FOUNTAIN OF YOUTH (LONGEVITY STUDIES)

New drug and enzyme class found to have anti-ageing properties

Researchers from Queen Mary University of London’s School of Biological and Behavioural Sciences, using the simple fission yeast as a model, have shown that new TOR inhibitor rapalink-1 prolongs chronological lifespan.

Queen Mary University of London

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Researchers from Queen Mary University of London’s School of Biological and Behavioural Sciences, using the simple fission yeast as a model, have shown that new TOR inhibitor rapalink-1 prolongs chronological lifespan.  

The new study, published in Communications Biology journal by Juhi Kumar, Kristal Ng and Charalampos Rallis, sheds light on how drugs and natural metabolites can influence lifespan through the Target of Rapamycin (TOR) pathway.  

TOR is a conserved signalling pathway active in humans as well as yeast. It is a central regulator of growth and ageing fundamental in age-related diseases such as cancer and neurodegeneration and is already a major focus of anti-ageing and cancer research, with drugs such as rapamycin showing promise in extending healthy lifespan in animals.  

Rapalink-1, the new drug studied by the team, is a next-generation TOR inhibitor currently under investigation for cancer therapy. The researchers found that rapalink-1 not only slowed aspects of yeast cell growth but also significantly extended lifespan, working through TORC1 — the growth-promoting arm of the TOR pathway. 

Unexpectedly, the study revealed a key role for a set of enzymes called agmatinases, which break down the metabolite agmatine into polyamines. These enzymes act as part of a previously unknown “metabolic feedback loop” that keeps TOR activity in check. When agmatinase function was lost, cells grew faster but aged prematurely — highlighting a trade-off between short-term growth and long-term survival. Supplementing yeast with agmatine or putrescine, the compounds linked to this pathway, also promoted longevity and benefited cells under certain conditions. 

“By showing that agmatinases are essential for healthy ageing, we’ve uncovered a new layer of metabolic control over TOR — one that may be conserved in humans,” said Dr. Rallis. “Because agmatine is produced by diet and gut microbes, this work may help explain how nutrition and the microbiome influence ageing.”  

Rallis acknowledges that agmatine supplements are available in the market, but stresses: “We should be cautious about consuming agmatine for growth or longevity purposes. Our data indicate the agmatine supplementation can be beneficial for growth only when certain metabolic pathways related to arginine breakdown are intact. In addition, agmatine does not always promote beneficial effects as it can contribute to certain pathologies”. 

The findings have broad implications for healthy ageing research, cancer biology, and metabolic disease, pointing to new strategies that combine TOR-targeting drugs with dietary or microbial interventions. 

ENDS 

This press release is based on the paper ‘Rapalink-1 reveals TOR-dependent genes and an agmatinergic axis-based metabolic feedback regulating TOR activity and lifespan in fission yeast’ published in Communications Biology. 

DOI: 10.1038/s42003-025-08731-3 

URL: https://www.nature.com/articles/s42003-025-08731-3 

For more information on this release, to receive a copy of the paper or to speak with Dr Charalampos Rallis, please contact Katy Taylor-Gooby at Queen Mary University of London at k.taylor-gooby@qmul.ac.uk 

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Journal

Communications Biology

DOI

10.1038/s42003-025-08731-3 

Article Title

Rapalink-1 reveals TOR-dependent genes and an agmatinergic axis-based metabolic feedback regulating TOR activity and lifespan in fission yeast

Article Publication Date

29-Sep-2025

 

New study reveals why nature picked today’s proteins

The Hebrew University of Jerusalem

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image: 

Assembly formed by primordial peptides as observed by bright field Microscopy

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Credit: Frenkel-Pinter Lab

Why did life on Earth choose alpha amino acids as the building blocks of proteins? A new study suggests the answer lies in the stability of their inter-molecular interactions. Researchers found that primitive peptide-like molecules made from alpha backbones formed more durable, compartment-like structures than their longer beta counterparts, giving them a potential evolutionary advantage. The findings propose an assembly-driven model for the origins of life, offering fresh insight into how chemistry shaped biology.

A new study from the Hebrew University of Jerusalem sheds light on one of life’s greatest mysteries: why biology is based on a very specific set of amino acids, and in particular, why nature selected alpha amino acids as the foundation for proteins.

The research, led by Dr. Moran Frenkel-Pinter and her lab members Ms. Sarah Fisher and Mr. Yishi Ezerzer of the Institute of Chemistry and the Center for Nanoscience and Nanotechnology at the Hebrew University, explored the properties of depsipeptides—simple model peptide-like molecules that could have formed on the early Earth through natural processes. Unlike modern peptides, depsipeptides contain a mix of ester and amide bonds, making them easier to form under prebiotic conditions but less stable over time.

Every living organism on Earth forms its proteins from the exact same set of 20 amino acids. Why that specific set? The new study suggests that life’s dependence on these 20 amino acids is no accident. A key question has puzzled scientists for decades: why did life favor alpha amino acids over their beta or gamma counterparts, even though all were abundant on the prebiotic Earth? To test whether molecular assembly played a role, Frenkel-Pinter and her team synthesized depsipeptides using a wide range of hydroxy and amino acids, then observed their ability to self-assemble in solution.

The results were striking. Depsipeptides built from alpha acids readily formed stable, droplet-like assemblies that persisted for weeks, even after freezing and thawing. In contrast, beta-based assemblies, if formed, phase-separated more quickly in solution and showed significantly lower physical stability. This difference, the researchers argue, could have been a decisive factor in the evolutionary “choice” of the alpha backbone.

“Self-assembly is one of life’s most fundamental prerequisites,” said Dr. Frenkel-Pinter. “Our findings suggest that the superior ability of alpha-based proto-peptides to form stable compartments may have given them a crucial evolutionary edge, setting the stage for the protein backbones we see in biology today.”

“The question of why evolution handpicked a specific set of amino acids has remained a mystery for a very long time. Taking even a single step toward answering this long-lasting question is remarkable, and it is a privilege to contribute to this pursuit”said Yishi Ezerzer, a master's student co-leading this project together with Sarah Fisher from the Frenkel-Pinter group. "We demonstrate here, for the first time, the ability of depsipeptids to self-assemble, similar to modern peptides. While these findings are a breakthrough in the field of chemical evolution, they may also have future implications for other fields such as the pharmaceutical industry." said Fisher.

The study marks the first time that the assembly properties of alpha and beta proto-peptide backbones have been directly compared. By demonstrating that stability at the molecular level could have influenced chemical evolution, the research proposes an assembly-driven selection model for life’s earliest building blocks.

These findings add a new dimension to origins-of-life studies, suggesting that it was not just chemical reactivity but also the capacity for long-lasting self-assembly that shaped the transition from prebiotic chemistry to biology.

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Journal

Proceedings of the National Academy of Sciences

DOI

10.1073/pnas.2500503122 

Method of Research

Experimental study

Subject of Research

Not applicable

Article Title

Protopeptide backbone affects assembly in aqueous solutions

Article Publication Date

3-Oct-2025

WORD OF THE DAY (WOTD)

Scientists map the navigation styles of wild dogs and cats

Wild canids and felids differ in their reliance on reused travel routeways

FELIX MUST BE SINGULAR

A University of Maryland-led study that followed over 1,200 animals across six continents challenges longstanding assumptions about animal movement and has implications for conservation and management of at-risk mammalian carnivores globally

University of Maryland

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The next time you watch your dog visit the same places around your yard or notice that your cat seems to explore a new area every time it ventures outside, consider this: you might be witnessing an ancient evolutionary strategy in action.

A new study published in the Proceedings of the National Academy of Sciences during the week of September 29, 2025 reveals that wild canids have, on average, both a greater density of travel routeways and a greater probability of routeway usage than wild felids. Led by University of Maryland researchers, the collaborative study used GPS collar data detailing the movements of 1,239 individual carnivores representing 34 species across six continents over the past decade—the largest comparative study of carnivore movement ecology ever conducted.

“We found that carnivore species use space in fundamentally different ways,” said the study’s lead scientist William Fagan, a Distinguished University Professor of Biology at UMD. “Members of the dog family appear much more structured in their uses of space. On average, they rely more heavily on favored travel routes compared to members of the cat family.”

Fagan and his collaborators found that wild members of the dog family—wolves, foxes, coyotes, and others—consistently create and stick to specific travel routes within their territories. But their distant carnivore cousins in the cat family—from bobcats to lions and leopards—tend to roam more freely, relying less strongly on favored routes.

The findings challenge scientists’ traditional understanding of the movement ecology of mammalian predators. Historically, researchers assumed that predators moved randomly throughout their territories, an assumption so widespread that it was baked into standard mathematical models. However, the new findings show that many carnivores create invisible “highway” systems that they use repeatedly to move through portions of their home ranges perhaps thanks in part to the dogs’ powerful sense of smell.

“We suspect that this split reflects deep evolutionary differences in how these species navigate and find their way around,” Fagan explained. “Canids possess superior olfactory abilities compared to felids, potentially helping them establish and remember preferred travel routes. It looks like these different navigation strategies have developed over millions of years since dogs and cats last shared a common ancestor.”

“Given the inherent heterogeneity in such a large, global dataset, the magnitude and consistency of these differences is striking,” says senior author Justin M. Calabrese, head of the Earth System Science research group at CASUS in Germany and Adjunct Professor at UMD. “However, we were careful to check that the lineage-specific differences persisted even after for controlling for many potentially confounding factors.” Intriguingly, the differences between canids and felids actually became stronger when the researchers restricted their analyses to nine shared landscapes where both canids and felids could be studied together, removing the influence of variation in vegetation type, human “footprints”, and other factors across landscapes.

The researchers believe that their findings have many implications for improving wildlife conservation and management practices. Fagan noted that understanding and anticipating regularity of animal movement patterns is crucial for predicting human-wildlife encounters and organizing conservation areas, particularly in protecting endangered species from threats such as poachers. For example, Fagan and collaborators held a workshop at UMD’s Brin Mathematics Research Center focusing on the links between movement, encounters, and the dynamics of disease transmission, mate-finding and predator-prey systems.

“This research was a massive undertaking, beginning as a multitude of email exchanges during the COVID pandemic and ultimately transforming into the world’s biggest comparative carnivore movement dataset involving 177 collaborators around the world. The project demonstrated how modern GPS technology and sophisticated analysis methods developed by our research group can reveal fascinating hidden aspects of animal behavior that were impossible to study just a short time ago,” Fagan said.

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The paper, “Wild canids and felids differ in their reliance on reused travel routeways,” was published in the Proceedings of the National Academy of Sciences during the week of September 29, 2025.

This research was supported by the U.S. National Science Foundation’s Infrastructure Innovation for Biological Research Program (Grant No. 1915347), Germany's Federal Ministry of Education and Research (BMBF) and the Saxon Ministry for Science, Culture, and Tourism (SMWK).

In addition to Fagan, other co-authors of this research affiliated with UMD’s Department of Biology include research technician Ananke G. Krishnan, research scientists Christen H. Fleming and Justin M. Calabrese, PhD students Gayatri Anand, Stephanie Chia, Qianru Liao, and Anshuman Swain, and undergraduates Christina Barrett, Varun Chilukuri, Daisy Liao, Sarah Na, Shreyas Ramulu, Elizabeth Sharkey, and Steven Su. Also contributing were Professor Michael Dougherty from UMD’s Department of Psychology and Assistant Dean Katerina V. Thompson from the College of Computer, Mathematics, and Natural Sciences. 

 

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Journal

Proceedings of the National Academy of Sciences

DOI

10.1073/pnas.2401042122 

Method of Research

Data/statistical analysis

Subject of Research

Animals

Article Title

Wild canids and felids differ in their reliance on reused travel routeways

DECRIMINALIZE DRUGS

Medicaid unwinding associated with less medication treatment for opioid use disorder

Findings may have relevance for upcoming Medicaid cuts

THE STATE OF CRUELTY

RAND Corporation

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The end of pandemic-era enrollment enhancements for Medicaid was associated with a rise in the number of people ending medication treatment for opioid use disorder, as well as a decrease in the number of people beginning such treatment, according to a new RAND study.

 

While some people who disenrolled from Medicaid may have found other methods to pay for drug treatment, the overall number of those initiating and continuing medication treatment for opioid use disorder declined in the six months after Medicaid unwinding began. The changes were greatest in states that have had the largest disenrollments.

 

The study tracked treatment episodes of the opioid use disorder medication buprenorphine from 2021 to 2023 as pandemic-era Medicaid enrollment protections were phased out. The study authors say the findings have relevance given the recent federal legislation expected to result in 10 million Americans losing their Medicaid health coverage by 2034.

 

The study is published in the Journal of Addiction Medicine.

 

“These findings are particularly salient at a time when policy changes are increasing uncertainty about Medicaid coverage for many individuals,” said Bradley D. Stein, the study’s corresponding author and a senior physician policy researcher at RAND, a nonprofit research organization. “To sustain progress the nation has made against the opioid overdose crisis, it is essential to ensure that individuals who can benefit from life-saving medication continue to receive it.”

 

Medication treatment is the most-effective treatment for people battling addiction to fentanyl and other opioids, with buprenorphine being one commonly prescribed treatment for individuals with opioid use disorder. Medicaid covers approximately 40% of treatment for Americans with opioid use disorder.

 

More than 25 million Americans have disenrolled from Medicaid as a result of Medicaid unwinding -- the process in which states resumed normal Medicaid enrollment procedures after a period of continuous coverage mandated during the COVID-19 pandemic.

 

To examine the role that unwinding played in medication treatment for opioid use disorder, RAND researchers examined prescriptions dispensed at retail pharmacies in all 50 states and the District of Columbia to identify buprenorphine treatment episodes from Jan. 1, 2021 to Dec. 31, 2023.

 

About 45% of the buprenorphine treatment episodes were paid for by Medicaid, 18% by commercial insurance, 11% by Medicare, 11% by discount cards/vouchers, and 6% were cash-pay. Approximately 27% of treatment episodes were in high-unwinding states, 41% in moderate-unwinding states, and 31% in low-unwinding states.

 

On average, there were 3% more treatment episodes paid for by Medicaid that ended after unwinding began as compared to before unwinding. In states with the greatest unwinding, the percentage difference was more than double that in states with moderate or low levels of unwinding.

 

There were 2.6% fewer new treatment episodes paid for by Medicaid in the six months after unwinding compared to six months before unwinding. There was a significant 3.9% decrease in new treatment episodes paid for by Medicaid in states with the greatest unwinding, compared to a 2.4% decrease in states with moderate unwinding, and a 2% decrease in states with the smallest amount of unwinding.

 

Changes in treatment episodes paid for by Medicaid appear not to be completely offset by changes in reimbursement from other sources, such as individuals losing Medicaid paying out-of-pocket for buprenorphine or obtaining commercial insurance.

 

“These changes were associated with an increase in the number of Medicaid enrollees stopping buprenorphine treatment and a decrease in enrollees beginning it,” said Rachel K. Landis, study coauthor and policy researcher at RAND. “Consistent with research on total buprenorphine fills, effects were greatest in states with the greatest Medicaid disenrollment.”

 

Research reported in this press release was supported by the National Institute on Drug Abuse of the National Institutes of Health under award number P50DA04635108. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Support for the study was also provided by the Foundation for Opioid Response Efforts (FORE).

Another author of the study is Flora Sheng.

RAND Health Care promotes healthier societies by improving health care systems in the United States and other countries.

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Journal

Journal of Addiction Medicine

DOI

10.1097/ADM.0000000000001573 

Method of Research

Data/statistical analysis

Subject of Research

People

Article Title

Medicaid Unwinding: Association With New and Ending Buprenorphine Treatment Episodes