Scientists found the “holy grail” gene that could one day help humans regrow limbs

Scientists studying axolotls, zebrafish, and mice have uncovered a shared set of genes that could someday help researchers develop therapies for regrowing human limbs. The findings, published in the Proceedings of the National Academy of Sciences, point to a possible new direction for regenerative medicine and gene therapy.

"This significant research brought together three labs, working across three organisms to compare regeneration," said Wake Forest Assistant Professor of Biology Josh Currie, whose lab studies the Mexican axolotl salamander. "It showed us that there are universal, unifying genetic programs that are driving regeneration in very different types of organisms, salamanders, zebrafish and mice."

The project also included Duke University plastic surgeon David A. Brown, who studies digit regeneration in mice, and Kenneth D. Poss of the University of Wisconsin-Madison, whose research focuses on fin regeneration in zebrafish.

Shared Regeneration Genes Across Species

Around the world, more than 1 million amputations occur every year due to diabetes-related vascular disease, traumatic injuries, infections, and cancer, according to Global Burden of Disease statistics. Researchers expect that number to climb as populations age and diabetes becomes more common.

For years, scientists have searched for ways to move beyond prosthetic limbs and toward treatments capable of restoring natural movement, sensation, and function. This new study suggests that a group of genes known as SP genes may play a central role in that effort.

Researchers selected axolotls, zebrafish, and mice because each species offers unique insights into regeneration.

Axolotls are famous for their extraordinary ability to regrow entire limbs along with tails, spinal cord tissue, and parts of organs including the heart, brain, lungs, liver, and jaw.

Zebrafish are another powerful regeneration model because they can repeatedly regrow damaged tail fins. They are also capable of repairing the heart, brain, spinal cord, kidneys, retinas, and pancreas.

Mice were included because, like humans, they are mammals. Mice can regenerate the tips of their digits, and humans can sometimes regrow fingertips if the nailbed remains intact after injury, allowing skin, flesh, and bone to regenerate.

Currie said the team discovered that the regenerating epidermis, or skin tissue, in all three species activated two genes called SP6 and SP8. Researchers then began investigating exactly how those genes contribute to regeneration.

Biology Ph.D. student Tim Curtis Jr. participated in the work in Currie's lab, along with undergraduate Elena Singer-Freeman, a Goldwater Scholar and 2025 Wake Forest graduate in biochemistry and molecular biology.

CRISPR Experiments Reveal Key Limb Regrowth Role

The researchers found that SP8 is especially important for limb regeneration in salamanders. Using CRISPR gene-editing technology, Currie's team removed SP8 from the axolotl genome.

Without the gene, axolotls were unable to properly regenerate limb bones. Scientists observed similar problems in mice when SP6 and SP8 were missing from regenerating digits.

Using those findings, Brown's lab designed a viral gene therapy based on a tissue regeneration enhancer previously identified in zebrafish.

The therapy delivered a signaling molecule called FGF8, which is normally activated by SP8. In mice, the treatment encouraged bone regrowth in damaged digits and partially restored some regenerative abilities lost when the SP genes were absent.

Human limbs cannot naturally regenerate the way salamander limbs do, but researchers believe future therapies could potentially imitate some of the biological mechanisms controlled by SP genes.

"We can use this as a kind of proof of principle that we might be able to deliver therapies to substitute for this regenerative style of epidermis in regrowing tissue in humans," Currie explained.

Building Toward Future Human Limb Regeneration

Researchers caution that the work is still at an early stage, and far more studies will be needed before discoveries in mice could translate into therapies for humans. Even so, Currie described the research as an important foundation for future regenerative treatments.

"Scientists are pursuing many solutions for replacing limbs, including bioengineered scaffolds and stem cell therapies," Currie explained. "The gene-therapy approach in this study is a new avenue that can complement and potentially augment what will surely be a multi-disciplinary solution to one day regenerate human limbs."

Currie also emphasized the importance of collaboration between scientists working on very different animals and biological systems.

"Many times, scientists work in their silos: we're just working in axolotl, or we're just working in mouse, or just working in fish," Currie said. "A real standout feature of this research is that we work across all these different organisms. That is really powerful, and it's something that I hope we'll see more of in the field."

Journal Reference:

1. David A. Brown, Katja K. Koll, Erin Brush, Grant Darner, Timothy Curtis, Thomas Dvergsten, Melissa Tran, Colleen Milligan, David W. Wolfson, Trevor J. Gonzalez, Sydney Jeffs, Alyssa Ehrhardt, Rochelle Bitolas, Madeleine Landau, Kendall Reitz, David S. Salven, Leslie A. Slota-Burtt, Isabel Snee, Elena Singer-Freeman, Sayuri Bhatia, Jianhong Ou, Aravind Asokan, Joshua D. Currie, Kenneth D. Poss. Enhancer-directed gene delivery for digit regeneration based on conserved epidermal factors. Proceedings of the National Academy of Sciences, 2026; 123 (17) DOI: 10.1073/pnas.2532804123

Courtesy:

Wake Forest University. "Scientists found the “holy grail” gene that could one day help humans regrow limbs." ScienceDaily. ScienceDaily, 9 May 2026. <www.sciencedaily.com/releases/2026/05/260508003121.htm>.

 

 

 

 

 

New obesity discovery rewrites decades of fat science

For decades, scientists believed they understood one of the body's key fat-burning proteins. Known as hormone-sensitive lipase, or HSL, the enzyme was thought to work mainly as the body's emergency fuel switch, helping release stored fat when energy runs low.

But researchers uncovered something unexpected. HSL was not just working on the surface of fat droplets inside fat cells. It was also operating deep inside the nucleus of those cells, where DNA is stored and important genetic activity is controlled. The discovery revealed an entirely different side to a protein scientists had studied since the 1960s.

The findings, published in Cell Metabolism, helped solve a long-standing mystery in obesity research and opened new directions for understanding diabetes, heart disease, and other metabolic disorders.

Fat Cells Do Far More Than Store Calories

Fat cells, also called adipocytes, are often viewed as passive storage containers for excess calories. In reality, they are highly active cells that help regulate the body's entire energy system.

Inside adipocytes, fat is stored in structures called lipid droplets. When the body needs fuel between meals or during fasting, hormones such as adrenaline trigger the release of that stored energy. HSL plays a central role in this process by breaking down triglycerides into fatty acids that other organs can use for fuel.

Scientists long assumed that removing HSL would prevent fat breakdown and lead to obesity. Surprisingly, that is not what happened.

Studies in both mice and people with mutations in the HSL gene showed the opposite effect. Instead of accumulating extra fat, they developed lipodystrophy, a rare condition in which the body loses healthy fat tissue.

That contradiction puzzled researchers for years.

Obesity and Dangerous Fat Loss Share Similar Problems

Although obesity and lipodystrophy seem completely different, they can produce many of the same health complications.

In obesity, fat tissue becomes enlarged and dysfunctional. In lipodystrophy, the body lacks enough properly functioning fat tissue. In both cases, adipocytes fail to regulate energy normally, which can contribute to insulin resistance, type 2 diabetes, fatty liver disease, inflammation, and cardiovascular problems.

This overlap suggested that healthy fat tissue is not simply about how much fat the body carries. The quality and function of fat cells may be just as important.

Researchers at the Institute of Cardiovascular and Metabolic Diseases (I2MC) at the University of Toulouse wanted to understand why the loss of HSL caused fat tissue to break down instead of build up. What they found changed the scientific picture of fat metabolism.

Scientists Discover HSL Inside the Cell Nucleus

The research team, led by Dominique Langin, discovered that HSL was located in an unexpected place inside adipocytes: the nucleus.

The nucleus acts as the cell's control center. It contains DNA and regulates which genes are switched on or off. Proteins found in the nucleus often help control cell growth, repair, metabolism, and communication.

"In the nucleus of adipocytes, HSL is able to associate with many other proteins and take part in a program that maintains an optimal amount of adipose tissue and keeps adipocytes 'healthy'," explained Jérémy Dufau, co-author of the study.

Researchers found that nuclear HSL appears to help regulate important cellular systems, including mitochondrial activity and the extracellular matrix, which provides structural support for tissues.

Mitochondria are often called the power plants of cells because they generate energy. The extracellular matrix helps maintain the shape and integrity of tissues. Problems in either system have been linked to obesity, inflammation, and metabolic disease.

A Protein With Two Very Different Jobs

The study showed that HSL behaves differently depending on where it is located inside the cell.

On lipid droplets, HSL acts as an enzyme that helps release stored fat during fasting or exercise. In the nucleus, however, it appears to work more like a regulator that helps maintain healthy adipose tissue.

Researchers also discovered that the amount of HSL inside the nucleus changes in response to the body's metabolic state.

During fasting, adrenaline activates HSL and pushes it out of the nucleus so it can help mobilize fat stores. In obese mice fed a high-fat diet, nuclear HSL levels increased.

The protein's movement appears to be controlled by signaling pathways involving TGF-β and SMAD3, molecules already known to influence inflammation, tissue remodeling, and metabolic disease.

Scientists also found evidence that nuclear HSL interacts with proteins involved in gene expression and RNA processing, suggesting it may directly influence how fat cells function at a genetic level.

Why the Discovery Matters

The findings helped explain why complete HSL deficiency causes lipodystrophy instead of obesity. Without HSL in the nucleus, fat cells may lose their ability to stay healthy and properly maintain adipose tissue.

"HSL has been known since the 1960s as a fat-mobilizing enzyme. But we now know that it also plays an essential role in the nucleus of adipocytes, where it helps maintain healthy adipose tissue," Langin said.

The discovery may also help researchers better understand why some obesity treatments succeed while others fail. Many current therapies focus mainly on reducing fat mass. But the study suggests preserving healthy fat tissue function could be equally important.

Scientists are increasingly recognizing that adipose tissue acts as a complex endocrine organ that communicates with the brain, liver, muscles, and immune system through hormones and signaling molecules. Dysfunctional fat tissue can disrupt the body far beyond weight gain alone.

Obesity Remains a Global Health Challenge

The research arrives as obesity rates continue to rise worldwide. According to global estimates, billions of people are now overweight or obese, increasing the risk of diabetes, heart disease, stroke, sleep apnea, and some cancers.

Researchers hope that understanding how proteins like HSL regulate fat cell health could eventually lead to more targeted therapies for metabolic disease.

Instead of simply trying to eliminate fat, future treatments may focus on restoring the normal function of adipocytes and protecting the biological systems that keep fat tissue healthy in the first place.

Journal Reference:

1. Jérémy Dufau, Emeline Recazens, Laura Bottin, Camille Bergoglio, Aline Mairal, Karima Chaoui, Marie-Adeline Marques, Veronica Jimenez, Miquel García, Tongtong Wang, Henrik Laurell, Jason S. Iacovoni, Remy Flores-Flores, Pierre-Damien Denechaud, Khalil Acheikh Ibn Oumar, Ez-Zoubir Amri, Catherine Postic, Jean-Paul Concordet, Pierre Gourdy, Niklas Mejhert, Mikael Rydén, Odile Burlet-Schiltz, Fatima Bosch, Christian Wolfrum, Etienne Mouisel, Genevieve Tavernier, Dominique Langin. Nuclear hormone-sensitive lipase regulates adipose tissue mass and adipocyte metabolism. Cell Metabolism, 2025; 37 (11): 2250 DOI: 10.1016/j.cmet.2025.09.014

Courtesy:

Université de Toulouse. "New obesity discovery rewrites decades of fat science." ScienceDaily. ScienceDaily, 8 May 2026. <www.sciencedaily.com/releases/2026/05/260508171123.htm>. 

 

 

 

 

Scientists reversed liver aging with young gut bacteria in stunning study

Scientists may have discovered a powerful new link between the gut microbiome, aging, and liver cancer. New research presented at Digestive Disease Week® (DDW) 2026 suggests that restoring gut bacteria to a more youthful state could help protect the liver, reduce age related damage, and potentially lower cancer risk.

The findings come from a mouse study focused on the microbiome, the vast community of bacteria and other microbes living in the digestive system. Researchers found that giving older mice back their own younger gut microbes produced striking effects throughout the body, especially in the liver.

Young Gut Microbiome Protected Aging Mice

To test the idea, scientists collected fecal samples from eight young mice and preserved them for later use. As the mice aged, the researchers transplanted the stored samples back into the same animals through a process known as fecal microbiota transplantation, or FMT.

Another group of eight aging mice served as controls and received sterilized fecal material instead. Researchers also included a small group of young mice to provide baseline comparisons.

By the end of the study, none of the mice that received their restored youthful microbiome developed liver cancer. In contrast, liver cancer appeared in 2 out of 8 untreated aging mice. The treated mice also showed lower levels of inflammation and reduced liver injury.

"We're learning from this work that the aging microbiome actively contributes to liver dysfunction and cancer risk rather than simply reflecting the aging process," said Qingjie Li, PhD, associate professor in the Division of Gastroenterology and Hepatology at The University of Texas Medical Branch, and lead researcher on the study. "The microbiome has a broader influence on the body's cancer defenses than previously understood."

Researchers Found Changes in a Cancer Related Gene

After completing the in vivo study, the research team closely examined liver tissue from the mice. They discovered important differences involving MDM2, a gene already associated with liver cancer development.

Young mice showed low levels of the MDM2 protein, while untreated older mice had much higher levels. Older mice that received the restored microbiome had suppressed MDM2 levels that more closely resembled those seen in younger animals.

"Restoring a more youthful microbiome can reverse several core features of aging at both the molecular and functional level, including inflammation, fibrosis, mitochondrial decline, telomere attrition, and DNA damage," Dr. Li said.

Earlier Heart Research Led to the Discovery

The liver findings emerged unexpectedly from previous research examining the microbiome's effects on heart health. In that earlier cardiac study, scientists observed that altering gut bacteria appeared to improve heart function.

However, when the researchers later analyzed tissue samples, they noticed even stronger effects in the liver. That observation prompted the team to investigate the connection more deeply.

To reduce the chances of immune complications or infection, the researchers used each mouse's own preserved microbiome rather than relying on donor samples. They said this approach also creates a clearer proof of concept for possible future human studies.

Dr. Li stressed that the findings are limited to animal research and cannot yet be applied to people. Still, he said the team hopes to begin first in human clinical trials in the near future.

Courtesy:

Digestive Disease Week. "Scientists reversed liver aging with young gut bacteria in stunning study." ScienceDaily. ScienceDaily, 9 May 2026. <www.sciencedaily.com/releases/2026/05/260509210643.htm>. 

 

 

This simple blood test might detect depression before symptoms appear

 

Blood tests that track how certain white blood cells age may help identify depression by focusing on emotional and cognitive symptoms rather than physical ones.

The research, published in The Journals of Gerontology, Series A: Biological Sciences and Medical Sciences, moves scientists closer to finding a reliable biological marker for depression, a condition that affects nearly one in five adults in the United States.

Blood-Based Clues Could Improve Depression Diagnosis

Today, depression is diagnosed based on what patients report about their symptoms. Doctors may order lab tests to rule out other illnesses, but there is still no objective biological test that can confirm depression or detect it early.

Part of the challenge is that depression does not look the same for everyone. While some people experience physical (or somatic) symptoms such as fatigue, appetite changes, or restlessness, others mainly struggle with emotional and cognitive effects. These can include hopelessness, difficulty thinking clearly, or anhedonia -- the inability to feel pleasure and loss of interest in previously enjoyed activities.

"Depression is not a one-size-fits-all disorder -- it can look really different from person to person, which is why it's so important to consider varied presentations and not just a clinical label," said study author Nicole Beaulieu Perez, assistant professor at NYU Rory Meyers College of Nursing. "Our study reveals unique biological underpinnings of mental health that are often obscured by broad diagnostic categories."

Depression, Immune Health, and HIV

Depression is especially common among people with immune-related conditions such as HIV. This higher risk may stem from a combination of chronic inflammation, social stigma, and economic challenges. Women living with HIV are particularly affected, and depression can interfere with their ability to stay engaged in care and consistently take antiretroviral medications.

"For women with HIV who may be experiencing depression, we want to better understand what's going on and catch it earlier so that it doesn't harm their whole overall health," said Perez.

Studying Biological Aging With Epigenetic Clocks

To better understand the biology behind depression, researchers examined signs of accelerated aging in the body. Biological age, which does not always match a person's chronological age, can be estimated using "epigenetic clocks." These tools measure chemical changes to DNA that occur over time.

The study included 440 women -- 261 living with HIV and 179 without HIV -- from the Women's Interagency HIV Study. Depression symptoms were assessed using the Center for Epidemiologic Studies Depression Scale (CES-D), a 20-item questionnaire that evaluates both somatic and non-somatic symptoms.

Blood samples were also analyzed to measure biological aging using two types of epigenetic clocks. One assessed aging across multiple cell types and tissues, while the other focused specifically on monocytes, a type of white blood cell involved in immune responses. Monocytes play an important role in HIV infection and are often elevated in people with depression.

Aging Immune Cells Linked to Emotional Symptoms

The findings showed that aging in monocytes was strongly associated with non-somatic symptoms of depression. These included anhedonia, feelings of hopelessness, and a sense of failure, in both women with and without HIV.

"This is particularly interesting because people with HIV often have physical symptoms like fatigue that are attributed to their chronic illness rather than a depression diagnosis. But this flips that on its head because we found that these measures are associated with mood and cognitive symptoms, not somatic symptoms," said Perez.

In contrast, the broader epigenetic clock that measured multiple cell types did not show a link to depression symptoms.

Toward Earlier Detection and Personalized Treatment

Perez emphasized that more research is needed before these findings can be used in clinical care. Still, the results point to a future where depression could be detected earlier and more precisely through biological testing.

Such advances could eventually support more personalized treatment approaches, including identifying which medications are most likely to work for a specific individual.

"I think about the adage, 'What gets measured gets managed.' An aspirational goal in mental health would be to combine subjective experience with objective biological testing," said Perez. "Our findings bring us a step closer to this goal of precision mental health care, especially for high-risk populations, by providing a biological framework that could guide future diagnosis and treatment."

Additional study authors include Ke Xu of Yale University; Yanxun Xu, Lang Lang, Gypsyamber D'Souza, and Leah Rubin of Johns Hopkins University; Kathryn Anastos of Albert Einstein College of Medicine; Maria Alcaide of the University of Miami Miller School of Medicine; Mardge Cohen of Stroger Hospital of Cook County Health System; Sadeep Shrestha of the University of Alabama at Birmingham; Andrew Edmonds of UNC Chapel Hill; Jacquelyn Meyers of Downstate Health Sciences University; Seble Kassaye of Georgetown University; Igho Ofotokun of Emory University; and Bradley Aouizerat of NYU.

The research was supported by the National Institute of Mental Health (F32MH129151, P30MH075673) and the National Institute on Minority Health and Health Disparities (K08MD019998).

Journal Reference:

1. Nicole Beaulieu Perez, Ke Xu, Yanxun Xu, Lang Lang, Kathryn Anastos, Maria L Alcaide, Mardge Cohen, Sadeep Shrestha, Andrew Edmonds, Jacquelyn Meyers, Seble Kassaye, Igho Ofotokun, Gypsyamber D’Souza, Bradley Aouizerat, Leah H Rubin. Monocyte Epigenetic Age Acceleration is Linked to Non-Somatic Depressive Symptoms in Women with and Without HIV. The Journals of Gerontology, Series A: Biological Sciences and Medical Sciences, 2026; DOI: 10.1093/gerona/glag083

Courtesy:

New York University. "This simple blood test might detect depression before symptoms appear." ScienceDaily. ScienceDaily, 4 May 2026. <www.sciencedaily.com/releases/2026/05/260504023827.htm>.

 

 

 

 

 

MIT scientists discover millions of “silent synapses” in the adult brain

 

MIT neuroscientists have uncovered a surprising feature of the adult brain. It contains millions of "silent synapses," which are immature connections between neurons that remain inactive until they are needed to help form new memories.

For many years, scientists believed these silent synapses existed only during early development, when the brain is rapidly learning about the world. But the MIT team found that in adult mice, roughly 30 percent of synapses in the brain's cortex are still silent. This suggests the adult brain holds a large reserve of unused connections that can be activated when new information arrives.

Researchers say this hidden pool of synapses may explain how the brain continues to learn throughout life without disrupting existing memories.

"These silent synapses are looking for new connections, and when important new information is presented, connections between the relevant neurons are strengthened. This lets the brain create new memories without overwriting the important memories stored in mature synapses, which are harder to change," says Dimitra Vardalaki, an MIT graduate student and the lead author of the study.

Mark Harnett, an associate professor of brain and cognitive sciences, is the senior author of the paper, published in Nature. Kwanghun Chung, an associate professor of chemical engineering at MIT, is also an author.

Rethinking How Memory Works in the Adult Brain

Silent synapses were first identified decades ago, mostly in young animals. During early development, they are thought to help the brain absorb large amounts of new information about the environment. In mice, scientists believed these synapses disappeared by about 12 days of age (equivalent to the first months of human life).

However, some researchers suspected they might persist into adulthood. Clues came from studies of addiction, which is often considered a form of maladaptive learning. These studies hinted that silent synapses could reappear or remain in the adult brain.

Theoretical work by neuroscientists Stefano Fusi and Larry Abbott also suggested the brain needs a mix of flexible and stable synapses. Some connections must be easy to change to support new learning, while others must remain steady to preserve long-term memories.

A Chance Discovery Using Advanced Imaging

The MIT team was not initially searching for silent synapses. They were following up on earlier work showing that dendrites, the branch-like extensions of neurons, process signals differently depending on their location.

To explore this further, the researchers measured neurotransmitter receptors along dendrites using a technique called eMAP (epitope-preserving Magnified Analysis of the Proteome). This method physically expands brain tissue, allowing scientists to label proteins and view them in extremely high detail.

During this imaging, the researchers noticed something unexpected.

"The first thing we saw, which was super bizarre and we didn't expect, was that there were filopodia everywhere," Harnett says.

Filopodia are tiny protrusions that extend from dendrites. Although they had been observed before, their function was unclear because they are so small and difficult to study with traditional tools.

Filopodia and the Signature of Silent Synapses

Using the eMAP technique, the team found filopodia across multiple regions of the adult mouse brain, including the visual cortex, at levels far higher than previously reported. These structures contained NMDA receptors but lacked AMPA receptors.

This detail is crucial. Active synapses typically have both receptor types, which work together to transmit signals using the neurotransmitter glutamate. NMDA receptors alone cannot pass electrical signals under normal conditions because they are blocked by magnesium ions. Without AMPA receptors, these connections remain electrically inactive, which is why they are called "silent."

Turning Silent Synapses On

To test whether these filopodia function as silent synapses, the researchers used a modified patch clamping technique. This allowed them to measure electrical activity at individual filopodia while simulating the release of glutamate.

They found that glutamate alone did not produce a signal unless the NMDA receptors were experimentally unblocked. This provided strong evidence that these structures behave as silent synapses.

The team then showed it is possible to activate, or "unsilence," these connections. By pairing glutamate release with an electrical signal from the neuron, AMPA receptors accumulated at the synapse. This transformed the silent connection into a fully functional one capable of transmitting signals.

Importantly, this process was much easier than modifying already active synapses.

"If you start with an already functional synapse, that plasticity protocol doesn't work," Harnett says. "The synapses in the adult brain have a much higher threshold, presumably because you want those memories to be pretty resilient. You don't want them constantly being overwritten. Filopodia, on the other hand, can be captured to form new memories."

A Brain That Is Both Flexible and Stable

These findings support the idea that the brain balances flexibility and stability by maintaining a reserve of highly adaptable synapses.

"This paper is, as far as I know, the first real evidence that this is how it actually works in a mammalian brain," Harnett says. "Filopodia allow a memory system to be both flexible and robust. You need flexibility to acquire new information, but you also need stability to retain the important information."

What This Means for Aging and Brain Health

The researchers are now investigating whether similar silent synapses exist in human brains. They also want to understand how these connections change with age or in neurological conditions.

"It's entirely possible that by changing the amount of flexibility you've got in a memory system, it could become much harder to change your behaviors and habits or incorporate new information," Harnett says. "You could also imagine finding some of the molecular players that are involved in filopodia and trying to manipulate some of those things to try to restore flexible memory as we age."

More recent neuroscience research has continued to explore how synaptic plasticity supports lifelong learning. Studies on aging brains suggest that reduced synaptic flexibility may contribute to memory decline, while work in neurodegenerative diseases like Alzheimer's points to disruptions in synapse formation and function. There is also growing interest in targeting synaptic mechanisms to improve cognitive resilience and learning capacity later in life.

Together, these findings paint a picture of the brain as far more dynamic than once believed. Rather than being fixed, it appears to maintain a hidden запас of connections, ready to be activated when new experiences demand it.

The research was funded by the Boehringer Ingelheim Fonds, the National Institutes of Health, the James W. and Patricia T. Poitras Fund at MIT, a Klingenstein-Simons Fellowship, and Vallee Foundation Scholarship, and a McKnight Scholarship.

Journal Reference:

1. Dimitra Vardalaki, Kwanghun Chung, Mark T. Harnett. Filopodia are a structural substrate for silent synapses in adult neocortex. Nature, 2022; 612 (7939): 323 DOI: 10.1038/s41586-022-05483-6

Courtesy:

Massachusetts Institute of Technology. "MIT scientists discover millions of “silent synapses” in the adult brain." ScienceDaily. ScienceDaily, 6 May 2026. <www.sciencedaily.com/releases/2026/05/260504211848.htm>. 

 

 

 

 

 

Your DNA may predict your future success more than your upbringing

A major twin study is shedding new light on the long running debate over nature versus nurture, suggesting that genetics may play a far larger role in future success than many people realize.

Researchers found that IQ measured at age 23 was strongly connected to socioeconomic status by age 27, including education, occupation, and income. According to the study, much of that connection appears to be tied to genetics rather than upbringing alone.

The findings come from the German TwinLife project, a long term research effort designed to examine how genes and environment shape people's lives over time.

Twin Study Explores IQ and Life Outcomes

The research followed about 880 people, including both identical and fraternal twins. Roughly half of the participants were identical twins, who share all of their genes, while the others were fraternal twins, who share about half.

Because the twins were raised in the same households, researchers could compare how much of the differences between them came from genetics versus environment.

The participants took IQ tests at age 23. Four years later, researchers evaluated their socioeconomic status by looking at factors such as education level, occupation, and income.

The results were striking. The researchers estimated that IQ was about 75 percent genetically predicted. They also found that the link between IQ and socioeconomic status was largely explained by genetics, ranging from 69 percent to 98%.

"We knew this before, but this study shows even more clearly that we are driven by our genes and become who we are largely because of them," says personality psychologist Petri Kajonius, whose study was published in Scientific Reports.

Rethinking the "Silver Spoon" Idea

The findings challenge the familiar idea that success mainly comes from growing up in a wealthy or highly educated family.

"The so-called 'silver spoon' isn't as big as you might think. Your home life also depends on your genes," Kajonius explains.

That does not mean family environment has no influence. Instead, the research suggests that inherited traits may shape how people respond to opportunities, education, and life experiences.

The study also raises difficult questions about social mobility and public policy. If genetics strongly influence life outcomes, how much can educational programs and social interventions really change a person's long term trajectory?

 "The study shows that we are born with different genetic predispositions and that it is difficult to bring about long-term change in this regard through policy measures."

What the Findings Mean for Parents and Young Adults

Kajonius says the results may actually offer some reassurance to parents.

Many parents worry that mistakes in raising their children could permanently affect their future success. But the findings suggest parents may have less control over long term socioeconomic outcomes than commonly believed.

That does not mean parenting or educational support are unimportant. Targeted interventions can still help people succeed. However, the research suggests there may be limits to how much external factors can reshape deeply rooted traits over time.

For young adults, the findings may encourage a different perspective on career choices and achievement.

Rather than focusing only on maximizing status or income, Kajonius suggests people may benefit more from pursuing the things they naturally enjoy and excel at.

Important Limitations of the Study

The researchers note several important caveats.

One limitation is that the study did not directly control for parents' IQ or socioeconomic status. Another issue is that studies like this can struggle to fully separate genetics from environment because the two often interact in complex ways.

For example, genetic traits may express themselves differently depending on a person's upbringing or life circumstances. The researchers say this interaction could partly inflate the estimated genetic influence of IQ, potentially by as much as 15 percentage points.

Even with those limitations, the study adds to growing evidence that genetics plays a powerful role in shaping intelligence, opportunity, and life outcomes.

Journal Reference:

1. Petri J. Kajonius. Longitudinal associations between cognitive ability and socioeconomic status are partially genetic in nature. Scientific Reports, 2026; 16 (1) DOI: 10.1038/s41598-026-37786-3

Courtesy:

Lund University. "Your DNA may predict your future success more than your upbringing." ScienceDaily. ScienceDaily, 6 May 2026. <www.sciencedaily.com/releases/2026/05/260505234624.htm>. 

Mysterious RNA led scientists to a hidden layer of cancer

 

The journey began with T3p, a small RNA molecule detected in breast cancer but not in normal tissue. When it was first described in 2018, it stood out as unusual. That initial finding launched a six-year effort to systematically identify similar orphan non-coding RNAs (oncRNAs) across major cancer types, determine which ones actively contribute to disease, and test whether they could help monitor patients using simple blood tests.

In our newly published study, we describe how this work progressed from analyzing large cancer genome datasets to developing machine learning models, conducting large-scale functional experiments in mice, and ultimately confirming the clinical relevance of these RNAs in nearly 200 breast cancer patients using blood samples.

Cancer-Specific OncRNAs Are Widespread

One of the first major discoveries was that this phenomenon was not limited to breast cancer. By examining small RNA sequencing data from The Cancer Genome Atlas across 32 different cancer types, we identified approximately 260,000 cancer-specific small RNAs. We refer to these molecules as oncRNAs, and they were present across every cancer type analyzed.

Their distribution was not random. Each cancer type displayed its own distinct oncRNA expression pattern. Lung cancers, for example, showed a different set of oncRNAs compared with breast cancers. Using these patterns, machine learning models were able to classify cancer types with 90.9% accuracy. When tested in a separate group of 938 tumors, classification accuracy remained high at 82.1%.

Differences also emerged within individual cancers. Basal breast tumors showed oncRNA patterns distinct from luminal tumors, suggesting additional subtypes that may not yet be fully defined. These findings indicate that oncRNAs reflect fundamental aspects of cancer cell state. Patterns of oncRNA presence and absence function as "digital molecular barcodes" that capture cancer identity at multiple levels, including tumor type, subtype, and cellular state.

Some OncRNAs Actively Drive Tumor Growth

Although oncRNAs serve as powerful biomarkers, we also wanted to understand whether some of them directly influence cancer progression. Specifically, we asked whether cancer cells could use these newly emerged RNA molecules to activate oncogenic pathways.

To test this, we created screening libraries containing about 400 oncRNAs from breast, colon, lung, and prostate tumors. These RNAs were introduced into cancer cells using lentiviral vectors. In half of the cases, we increased oncRNA expression. In the other half, we reduced expression using "Tough Decoy" constructs. The modified cells were then implanted into mice to determine which oncRNAs enhanced tumor growth.

Roughly 5% of the oncRNAs produced clear biological effects in xenograft mouse models. Two breast cancer oncRNAs were examined more closely. One triggered epithelial-mesenchymal transition, an essential step in cancer progression and metastasis. The other activated E2F target genes, promoting cell proliferation. Both significantly accelerated tumor growth and increased metastatic colonization in independent cell line models.

When we examined patient tumor data, we found that tumors expressing these same oncRNAs displayed similar pathway changes. Observing consistent biological patterns in TCGA samples and experimental models strengthened our confidence in the findings.

Cancer Cells Release OncRNAs Into the Bloodstream

Perhaps the most clinically important discovery was that cancer cells actively release many of these oncRNAs into the bloodstream. Tracking these circulating RNAs provides insight into how patients are responding to treatment.

We analyzed cell-free RNA from 25 cancer cell lines across 9 tissue types and found that about 30% of oncRNAs are actively secreted. To confirm their clinical relevance, we studied serum samples from 192 breast cancer patients enrolled in the I-SPY 2 neoadjuvant chemotherapy trial. Blood samples were collected before and after treatment, and we calculated the change in total oncRNA burden (ΔoncRNA below).

That single measurement proved highly informative. Patients with high residual oncRNA levels after chemotherapy had nearly 4-fold worse overall survival. This association remained significant even after accounting for standard clinical indicators such as pathologic complete response and residual cancer burden.

This was our most ambitious goal. Although we knew oncRNAs could be detected in blood, it was uncertain whether they would provide meaningful information in real patient samples. Detecting such a strong signal from just 1 milliliter of serum was unexpected.

A New Approach to Monitoring Minimal Residual Disease

These findings address a significant clinical challenge. Monitoring minimal residual disease in breast cancer using markers such as cell-free DNA is difficult because tumors often release very little DNA into the bloodstream, particularly in early stages. RNA-based monitoring may offer an advantage because cancer cells actively secrete RNA rather than passively shedding DNA.

What Comes Next for OncRNA Research

Important biological and clinical questions remain. How do functional oncRNAs exert their effects? Do they interact with proteins or with other RNAs? Could tracking oncRNA changes in real time guide treatment decisions? Might they help detect recurrence earlier or improve patient stratification? Answering these questions will require more extensive research and larger prospective clinical trials.

At the same time, translation is already underway. The discovery that oncRNAs generate cancer-specific signals in blood is moving toward clinical application. We are collaborating with the biotech company Exai Bio (Hani is a co-founder) to develop oncRNA-based diagnostics. The company has been building artificial intelligence models and assembling diverse datasets to improve cancer detection and classification.

Translational research depends on many contributors. When analyzing tens of thousands of samples computationally, it is easy to forget that each one represents a person who volunteered for research, donated blood, and hoped their participation would help others. Honoring those contributions through careful and rigorous science motivates our entire team.

We believe oncRNAs represent a newly recognized class of cancer-emergent molecules that function both as drivers of disease and as biomarkers. By making this resource openly available, we hope to accelerate progress and open new avenues of research in cancer biology.

 

Journal Reference:

1. Jeffrey Wang, Jung Min Suh, Brian J. Woo, Albertas Navickas, Kristle Garcia, Keyi Yin, Lisa Fish, Taylor Cavazos, Benjamin Hänisch, Daniel Markett, Gillian L. Hirst, Lamorna Brown-Swigart, Laura J. Esserman, Laura J. van ‘t Veer, Hani Goodarzi. Systematic annotation of orphan RNAs reveals blood-accessible molecular barcodes of cancer identity and cancer-emergent oncogenic drivers. Cell Reports Medicine, 2026; 102577 DOI: 10.1016/j.xcrm.2025.102577 

Courtesy:

Arc Institute. "Mysterious RNA led scientists to a hidden layer of cancer." ScienceDaily. ScienceDaily, 17 February 2026. <www.sciencedaily.com/releases/2026/02/260216084527.htm>.

 

 

This new blood test could detect cancer before it shows up on scans

 

Scientists have designed a powerful light based sensor capable of detecting extremely small amounts of cancer biomarkers in blood. The innovation could eventually allow doctors to identify early warning signs of cancer and other diseases through a routine blood draw.

Biomarkers such as proteins, fragments of DNA, and other molecules can signal whether cancer is present, how it is progressing, or a person's risk of developing it. The difficulty is that in the earliest stages of disease, these markers exist in extremely low concentrations, making them hard to measure with conventional tools.

"Our sensor combines nanostructures made of DNA with quantum dots and CRISPR gene editing technology to detect faint biomarker signals using a light-based approach known as second harmonic generation (SHG)," said research team leader Han Zhang from Shenzhen University in China. "If successful, this approach could help make disease treatments simpler, potentially improve survival rates and lower overall healthcare costs."

In Optica, Optica Publishing Group's journal for high-impact research, Zhang and his team reported that the device detected lung cancer biomarkers in patient samples at sub-attomolar levels. Even when only a few molecules were present, the system produced a clear and measurable signal. Because the platform is programmable, it could potentially be adapted to identify viruses, bacteria, environmental toxins, or biomarkers linked to conditions such as Alzheimer's disease.

"For early diagnosis, this method holds promise for enabling simple blood screenings for lung cancer before a tumor might be visible on a CT scan," said Zhang. "It could also help advance personalized treatment options by allowing doctors to monitor a patient's biomarker levels daily or weekly to assess drug efficacy, rather than waiting months for imaging results."

Amplification Free Optical Sensing Technology

Most current biomarker tests require chemical amplification to increase tiny molecular signals, which adds time, complexity, and expense. The researchers aimed to create a direct detection strategy that eliminates those additional steps.

The system relies on SHG, a nonlinear optical phenomenon in which incoming light is converted into light with half the wavelength. In this design, SHG takes place on the surface of a two dimensional semiconductor called molybdenum disulfide (MoS₂).

To precisely position the sensing components, the team built DNA tetrahedrons, which are small pyramid shaped nanostructures formed entirely from DNA. These structures hold quantum dots at carefully controlled distances from the MoS₂ surface. The quantum dots intensify the local optical field and boost the SHG signal.

CRISPR-Cas gene editing technology was then incorporated to recognize specific biomarkers. When the Cas12a protein detects its target, it cuts the DNA strands that anchor the quantum dots. This action triggers a measurable drop in the SHG signal. Because SHG produces very little background noise, the system can detect extremely low biomarker concentrations with high sensitivity.

"Instead of viewing DNA only as a biological substance, we use it as programmable building blocks, allowing us to assemble the components of our sensor with nanometer-level precision," said Zhang. "By combining optical nonlinear sensing, which effectively minimizes background noise, with an amplification-free design, our method offers a distinct balance of speed and precision."

Successful Lung Cancer Testing in Human Serum

To evaluate real world performance, the researchers focused on miR-21, a microRNA biomarker associated with lung cancer. After confirming that the device could detect miR-21 in a controlled buffer solution, they tested it using human serum from lung cancer patients to simulate an actual blood test.

"The sensor worked exceptionally well, showing that integrating optics, nanomaterials and biology can be an effective strategy to optimize a device," said Zhang. "The sensor was also highly specific -- ignoring other similar RNA strands and detecting only the lung cancer target."

The next goal is to shrink the optical system. The researchers aim to develop a portable version that could be used at the bedside, in outpatient clinics, or in remote areas with limited medical resources.

Journal Reference:

1. Bowen Du, Xilin Tian, Siyi Han, Yi Liu, Zhi Chen, Yong Liu, Linjun Li, Zheng Xie, Lingfeng Gao, Ke Jiang, Qiao Jiang, Shi Chen, Han Zhang. Sub-attomolar-level biosensing of cancer biomarkers using SHG modulation in DNA-programmable quantum dots/MoS2disordered metasurfaces. Optica, 2026; 13 (2): 319 DOI: 10.1364/OPTICA.577416 

Courtesy:

Optica. "This new blood test could detect cancer before it shows up on scans." ScienceDaily. ScienceDaily, 16 February 2026. <www.sciencedaily.com/releases/2026/02/260216044002.htm>. 

 

 

 

Scientists discover brain switches that clear Alzheimer’s plaques

 

Scientists at Karolinska Institutet in Sweden and the RIKEN Center for Brain Science in Japan have identified two brain receptors that help regulate the breakdown of amyloid beta, the protein that builds up in Alzheimer's disease. Their findings suggest it may be possible to develop future medications that are both safer and more affordable than today's antibody based treatments.

Alzheimer's disease is the leading cause of dementia and is marked by sticky clumps of amyloid beta (Aβ) forming plaques in the brain. Normally, an enzyme called neprilysin helps clear away Aβ. However, neprilysin activity declines with aging and during the progression of the disease. The research team discovered that two somatostatin receptors, SST1 and SST4, work together to control neprilysin levels in the hippocampus, a region essential for memory. The findings were published in the Journal of Alzheimer's Disease.

Boosting the Brain's Natural Defense System

The researchers conducted experiments using genetically modified mice and laboratory grown cells. When both SST1 and SST4 receptors were missing, neprilysin levels dropped. As a result, amyloid beta accumulated and the mice showed memory problems.

The team also tested a compound designed to activate these two receptors. In mice with Alzheimer's-like brain changes, stimulating SST1 and SST4 increased neprilysin levels, reduced amyloid beta buildup, and improved behavior. Importantly, the treatment did not cause serious side effects.

"Our findings show that the brain's own defence against amyloid beta can be strengthened by stimulating these receptors," says Per Nilsson, docent at the Department of Neurobiology, Care Sciences and Society, Karolinska Institutet.

Toward Safer and More Affordable Alzheimer's Drugs

Many of the most advanced Alzheimer's therapies currently rely on antibodies. While these treatments can target amyloid, they are extremely expensive and may trigger significant side effects in some patients.

"If we can instead develop small molecules that pass the blood-brain barrier, our hope is that we will be able to treat the disease at a significantly lower cost and without serious side effects," says Per Nilsson.

SST1 and SST4 belong to a large family of proteins known as G protein-coupled receptors. These receptors are common drug targets because they are well understood and often respond to medications that can be produced at lower cost and taken in pill form.

The project brought together researchers from Karolinska Institutet in Sweden, RIKEN Center for Brain Science in Japan, and several other international universities. Funding was provided by organizations including the Swedish Research Council, the Hållsten Research Foundation, the Alzheimer's Foundation and the private initiative Innovative ways to fight Alzheimer´s disease -- Leif Lundblad Family and others and RIKEN. The researchers report no conflicts of interest.

Journal Reference:

1. Per Nilsson, Karin Sörgjerd, Naomasa Kakiya, Hiroki Sasaguri, Naoto Watamura, Lovisa Johansson, Makoto Shimozawa, Satoshi Tsubuki, Zhulin Zhou, Raul Loera-Valencia, Risa Takamura, Misaki Sekiguchi, Aline Pegel, Stefan Schulz, Takashi Saito, Nobuhisa Iwata, Bengt Winblad, Takaomi C Saido. Somatostatin receptor subtypes 1 and 4 regulate neprilysin, the major amyloid-β degrading enzyme in brain. Journal of Alzheimer’s Disease, 2025; 109 (2): 651 DOI: 10.1177/13872877251392782 

Courtesy:

Karolinska Institutet. "Scientists discover brain switches that clear Alzheimer’s plaques." ScienceDaily. ScienceDaily, 17 February 2026. <www.sciencedaily.com/releases/2026/02/260215225555.htm>. 

 

 

Scientists found a sugar that could defeat deadly superbugs

Researchers in Australia have developed a promising new strategy to combat deadly bacteria that no longer respond to antibiotics. The team engineered antibodies that lock onto a sugar found only on bacterial cells, an approach that could support a new generation of immunotherapies for multidrug resistant infections acquired in hospitals.

The study, published in Nature Chemical Biology, shows that an antibody created in the laboratory was able to eliminate a normally fatal bacterial infection in mice. It works by binding to a distinctive bacterial sugar and alerting the immune system to destroy the invading pathogen.

The project was co led by Professor Richard Payne of the University of Sydney, working with Professor Ethan Goddard Borger at WEHI and Associate Professor Nichollas Scott from the University of Melbourne and the Peter Doherty Institute for Infection and Immunity.

Professor Payne is also set to lead the newly announced Australian Research Council Centre of Excellence for Advanced Peptide and Protein Engineering. This center will build on discoveries like this one to speed the transition from basic research to applications in biotechnology, agriculture, and conservation.

"This study shows what's possible when we combine chemical synthesis with biochemistry, immunology, microbiology and infection biology," Professor Payne said. "By precisely building these bacterial sugars in the lab with synthetic chemistry, we were able to understand their shape at the molecular level and develop antibodies that bind them with high specificity. That opens the door to new ways of treating some devastating drug-resistant bacterial infections."

Why a Bacterial Sugar Is a Unique Target

The antibody developed by the team targets a sugar molecule called pseudaminic acid. Although it resembles sugars found on human cells, this molecule is made only by bacteria. Many dangerous pathogens use it as a key part of their outer surface, helping them survive and evade immune defenses.

Because the human body does not produce this sugar, it offers a highly specific target for developing immunotherapies that avoid harming healthy cells.

Designing a Broad Acting Antibody

To take advantage of this weakness, the researchers first synthesized the bacterial sugar and sugar decorated peptides entirely from scratch. This work allowed them to determine the molecule's exact three dimensional structure and how it appears on bacterial surfaces.

Using this detailed information, the team created what they describe as a "pan-specific" antibody. It can recognize the same sugar across many different bacterial species and strains.

In mouse infection studies, the antibody successfully cleared multidrug resistant Acinetobacter baumannii. This bacterium is a well known cause of hospital acquired pneumonia and bloodstream infections and is especially difficult to treat.

"Multidrug resistant Acinetobacter baumannii is a critical threat faced in modern healthcare facilities across the globe," Professor Goddard-Borger said. "It is not uncommon for infections to resist even last-line antibiotics. Our work serves as a powerful proof-of-concept experiment that opens the door to the development of new life-saving passive immunotherapies."

How Passive Immunotherapy Could Protect Patients

Passive immunotherapy involves giving patients ready made antibodies to quickly control an infection, rather than waiting for the body's adaptive immune system to respond. This approach can be used both to treat active infections and to prevent them.

In hospital settings, it could be used to protect vulnerable patients in intensive care units who are at high risk from drug resistant bacteria.

Associate Professor Scott noted that the antibodies also offer an important new way to study how bacteria cause disease.

"These sugars are central to bacterial virulence, but they've been very hard to study," he said. "Having antibodies that can selectively recognise them lets us map where they appear and how they change across different pathogens. That knowledge feeds directly into better diagnostics and therapies."

Moving Toward Clinical Use

Over the next five years, the team plans to turn these findings into antibody treatments ready for use in the clinic, with a focus on multidrug resistant A. baumannii. Achieving this goal would remove one of the most dangerous members of the ESKAPE pathogens and mark a significant step forward in the global effort to fight antimicrobial resistance.

"This is exactly the kind of breakthrough the new ARC Centre of Excellence is designed to enable," Professor Payne said. "Our goal is to turn fundamental molecular insight into real-world solutions that protect the most vulnerable people in our healthcare system."

The authors declare no competing interests. Funding was received from the National Health and Medical Research Council; Australian Research Council; National Institutes of Health; the Walter and Eliza Hall Institute of Medical Research; Victorian State Government. Researchers acknowledge support of the Melbourne Mass Spectrometry and Proteomics Facility at the Bio21 Molecular Science and Biotechnology Institute.

All animal handling and procedures were conducted in compliance with the University of Melbourne guidelines and approved by the University of Melbourne Animal Ethics Committee (application ID 29017). 

Journal Reference:

1. Arthur H. Tang, Niccolay Madiedo Soler, Kristian I. Karlic, Leo Corcilius, Caitlin E. Clarke-Shepperson, Christopher Lehmann, Aleksandra W. Debowski, Ashleigh L. Dale, Lauren Zavan, Michelle Cielesh, Adedunmola P. Adewale, Karen D. Moulton, Lucy Li, Chenzheng Guan, Christopher McCrory, Maria Kaparakis-Liaskos, Benjamin P. Howden, Norelle L. Sherry, Ruohan Wei, Xuechen Li, Ruth M. Hall, Johanna J. Kenyon, Linda M. Wakim, Francesca L. Short, Danielle H. Dube, Stuart J. Cordwell, Mark Larance, Keith A. Stubbs, Glen P. Carter, Nichollas E. Scott, Ethan D. Goddard-Borger, Richard J. Payne. Uncovering bacterial pseudaminylation with pan-specific antibody tools. Nature Chemical Biology, 2026; DOI: 10.1038/s41589-025-02114-9 

Courtesy: 

University of Sydney. "Scientists found a sugar that could defeat deadly superbugs." ScienceDaily. ScienceDaily, 6 February 2026. <www.sciencedaily.com/releases/2026/02/260206020850.htm>.

 

A hidden brain effect of prenatal alcohol exposure

 

A new study published in JNeurosci reports how experiences before birth may shape the brain and behavior later in life. Led by Mary Schneider and Alexander Converse at the University of Wisconsin-Madison, the interdisciplinary research examined how exposure to alcohol and stress during pregnancy affects rhesus monkey offspring once they reach adulthood.

How Alcohol and Stress Were Studied Before Birth

In the study, pregnant rhesus monkeys were placed into different conditions. Some consumed moderate amounts of alcohol, some were exposed to mild stress, and others experienced both. When the offspring became adults, researchers examined changes in the brain's dopamine system and measured how the animals consumed alcohol.

Both prenatal alcohol exposure and prenatal stress altered the dopamine system in the adult offspring. Monkeys exposed to alcohol before birth also drank alcohol more quickly as adults. Notably, measurements of the dopamine system taken before the animals had any alcohol were able to predict their later drinking behavior. These findings align with evidence from human studies of alcohol use disorder and suggest that certain brain differences may be present even before problematic drinking begins.

Brain Changes That Continue With Drinking

As the adult offspring consumed alcohol, researchers observed additional changes in the dopamine system. These changes influenced how much alcohol each individual drank and differed from one animal to another. The research team suggests that these individualized brain responses to alcohol may help drive the shift from typical drinking patterns to alcohol use disorder in some individuals.

Implications for Pregnancy and Human Health

According to the researchers, the findings reinforce the message that drinking during pregnancy is not advisable, linking prenatal alcohol exposure to unhealthy drinking patterns later in life. While the study did not find a direct association between prenatal stress and adult drinking behavior, the authors note that prenatal stress may still affect other behaviors not examined in this work.

The researchers also emphasize that their experimental design closely reflects how prenatal alcohol exposure and stress occur in humans. This strengthens the clinical relevance of the findings and helps bridge the gap between animal research and human health outcomes

Journal Reference:

1. Alexander K. Converse, Elizabeth O. Ahlers, Todd E. Barnhart, Bradley T. Christian, Onofre T. DeJesus, Jonathan W. Engle, James E. Holden, Julie A. Larson, Jeffrey M. Moirano, Dhanabalan Murali, Robert J. Nickles, Leslie M. Resch, Colleen F. Moore, Mary L. Schneider. Prenatal Stress and Prenatal Alcohol Alter the Adult Dopamine System and Alcohol Consumption: Dopamine Drives Drinking Behavior in a Prospective Twenty-Year Longitudinal Experiment with Rhesus Macaques. The Journal of Neuroscience, 2026; e0717252026 DOI: 10.1523/JNEUROSCI.0717-25.2026 

Courtesy:

Society for Neuroscience. "A hidden brain effect of prenatal alcohol exposure." ScienceDaily. ScienceDaily, 6 February 2026. <www.sciencedaily.com/releases/2026/02/260206020852.htm>. 

 

 

Menopause linked to grey matter loss in key brain regions

 

New findings from the University of Cambridge suggest that menopause is associated with changes in brain structure, along with higher levels of anxiety, depression, and sleep difficulties. Researchers found reduced grey matter volume in several important brain regions among women who had gone through menopause.

The study, published in Psychological Medicine, also examined the effects of hormone replacement therapy (HRT). While HRT did not appear to prevent these brain or mental health changes, it was associated with a slower decline in reaction speed.

Understanding Menopause and Its Symptoms

Menopause marks the stage of life when a woman's menstrual periods permanently stop due to declining hormone levels. It most commonly occurs between ages 45 and 55 and is often accompanied by symptoms such as hot flushes, low mood, and disrupted sleep. Previous research has also linked menopause to changes in cognitive abilities, including memory, attention, and language.

To help manage menopause related symptoms, particularly depression and sleep problems, many women are prescribed HRT. In England, 15% of women were prescribed HRT in 2023. Despite its widespread use, scientists still have limited insight into how menopause and HRT affect the brain, thinking skills, and mental health.

A Large Study Using UK Biobank Data

To better understand these effects, researchers analyzed data from the UK Biobank involving nearly 125,000 women. Participants were divided into three groups: women who had not yet reached menopause, women who were post-menopause and had never used HRT, and women who were post-menopause and had used HRT.

Participants completed questionnaires about menopause symptoms, mental health, sleep patterns, and overall health. Some also completed cognitive tests measuring memory and reaction time. In addition, around 11,000 women underwent magnetic resonance imaging (MRI) scans, which allowed researchers to examine differences in brain structure.

The average age at menopause among participants was about 49.5 years. Women who were prescribed HRT typically began treatment at around age 49.

Anxiety Depression and Sleep After Menopause

Women who had gone through menopause were more likely than those who had not to seek help from a GP or psychiatrist for anxiety, nervousness, or depression. They also scored higher on depression questionnaires and were more likely to have been prescribed antidepressant medications.

Women in the HRT group showed higher levels of anxiety and depression compared with women who did not use HRT. However, further analysis revealed that these differences were already present before menopause began. According to the researchers, this suggests that some GPs may have prescribed HRT in anticipation that menopause could worsen existing symptoms.

Sleep problems were also more common after menopause. Post-menopausal women were more likely to report insomnia, reduced sleep, and ongoing tiredness. Women using HRT reported feeling the most fatigued of all three groups, even though their total sleep duration did not differ from post-menopausal women who were not taking HRT.

The Importance of Lifestyle and Mental Health Support

Dr. Christelle Langley from the Department of Psychiatry said: "Most women will go through menopause, and it can be a life-changing event, whether they take HRT or not. A healthy lifestyle -- exercising, keeping active and eating a healthy diet, for example -- is particularly important during this period to help mitigate some of its effects.

"We all need to be more sensitive to not only the physical, but also the mental health of women during menopause, however, and recognize when they are struggling. There should be no embarrassment in letting others know what you're going through and asking for help."

Reaction Time Slows While Memory Remains Stable

Menopause was also linked to changes in cognitive performance. Women who were post-menopause and not using HRT showed slower reaction times compared with women who had not yet reached menopause and those who were using HRT. Memory performance did not differ significantly among the three groups.

Dr. Katharina Zühlsdorff from the Department of Psychology at the University of Cambridge, said: "As we age, our reaction times tend to get slower -- it's just a part of the natural ageing process and it happens to both women and men. You can imagine being asked a question at a quiz -- while you might still arrive at the correct answer as your younger self, younger people would no doubt get there much faster. Menopause seems to accelerate this process, but HRT appears to put the brakes on, slowing the ageing process slightly."

 Journal Reference:

1. Katharina Zuhlsdorff, Christelle Langley, Richard Bethlehem, Varun Warrier, Rafael Romero Garcia, Barbara J Sahakian. Emotional and cognitive effects of menopause and hormone replacement therapy. Psychological Medicine, 2026; 56 DOI: 10.1017/S0033291725102845 

Courtesy:

 University of Cambridge. "Menopause linked to grey matter loss in key brain regions." ScienceDaily. ScienceDaily, 7 February 2026. <www.sciencedaily.com/releases/2026/02/260207092904.htm>. 

 

One protein may decide whether brain chemistry heals or harms

Tryptophan is widely known for its connection to sleep, but its importance goes much further. The compounds produced from tryptophan help build proteins, generate cellular energy (NAD+), and create essential brain chemicals such as serotonin and melatonin. Together, these processes support mood, learning, and healthy sleep patterns.

As the brain ages or develops neurological disease, this system begins to break down. Scientists have repeatedly observed disruptions in how tryptophan is processed in aging brains, with even stronger effects seen in neurodegenerative and psychiatric disorders. These changes are linked to worsening mood, impaired learning, and disturbed sleep. Until now, however, researchers did not know what caused the brain to shift how it uses tryptophan in the first place.

SIRT6 Identified as a Key Regulator of Brain Chemistry

Prof. Debra Toiber and her research team at Ben-Gurion University of the Negev have now uncovered a clear biological explanation. Their work points to the loss of a longevity-related protein called Sirtuin 6 (SIRT6) as the driving factor behind this metabolic imbalance.

Using experiments in cells, Drosophila (fly), and mouse models, the researchers showed that SIRT6 plays an active role in controlling gene expression (e.g., TDO2, AANAT). When SIRT6 levels drop, this control is lost. As a result, tryptophan is redirected toward the kynurenic pathway, which produces neurotoxic compounds, while the production of protective neurotransmitters such as serotonin and melatonin declines.

Published Evidence and a Reversible Effect

The findings were recently published in Nature Communications.

Importantly, the researchers also found that the damage caused by this shift is not permanent. In a SIRT6 knockout fly model, blocking the enzyme TDO2 led to a significant improvement in movement problems and reduced the formation of vacuoles, which are signs of brain tissue damage. These results suggest that there may be a meaningful window for therapeutic intervention.

"Our research positions SIRT6 as a critical, upstream drug target for combating neurodegenerative pathology," says Prof. Toiber.

Research Team and Funding Support

Additional researchers include: Shai Kaluski-Kopatch, Daniel Stein, Alfredo Garcia Venzor, Ana Margarida Ferreira Campos, Melanie Planque, Bareket Goldstein, Estefanía De Allende-Becerra, Dmitrii Smirnov, Adam Zaretsky, Dr Ekaterina Eremenko -- Sgibnev, Miguel Portillo, Monica Einav, Alena Bruce Krejci, Uri Abdu, Ekaterina Khrameeva, Daniel Gitler, and Sarah-Maria Fendt.

The study was supported by the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (grant agreement No 849029), the David and Inez Myers foundation, the Israeli Ministry of Science and Technology (MOST), the High-tech, Bio-tech and Negev fellowships of Kreitman School of Advanced Research of Ben-Gurion University and The Israel Science Foundation (Grant no. 422/23). The RNA-seq data analysis was supported by the Russian Science Foundation (grant number 25-71-20017). 

 

Journal Reference:

1. Shai Kaluski-Kopatch, Daniel Stein, Alfredo Garcia Venzor, Ana Margarida Ferreira Campos, Melanie Planque, Bareket Goldstein, Estefanía De Allende-Becerra, Dmitrii Smirnov, Adam Zaretsky, Ekaterina Eremenko, Miguel Portillo, Monica Einav, Alena Bruce Krejci, Uri Abdu, Ekaterina Khrameeva, Daniel Gitler, Sarah-Maria Fendt, Debra Toiber. Histone deacetylase SIRT6 regulates tryptophan catabolism and prevents metabolite imbalance associated with neurodegeneration. Nature Communications, 2025; 17 (1) DOI: 10.1038/s41467-025-67021-y 

Courtesy:

Ben-Gurion University of the Negev. "One protein may decide whether brain chemistry heals or harms." ScienceDaily. ScienceDaily, 15 January 2026. <www.sciencedaily.com/releases/2026/01/260115022811.htm>. 

Statins may help almost everyone with type 2 diabetes live longer

 

A large long-term study has found that statins, a widely used class of cholesterol-lowering medications, significantly reduce the risk of death and serious heart-related problems in adults with type 2 diabetes. Importantly, these benefits were seen even in people who were considered to have a low chance of developing heart disease within the next 10 years. This challenges a long-standing debate over whether preventive statin treatment is worthwhile for patients who appear to be at lower cardiovascular risk.

Statins are commonly prescribed to lower LDL cholesterol, what many people know as bad cholesterol. High LDL levels are linked to clogged arteries, heart attacks, and strokes. People with type 2 diabetes already face a higher risk of cardiovascular disease, but doctors have not always agreed on whether statins are necessary for those whose short-term heart risk appears minimal. The new findings suggest that statins may offer protective effects for a much wider group of diabetes patients than previously believed. The study was published in Annals of Internal Medicine.

The research team, led by scientists from the University of Hong Kong, examined health records from the IQVIA Medical Research Data (IMRD)-UK database. Their goal was to assess both the effectiveness and safety of starting statin therapy for primary prevention. Primary prevention refers to preventing a first heart attack or stroke before any such event has occurred.

The study focused on adults in the United Kingdom with type 2 diabetes between the ages of 25 and 84. Participants were followed for as long as 10 years. At the start of the study, none of the individuals had serious heart disease or significant liver problems, allowing researchers to more clearly assess the effects of statins without interference from existing severe conditions.

Statins Reduced Death and Heart Events at Every Risk Level

Researchers compared people who began taking statins with those who did not, grouping them based on their predicted 10-year risk of developing cardiovascular disease. This risk estimate is commonly used in clinical practice to guide treatment decisions.

Across all risk categories, statin use was linked to lower rates of death from any cause and fewer major cardiovascular events such as heart attacks and strokes. Even participants classified as low risk experienced measurable benefits, which directly challenges the assumption that statins only help people already at high risk of heart disease.

Safety Findings and What They Mean for Patients

In terms of safety, the researchers observed a very small increase in myopathy in one risk group. Myopathy refers to muscle-related side effects, which can include weakness or soreness and are a known but uncommon concern with statin use. No increase in liver-related problems was found, addressing another common worry among patients and clinicians.

Based on these results, the authors concluded that doctors should carefully consider the advantages of statin therapy for all adults with type 2 diabetes, even when a person's short-term predicted risk of cardiovascular disease is low. The findings suggest that relying solely on short-term risk estimates may cause some patients to miss out on treatments that could help them live longer and avoid serious heart complications.

Journal Reference:

1. Vincent Ka Chun Yan, Joseph Edgar Blais, John-Michael Gamble, Esther Wai Yin Chan, Ian Chi Kei Wong, Eric Yuk Fai Wan. Effectiveness and Safety of Statins in Type 2 Diabetes According to Baseline Cardiovascular Risk. Annals of Internal Medicine, 2025; DOI: 10.7326/ANNALS-25-00662 

Courtesy:

American College of Physicians. "Statins may help almost everyone with type 2 diabetes live longer." ScienceDaily. ScienceDaily, 15 January 2026. <www.sciencedaily.com/releases/2026/01/260115022812.htm>. 

 

 

Scientists reverse Alzheimer’s in mice and restore memory

 

A study reveals that restoring the brain's energy balance may not just slow Alzheimer's -- but actually reverse it.

• For more than a century, Alzheimer's disease has been widely viewed as permanent and untreatable once it begins. As a result, most research has focused on preventing the disease or slowing its progression rather than attempting to reverse it.
• By studying multiple mouse models of Alzheimer's alongside human Alzheimer's brain tissue, researchers identified a critical biological problem at the center of the disease. They found that the brain's inability to maintain healthy levels of a vital cellular energy molecule called NAD+ plays a major role in driving Alzheimer's.
• In animal models, maintaining normal brain NAD+ levels prevented Alzheimer's from developing. Even more striking, restoring NAD+ balance after the disease was already advanced allowed the brain to repair damage and fully restore cognitive function.
• These results suggest that treatments aimed at restoring the brain's energy balance could potentially move Alzheimer's therapy beyond slowing decline and toward meaningful recovery.
• The findings also open the door to further research, including the exploration of complementary strategies and carefully designed clinical trials to determine whether these results can translate to patients.

A Longstanding View of Alzheimer's Is Being Questioned

For more than 100 years, Alzheimer's disease (AD) has been widely viewed as a condition that cannot be undone. Because of this belief, most scientific efforts have focused on preventing the disease or slowing its progression, rather than attempting to restore lost brain function. Even after decades of research and billions of dollars in investment, no drug trial for Alzheimer's has ever been designed with the goal of reversing the disease and recovering cognitive abilities.

That long-held assumption is now being challenged by researchers from University Hospitals, Case Western Reserve University, and the Louis Stokes Cleveland VA Medical Center. Their work set out to answer a bold question: can brains already damaged by advanced Alzheimer's recover?

New Study Targets Brain Energy Failure

The research was led by Kalyani Chaubey, PhD, of the Pieper Laboratory and published on December 22 in Cell Reports Medicine. By examining both human Alzheimer's brain tissue and multiple preclinical mouse models, the team identified a key biological failure at the center of the disease. They found that the brain's inability to maintain normal levels of a critical cellular energy molecule called NAD+ plays a major role in driving Alzheimer's. Importantly, maintaining proper NAD+ balance was shown to not only prevent the disease but also reverse it in experimental models.

NAD+ levels naturally decline throughout the body, including the brain, as people age. When NAD+ drops too low, cells lose the ability to carry out essential processes needed for normal function and survival. The researchers discovered that this decline is far more severe in the brains of people with Alzheimer's. The same pattern was seen in mouse models of the disease.

How Alzheimer's Was Modeled in the Lab

Although Alzheimer's occurs only in humans, scientists study it using specially engineered mice that carry genetic mutations known to cause the disease in people. In this study, researchers used two such models. One group of mice carried multiple human mutations affecting amyloid processing, while the other carried a human mutation in the tau protein.

Amyloid and tau abnormalities are among the earliest and most significant features of Alzheimer's. In both mouse models, these mutations led to widespread brain damage that closely mirrors the human disease. This included breakdown of the blood-brain barrier, damage to nerve fibers, chronic inflammation, reduced formation of new neurons in the hippocampus, weakened communication between brain cells, and extensive oxidative damage. The mice also developed severe memory and cognitive problems similar to those seen in people with Alzheimer's.

Testing Whether Alzheimer's Damage Could Be Reversed

After confirming that NAD+ levels dropped sharply in both human and mouse Alzheimer's brains, the team explored two possibilities. They tested whether maintaining NAD+ balance before symptoms appeared could prevent Alzheimer's, and whether restoring that balance after the disease had already progressed could reverse it.

This approach built on the group's earlier work published in Proceeding of the National Academy of Sciences USA, which showed that restoring NAD+ balance led to both structural and functional recovery after severe, long-lasting traumatic brain injury. In the current study, the researchers used a well-characterized pharmacologic compound called P7C3-A20, developed in the Pieper laboratory, to restore NAD+ balance.

Full Cognitive Recovery Observed in Advanced Disease

The results were striking. Preserving NAD+ balance protected mice from developing Alzheimer's, but even more surprising was what happened when treatment began after the disease was already advanced. In those cases, restoring NAD+ balance allowed the brain to repair the major pathological damage caused by the genetic mutations.

Both mouse models showed complete recovery of cognitive function. This recovery was also reflected in blood tests, which showed normalized levels of phosphorylated tau 217, a recently approved clinical biomarker used to diagnose Alzheimer's in people. These findings provided strong evidence of disease reversal and highlighted a potential biomarker for future human trials.

Researchers Express Cautious Optimism

"We were very excited and encouraged by our results," said Andrew A. Pieper, MD, PhD, senior author of the study and Director of the Brain Health Medicines Center, Harrington Discovery Institute at UH. "Restoring the brain's energy balance achieved pathological and functional recovery in both lines of mice with advanced Alzheimer's. Seeing this effect in two very different animal models, each driven by different genetic causes, strengthens the idea that restoring the brain's NAD+ balance might help patients recover from Alzheimer's."

Dr. Pieper also holds the Morley-Mather Chair in Neuropsychiatry at UH and the CWRU Rebecca E. Barchas, MD, DLFAPA, University Professorship in Translational Psychiatry. He serves as Psychiatrist and Investigator in the Louis Stokes VA Geriatric Research Education and Clinical Center (GRECC).

A Shift in How Alzheimer's Is Viewed

The findings suggest a fundamental change in how Alzheimer's could be approached in the future. "The key takeaway is a message of hope -- the effects of Alzheimer's disease may not be inevitably permanent," said Dr. Pieper. "The damaged brain can, under some conditions, repair itself and regain function."

Dr. Chaubey added, "Through our study, we demonstrated one drug-based way to accomplish this in animal models, and also identified candidate proteins in the human AD brain that may relate to the ability to reverse AD."

Why This Approach Differs From Supplements

Dr. Pieper cautioned against confusing this strategy with over the counter NAD+-precursors. He noted that such supplements have been shown in animal studies to raise NAD+ to dangerously high levels that promote cancer The method used in this research relies instead on P7C3-A20, a pharmacologic agent that helps cells maintain healthy NAD+ balance during extreme stress, without pushing levels beyond their normal range.

"This is important when considering patient care, and clinicians should consider the possibility that therapeutic strategies aimed at restoring brain energy balance might offer a path to disease recovery," said Dr. Pieper.

Next Steps Toward Human Trials

The research also opens the door to additional studies and eventual testing in people. The technology is currently being commercialized by Glengary Brain Health, a Cleveland-based company co-founded by Dr. Pieper.

"This new therapeutic approach to recovery needs to be moved into carefully designed human clinical trials to determine whether the efficacy seen in animal models translates to human patients," Dr. Pieper explained. "Additional next steps for the laboratory research include pinpointing which aspects of brain energy balance are most important for recovery, identifying and evaluating complementary approaches to Alzheimer's reversal, and investigating whether this recovery approach is also effective in other forms of chronic, age-related neurodegenerative disease."

Journal Reference:

1. Kalyani Chaubey, Edwin Vázquez-Rosa, Sunil Jamuna Tripathi, Min-Kyoo Shin, Youngmin Yu, Matasha Dhar, Suwarna Chakraborty, Mai Yamakawa, Xinming Wang, Preethy S. Sridharan, Emiko Miller, Zea Bud, Sofia G. Corella, Sarah Barker, Salvatore G. Caradonna, Yeojung Koh, Kathryn Franke, Coral J. Cintrón-Pérez, Sophia Rose, Hua Fang, Adrian A. Cintrón-Pérez, Taylor Tomco, Xiongwei Zhu, Hisashi Fujioka, Tamar Gefen, Margaret E. Flanagan, Noelle S. Williams, Brigid M. Wilson, Lawrence Chen, Lijun Dou, Feixiong Cheng, Jessica E. Rexach, Jung-A Woo, David E. Kang, Bindu D. Paul, Andrew A. Pieper. Pharmacologic reversal of advanced Alzheimer’s disease in mice and identification of potential therapeutic nodes in human brain. Cell Reports Medicine, 2025; 102535 DOI: 10.1016/j.xcrm.2025.102535 

Courtesy:

University Hospitals Cleveland Medical Center. "Scientists reverse Alzheimer’s in mice and restore memory." ScienceDaily. ScienceDaily, 24 December 2025. <www.sciencedaily.com/releases/2025/12/251224032354.htm>.