makes perfect sense.

“Historically, dogs have played a pivotal role in endocrine hormone research, including the discoveries of insulin and the ability to shrink prostate cancers using androgen ablation,” stated Waters, who is Professor Emeritus, Department of Veterinary Clinical Sciences in Purdue’s College of Veterinary Medicine.  “Our work signals an important step toward better understanding frailty resilience, advancing the prospect that by avoiding HPG axis deterioration we might retain an internal hormonal environment that buffers the adverse impact of frailty.”

Waters points to the growing scientific interest in harnessing the domesticated dog population to pursue these kinds of underexplored research questions.

“We’ve identified a special group of dogs that can help to inform us about the future research directions that will benefit companion dogs and people,” said Waters.  “Our message to these dogs should be a simple one: We’re ready to listen.” 

 

About the Center for Exceptional Longevity Studies

The Center for Exceptional Longevity Studies seeks to identify important genetic, lifestyle, and environmental determinants of healthy longevity and to better understand the complex relationship between aging, cancer, and cancer avoidance.  While the scientific community looks for reliable research approaches to verify exciting scientific leads, we see enormous value in studying pet dogs living with their owners as a virtual aging laboratory. There's a big payoff for validating this kind of innovative thinking — an opportunity to promote healthy longevity in both pets and people. The Gerald P. Murphy Cancer Foundation is a 501 (c)(3) not-for-profit research institute.

About the Purdue University Center on Aging and the Life Course

The Purdue University Center on Aging and the Life Course (CALC) is a university-wide entity created to strengthen interdisciplinary inquiry on aging. The central aims of CALC are to advance research to optimize the aging experience of diverse populations and prepare future leaders in the field of gerontology. Created in 2003 and drawing upon the expertise of faculty associates from more than 20 academic departments, the Center emphasizes the advantage of taking a life course approach to analyze aging and health span from cells to societies.

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Journal

Scientific Reports

DOI

10.1038/s41598-025-20700-8 

Method of Research

Observational study

Subject of Research

Animals

Article Title

Longer duration of intact hypothalamic–pituitary–gonadal (HPG) axis buffers the adverse impact of late-life frailty in male dogs

Article Publication Date

23-Oct-2025

 

The power of geckos: TU Wien solves the puzzle of large molecules

A puzzle in theoretical chemistry has been solved at TU Wien: a new computational method now makes it possible to calculate the forces between large molecules with unprecedented accuracy.

Vienna University of Technology

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Coronene-Dimer: an example for large molecules with Van-der-Waals forces

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Credit: TU Wien

Why can geckos walk up walls? Why does nitrogen become liquid at –196 °C? Many everyday phenomena can be explained by van der Waals forces – weak bonds between molecules that are notoriously difficult to calculate. For years, scientists have struggled with the fact that different computational methods produced conflicting results.

Now, researchers at TU Wien have resolved this discrepancy and found a solution. Ironically, it was the very method long considered the “gold standard” of quantum chemistry that turned out to be the source of the error: it systematically overestimates the energy contained in certain molecular bonds. With an improved variant, the TU Wien team can now correctly predict the behavior of large molecules – an essential step for understanding biological systems and for advancing renewable energy technologies.

A Mystery of Chemistry

“To describe the bonds between large molecules, scientists use different computational approaches,” explain Tobias Schäfer and Andreas Irmler, first authors of the new study. Together with Alejandro Gallo and research group leader Prof. Andreas Grüneis, they compared the most widely used methods.

“One option is to use quantum Monte Carlo simulations,” says Schäfer. “Here, the computer explores countless possible arrangements of electrons – keeping energetically favorable ones and discarding unfavorable ones. Another option is the so-called coupled-cluster approach,” adds Irmler. “In that case, the molecules are treated in their low-energy states, and higher-energy configurations are added later as a kind of correction.”

“This coupled-cluster method has long been regarded as the gold standard,” says Schäfer. “But the closer we looked, the clearer it became that there were small yet persistent deviations compared to the Monte Carlo results – and for years, nobody knew why.”

Now the TU Wien team has found the answer: “We discovered that the coupled-cluster method systematically overestimates binding energies in large, highly polarizable molecules,” explains Irmler. “Our improved variant corrects this deviation without significantly increasing the computational cost.” With this correction, the results now align much more closely with quantum Monte Carlo data.

Large Molecules – Large Importance

This advance is particularly crucial for large molecular systems. “If you want to describe molecules containing up to a hundred atoms, the computational effort becomes enormous,” says Alejandro Gallo. “Even the world’s largest supercomputers reach their limits. To achieve reliable predictions, we need highly sophisticated approximation methods.”

And large molecules are becoming ever more important – in fields ranging from materials research to pharmaceutical development. “If we want to understand how a drug crystallizes inside a tablet, or how strongly a material binds hydrogen for energy storage, we need to model van der Waals forces accurately,” says Schäfer.

From Fundamental Theory to Practical Applications

The new method enables more reliable reference data – not only for traditional simulations but also as training data for AI models. Such models are already being used to design new materials and pharmaceuticals in virtual environments.

“We are building a bridge between ultimate accuracy and practical usability,” says Prof. Andreas Grüneis from the Institute of Theoretical Physics at TU Wien. “This opens up new possibilities for materials science. Our results show that even well-established methods must be continuously re-examined to keep pace with the growing demands of modern research.”

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Journal

Nature Communications

DOI

10.1038/s41467-025-64104-8 

Article Title

Understanding discrepancies in noncovalent interaction energies from wavefunction theories for large molecules

Article Publication Date

24-Oct-2025

Distinct brain features in football players may tell who is at risk of long-term traumatic disease

NYU Langone Health / NYU Grossman School of Medicine

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Brain scans from American football players reveal subtle differences in the brain’s outer grooves when compared to scans from otherwise healthy men who never played contact or collision sports, a new study shows. Its authors say the findings could potentially predict which people are more at risk of chronic traumatic encephalopathy (CTE).

Like many neurodegenerative diseases, CTE is known to worsen over time, and it afflicts many who play contact and collision sports that involve repeated hits to the head. Popular contact sports include soccer and basketball, while common collision sports are football, hockey, and boxing. Despite years of research, clinicians must still rely on autopsies after death to diagnose CTE, often marked by shrinking of the brain and the presence of tau protein deposits in brain grooves (sulci) near blood vessels.

Led by an international team of researchers and NYU Langone Health, the study is part of a long-term effort to develop tests for early detection of CTE. Researchers found that football players had shallower left superior frontal sulci on average than their nonfootball counterparts. Left superior frontal sulci are located on a main groove that runs along the top, front, left side of the brain, which is known from past studies to be physiologically affected in CTE. Researchers say sulci are very small and no more than 1.5 millimeters wide and 15 millimeters deep.

Published online in the journal Brain Communications Sept. 11, the study also showed that football players with increasing years of playing experience had wider left occipitotemporal sulci — a groove that runs along the left side of the brain — than men not involved in contact sports.

The study included an analysis of single MRI brain scans from 169 former college and professional football players. These scans were compared to those from 54 carefully matched males of similar age, weight, and education, who did not play football or similar sports, and who did not have active military backgrounds.

“Our study shows what we believe can be the first structural differences that tell apart brains more at risk of developing chronic traumatic encephalopathy from the brains of people who are less at risk,” said study senior investigator Hector Arciniega, PhD, an assistant professor in the Department of Rehabilitation Medicine at the NYU Grossman School of Medicine. “The work also proves that we can apply what we know about the physical changes observed postmortem in the brains of those with confirmed chronic traumatic encephalopathy to brain scans of living people at increased risk for it.”

Arciniega, who is also a member of NYU Langone’s Concussion Center, says the findings could be adopted as early signs, or biomarkers, for CTE, advancing efforts to develop a diagnostic test, so that future therapies can be applied before the damage becomes irreversible. Because CTE has no cure, identifying and staging the severity of the risk is essential for strategies to prevent and treat the disease. 

It is unclear why differences were detected only on one side of the brain and not in the sulci on both hemispheres, the researchers say. While differences in sulcal brain structure were shown, no differences were observed regarding comparison psychological tests for memory and learning, estimates of the number of head hits and injuries, and for other brain scan measures of tau protein buildup.

The researchers caution that a clinical diagnostic test remains years away. But they note that if future studies validate their findings, additional biomarkers could be combined, as part of many brain features, into a comprehensive CTE risk assessment.

Arciniega says his team has plans to expand its investigations to include more contact and collision sports. He also will test for differences in several other parts of the brain to help identify people most at risk of developing CTE.

Study volunteers were college football players who had at least six years of playing experience and professional football players with at least 12 years of gameplay. Their roles were linemen, receivers, and running and defensive backs. Quarterbacks were excluded because of their relatively low exposure to head trauma.

Funding support for this study was provided by National Institute of Health grants U01NS093334, R01NS100952, K00NS1134919, R21NS140565, and L32MD016519. Additional funding support came from Alzheimer’s Association grant 25AARG-NTF-1377286.

Besides Arciniega, NYU Langone researchers involved in the study are study lead investigator Leonard Jung, MD, and study co-investigators Anya Mirmajlesi, BS, Jared Stearns, BS; Carina Heller, PhD, Brian Im, MD, Shae Datta, MD, and Laura Balcer, MD. Other study co-investigators are Katherine Breedlove, Nicholas Kim, Alana Wickham, Daniel Daneshvar, MD, PhD, Tim Weigand, Tashrif Billah, Ofer Pasternak, PhD, Michael Coleman, Alexander Lin, PhD, and Martha Shenton, PhD, at Harvard Medical School in Boston; Omar John, MD, Zachary Baucom, PhD, Michael Alosco, PhD, and Robert Stern, at Boston University; Yi Su, PhD, Hillary Protas, PhD, and Eric Reiman, MD, at Arizona State University in Phoenix; Charles Adler, MD, PhD, at the Mayo Clinic in Arizona in Scottsdale; Charles Bernick, MD, MPH, at the Cleveland Clinic Lou Ruvo Center for Brain Health in Las Vegas; Jeffrey Cummings, MD, ScD, at the University of Nevada, Las Vegas; Sylvain Bouix, PhD, at the Universite du Quebec in Montreal; and study co-senior investigator Inga Koerte, MD, PhD, at the Ludwig-Maximilians-Universitat Munchen in Germany.

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About NYU Langone Health

NYU Langone Health is a fully integrated health system that consistently achieves the best patient outcomes through a rigorous focus on quality that has resulted in some of the lowest mortality rates in the nation. Vizient Inc. has ranked NYU Langone No. 1 out of 118 comprehensive academic medical centers across the nation for four years in a row, and U.S. News & World Report recently ranked four of its clinical specialties No. 1 in the nation. NYU Langone offers a comprehensive range of medical services with one high standard of care across seven inpatient locations, its Perlmutter Cancer Center, and more than 320 outpatient locations in the New York area and Florida. The system also includes two tuition-free medical schools, in Manhattan and on Long Island, and a vast research enterprise.

Media Contact

David March

212-404-3528

David.March@NYULangone.org

STUDY LINK

https://academic.oup.com/braincomms/article/7/5/fcaf345/8251762?login=true

STUDY DOI

10.1093/braincomms/fcaf345

 

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Journal

Brain Communications

DOI

10.1093/braincomms/fcaf345 

Method of Research

Imaging analysis

Subject of Research

People

Article Title

Sulcal morphology in former American football players

Article Publication Date

11-Sep-2025

COI Statement

Funding support for this study was provided by National Institute of Health grants U01NS093334, R01NS100952, K00NS1134919, R21NS140565, and L32MD016519. Additional funding support came from Alzheimer’s Association grant 25AARG-NTF-1377286.