The protein, known as Miro1, was found at higher levels in the skeletal muscles of people with Type 2 diabetes. In preclinical experiments, scientists discovered that removing Miro1 restored the muscles’ response to insulin. They also found that exercise lowered Miro1 levels in people with the disease, offering new insight into how physical activity improves insulin sensitivity.

The findings were published in Nature Communications and could help researchers better understand the biological processes behind insulin resistance, a central feature of Type 2 diabetes.

How a Hidden Muscle Protein Affects Insulin Resistance

Miro1 (Mitochondrial Rho GTPase1) is located on the outer membrane of mitochondria, the tiny structures inside cells responsible for producing energy. Researchers believe that excessive amounts of this protein may interfere with how muscles respond to insulin, making it more difficult for the body to regulate blood sugar effectively.

To investigate this connection, the research team studied Miro1 in laboratory cells, preclinical models, and people living with Type 2 diabetes. By examining the protein across these different settings, they were able to explore its effects on muscle function and determine whether the findings could be relevant to human disease.

The results showed that Miro1 buildup impaired the muscles’ response to insulin. When researchers removed the protein in preclinical models, insulin responsiveness returned, providing evidence that Miro1 contributes directly to this process.

Exercise Reduces a Protein Linked to Type 2 Diabetes

The researchers also investigated whether exercise could influence Miro1 levels in people with diabetes. In a randomized controlled trial involving participants with obesity and Type 2 diabetes, they compared the effects of aerobic exercise with those of standard medical care.

People assigned to the exercise group experienced a decline in Miro1 levels in their muscles. These changes occurred alongside improvements in insulin sensitivity and the muscles’ capacity to produce energy.

The findings suggest that reducing Miro1 may be one of the ways exercise helps the body respond more effectively to insulin. They also raise the possibility that treatments designed to target the protein could eventually provide additional benefits alongside physical activity.

“Insulin resistance in muscle is at the heart of Type 2 diabetes, and its molecular causes have remained frustratingly unclear. This study, the product of years of work, identifies Miro1 as a key part of the answer. By tracing Miro1 from cells to preclinical models to patients, we show that Miro1 accumulation impairs the muscle’s response to insulin, that removing it causally restores that response in our models, and that exercise reverses its buildup in people. For the field, this is a new therapeutic target. For patients, it deepens our understanding of why exercise is so effective and opens a path toward treatments that could one day complement it,” said Dr. John P. Kirwan, the study’s senior author.

A Promising New Direction for Diabetes Treatment

Kirwan recently became executive director of the OU Health Harold Hamm Diabetes Center at the University of Oklahoma. He carried out the research while working at LSU’s Pennington Biomedical Research Center and has since brought his internationally recognized translational research program to the University of Oklahoma.

He also serves as Vice Provost for Diabetes Programs at the university and holds the Chickasaw Nation Endowed Chair in Diabetes Research.

The study’s first author, Elizabeth Heintz, is a doctoral candidate who worked in the Integrated Physiology and Molecular Medicine Laboratory at Pennington Biomedical. Christopher Axelrod, the study’s co-corresponding author, has also moved to the Harold Hamm Diabetes Center, joining Kirwan in continuing this line of research.

Dr. Jennifer Rood, Interim Senior Vice Chancellor and Executive Director of Pennington Biomedical, emphasized the importance of connecting laboratory discoveries with research involving patients and broader populations.

“This research exemplifies the breadth of scientific discovery at Pennington Biomedical, where research spans all levels, from basic science that reveals the biological mechanisms underlying disease to clinical studies and population-based research that informs public health,” said Dr. Jennifer Rood, Interim Senior Vice Chancellor and Executive Director of Pennington Biomedical. “Dr. Kirwan and his team’s findings on Miro1 demonstrate the value of this integrated approach, connecting fundamental discoveries about muscle function with insights into insulin resistance and the benefits of exercise in people with Type 2 diabetes. This work is advancing our understanding of diabetes and helping lay the foundation for future approaches to prevention and treatment.”

Could Targeting Miro1 Lead to New Diabetes Therapies?

Although the results are encouraging, scientists still need to establish whether directly targeting Miro1 can produce safe and effective treatments for people with Type 2 diabetes. The restoration of insulin responsiveness was demonstrated in preclinical models, while the human trial showed that exercise reduced Miro1 levels alongside improvements in insulin sensitivity.

Kirwan plans to continue investigating these findings at the Harold Hamm Diabetes Center. His research will combine laboratory experiments with studies involving people to uncover more of the biological mechanisms responsible for diabetes and explore new strategies for preventing and treating the condition.

“Type 2 diabetes is an affliction in Oklahoma and nationally,” he said. “Ultimately, we are looking for cures, and we hope these recent findings could be part of the solution.”

The study received funding from the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute on Aging, the National Center for Complementary and Integrative Health, the National Heart, Lung, and Blood Institute, and the National Institute of General Medical Sciences.

Scientists from McGill University and the Centro de Investigaciones Paleontológicas (CIP) identified this unusual pattern while studying fossils from Colombia’s Paja Formation. The ancient marine ecosystem preserves an exceptional mixture of surviving Jurassic lineages and emerging Cretaceous groups, offering a rare glimpse into a period of profound biological change.

Drawing on these findings, McGill biology professor Hans Larsson and PhD graduate Dirley Cortés have proposed a new concept called a “Biotic Inflection.” The term describes an evolutionary turning point when older groups nearing extinction coexist with newer lineages that are beginning to expand and diversify.

A Perfect Storm for Ancient Ocean Biodiversity

The researchers believe an unusual combination of environmental conditions helped make this remarkable coexistence possible. Warm greenhouse temperatures, elevated sea levels, and coastal waters rich in nutrients may have supported an unusually diverse range of marine life.

Another important factor was the emergence of new ocean connections between the eastern Pacific and the early Atlantic through the region that is now Colombia. Together, these conditions likely created opportunities for different groups of animals to thrive within the same ecosystem. Many of these environmental influences continue to shape biodiversity around the world today.

“The Paja Formation records an extraordinary process in the history of life, when a ‘perfect storm’ of environmental factors we know to promote ecological complexity coincided with ancient lineages that were about to disappear. At the same time, new groups were beginning to flourish,” Larsson said.

A Lost World of Giant Marine Reptiles and Predators

The evidence comes from the Early Cretaceous Paja Formation near Villa de Leyva, Colombia. This fossil-rich region has preserved an astonishing variety of prehistoric marine animals, providing scientists with an unusually detailed picture of an ancient ocean ecosystem. Most of the fossils collected from the formation are housed at the CIP.

“This geological formation has produced an exceptionally rich fossil record that includes giant marine reptiles like long-necked plesiosaurs and marine crocodile relatives, as well as turtles, sharks, crustaceans and others,” Cortés explained. “Together, these animals formed the Paja Biota, one of the most ecologically complex marine communities found to date.”

In a previous study, the researchers reconstructed the feeding relationships among animals in the Paja Biota. Their analysis revealed an exceptionally intricate food web, with an unusually large variety of apex predators occupying the highest levels of the ecosystem.

This remarkable complexity makes the Paja Formation especially valuable for investigating how ecosystems change as older evolutionary groups decline and new ones become established.

Could This Discovery Change How Scientists Understand Evolution?

The proposed Biotic Inflection offers a potentially important new way to understand major changes in Earth’s biodiversity. Rather than being driven by a mass extinction, some evolutionary transitions may involve periods of extraordinary diversity, when declining lineages and emerging groups coexist.

However, the researchers emphasize that more evidence is needed to establish how common this pattern may have been. Additional fossil discoveries, more accurate estimates of fossil ages, and comparisons with geological formations in other parts of the world will help determine whether similar transitions occurred elsewhere in Earth’s history.

“I think we’ve discovered a new model of global biodiversity change. Now we’ll need to see just how widespread this could be in Earth’s history and how we can quantify its impacts,” Larsson said.

The research received funding from the Natural Sciences and Engineering Research Council of Canada, the Smithsonian Tropical Research Institute, the Anders Foundation, the 1923 Fund, Gregory D. and Jennifer Walston Johnson, the Fonds de recherche Nature et technologies Québec, and the McGill Biology Department Writing-Year Award 2024-2025.

But position and time are different. Heisenberg’s uncertainty principle does not impose the same restriction on these quantities. Now, researchers have experimentally demonstrated another fundamental limitation: an electron’s location and its behavior over time cannot both be determined with arbitrary precision. Known as the “space-time limit,” this newly observed relationship could have major implications for the future of quantum technology and ultrafast electronics.

The discovery comes from an international collaboration involving research groups at the Regensburg Center for Ultrafast Nanoscopy (RUN), led by Profs. Jascha Repp, Rupert Huber, Franz Giessibl, and Klaus Richter, along with a team at the Max Planck Institute in Hamburg led by Angel Rubio.

Watching Electrons Move at Incredible Speeds

Understanding how matter behaves at the smallest scales is essential for developing the next generation of technology. Advances in clean energy, quantum computing, and powerful electronics for artificial intelligence all depend on knowing how chemical reactions unfold, how light interacts with materials, and how electrons travel through electronic devices.

However, even the sharpest microscopic photographs cannot reveal the full picture. Scientists also need to observe how these processes change over time, effectively creating slow-motion movies of events occurring at the atomic scale.

At RUN, researchers are developing ultrafast microscopes capable of recording the movements of electrons, atoms, and molecules with extraordinary precision in both space and time. About ten years ago, scientists in Regensburg used ultrafast scanning tunneling microscopy to resolve the movement of a single molecule across space and time for the first time.

Tracking individual electrons presents an even greater challenge. At these microscopic distances, electrons can move roughly a thousand times faster than atoms and molecules, with important changes taking place over just attoseconds.

To appreciate how extreme these scales are, consider that an atom is approximately ten million times smaller than a millimeter. An attosecond is one-billionth of a billionth of a second. The difference between an attosecond and a second is comparable to the difference between one second and the entire age of the universe.

Making these measurements is especially difficult because electrons do not behave like ordinary objects. Their motion follows the unusual laws of quantum mechanics rather than the familiar rules of classical physics.

Ultrafast Lasers Reveal Quantum Tunneling

To observe electron behavior at these extraordinary speeds, the researchers built a new laser system that provides much finer time resolution than earlier experiments. The system allows them to control and study the quantum motion of individual electrons directly.

In the experiments, carefully timed laser pulses drive electrons from an extremely sharp metal tip toward a silver surface. The distance they travel is only a few atomic diameters.

The researchers detect this movement by measuring the resulting electrical current. To determine exactly when the electrons move, they use two pulses of light separated by a precisely controlled interval.

Simon Maier, the lead author of the paper, explains: “By varying the time interval between the two laser pulses, we can directly observe how the electrons respond.”

This approach revealed clear evidence of electron motion occurring on attosecond timescales. It showed that the laser pulses could transfer electrons within these incredibly brief intervals while allowing scientists to observe the process as it happened.

What makes the result particularly remarkable is how the electrons travel. Instead of moving like conventional particles, they behave as quantum waves. This allows them to pass through an energy barrier separating the metal tip from the silver surface, even though classical physics predicts they should not have enough energy to cross it.

This phenomenon, known as quantum tunneling, is somewhat like an object passing through a solid wall without breaking or damaging it.

“Our measurement can be understood as a high-speed camera for the electron wave packets, since you can see at what point in time the tunneling process takes place,” explains Katharina Glöckl, a doctoral student and co-author of the publication.

A Surprising 500-Attosecond Delay

To understand the measurements more deeply, researchers working with Prof. Angel Rubio performed sophisticated quantum simulations of the electrons’ behavior near the “space-time limit.”

Their calculations closely reproduced the experimental findings and uncovered another remarkable detail. The electrons did not respond to the light field instantaneously. Instead, their motion lagged behind it by approximately 500 attoseconds.

At such extreme scales, several fundamental features of quantum physics become important simultaneously.

For example, the researchers found that the laser pulses could not be described entirely by treating light as a wave or entirely by treating it as individual particles called photons. Their effects displayed characteristics of both descriptions. This combination was essential for exploring electron behavior so close to the “space-time limit.”

The team also discovered that controlling electron motion over extremely short intervals changes how the electrons are distributed in space. Quantum mechanics describes these electrons using wave packets, which represent how their wave properties extend across different locations.

The relationship between the timing of electron motion and the spatial extent of these wave packets revealed the central limitation behind the discovery.

A Hidden Tradeoff Between Space and Time

Raffael Spachtholz, another co-author of the study, explains: “The more precisely we want to pin down the electron’s position in time, the more energy we need to provide. And as a result, the electron wave packet spreads out more spatially.”

In other words, improving the precision of an electron’s timing comes with a cost. The more tightly researchers define when its motion occurs, the more broadly its quantum wave packet spreads through space.

To examine this relationship experimentally, the team placed a single atom on the surface to confine the electron wave packets to an extremely small region immediately before the laser pulses arrived.

This setup allowed the scientists to directly measure the connection between the electrons’ spatial distribution and the timing of their motion.

Importantly, even when the electrons received substantial energy from the laser pulses, their wave packets remained sufficiently localized for microscopy with atomic spatial resolution and attosecond time resolution.

The findings provide experimental insight into a fundamental space-time constraint that scientists had previously only suspected. They also make it possible to systematically investigate how changes in electron motion over time affect the spatial structure of quantum wave functions.

Could Quantum Electronics Become Hundreds of Thousands of Times Faster?

Beyond revealing a new aspect of quantum behavior, the discovery could open the door to technologies that operate on timescales far beyond the capabilities of today’s electronics.

One especially promising possibility involves using precisely controlled electron wave packets to influence chemical reactions.

Transferring a single electron to a molecule represents the smallest possible transfer of electric charge. But when that electron is concentrated within an exceptionally small region of space and time, the resulting local peak current density can reach as much as 1 trillion amperes per square centimeter.

Such extreme conditions could give scientists new ways to control chemical bonds and observe how molecules change during reactions.

“In the future, we want to use such wave packets to specifically trigger chemical reactions and observe, on the relevant length and time scales, how chemical bonds can be broken or altered,” explains Prof. Jascha Repp enthusiastically.

The implications could extend well beyond chemistry. Greater control over electron motion may eventually help engineers develop electronic devices and quantum information systems that operate at speeds approaching the fundamental limits of electron dynamics.

“In the long term, the insights gained could also contribute to operating electronics and quantum information processing at the intrinsic speed limit of electron motion itself — hundreds of thousands of times faster than the currently dominant CMOS technology,” adds Prof. Rupert Huber.

That possibility remains a long term technological goal rather than an achievement demonstrated in the current experiments. Nevertheless, the findings provide a new foundation for exploring how electrons can be manipulated at the smallest distances and shortest timescales.

For Repp and Huber, the results suggest that the range of potential applications is extraordinarily broad. They believe that future advances in controlling electrons at the space-time limit may ultimately depend more on human creativity than on the constraints imposed by nature.

Researchers found that adults who consumed higher amounts of caffeinated coffee developed dementia at considerably lower rates than those who rarely or never drank it. The findings were based on follow-up periods extending as long as 43 years, offering a valuable look at how everyday drinking habits relate to brain health over time.

The strongest associations appeared among people who drank two to three cups of caffeinated coffee each day. Tea consumption was also linked to better cognitive outcomes, although the amount associated with the greatest benefit was somewhat lower.

Interestingly, decaffeinated coffee did not show the same benefits, raising questions about whether caffeine itself might help explain the connection.

Coffee Drinkers Showed Much Lower Dementia Rates

One of the most striking findings involved the difference in dementia rates between regular coffee drinkers and people who consumed little or no coffee.

Among U.S. adults who drank higher amounts of caffeinated coffee, researchers recorded 141 dementia cases annually for every 100,000 people. In comparison, the rate was 330 cases per 100,000 people each year among those who rarely or never drank caffeinated coffee.

Dementia is a general term for conditions that progressively interfere with memory, thinking, reasoning, and the ability to perform everyday activities. Alzheimer’s disease is its most common cause, although several other brain disorders can also lead to dementia.

While occasional forgetfulness can be a normal part of aging, dementia involves cognitive difficulties severe enough to disrupt daily life. Identifying lifestyle habits associated with lower dementia risk is therefore an important area of research, particularly as populations grow older.

The findings suggest that regular caffeinated coffee consumption may be one such habit. However, the results show an association rather than proving that coffee directly prevents dementia. Other differences between coffee drinkers and people who avoid coffee could also contribute to the observed results.

Coffee Was Also Linked to Better Cognitive Health

The potential benefits were not limited to diagnosed dementia. Participants who drank more caffeinated coffee were also less likely to report that their memory or thinking abilities had declined.

Researchers found that 7.8% of adults who consumed higher amounts of caffeinated coffee reported subjective cognitive decline, compared with 9.5% of those who rarely or never drank it.

Subjective cognitive decline refers to changes in memory or thinking that people notice themselves, even when those difficulties have not necessarily been confirmed by formal cognitive testing. Someone experiencing it might feel that remembering information, concentrating, or finding the right words has become more difficult.

Such complaints do not automatically indicate dementia. Nevertheless, they can provide useful information about how people perceive changes in their cognitive abilities as they grow older.

The lower percentage among caffeinated coffee drinkers adds to the evidence linking coffee consumption with healthier cognitive aging.

How Much Coffee Offers the Greatest Benefit?

The researchers also examined whether the amount of coffee consumed was related to the strength of the observed benefits.

Drinking two to three cups of caffeinated coffee per day was associated with the most favorable outcomes for dementia risk and cognitive functioning.

Notably, this association remained apparent regardless of participants’ genetic risk of developing dementia. In other words, the relationship between coffee consumption and brain health was observed even among people whose inherited characteristics might make them more vulnerable to the disease.

Genetic risk refers to the influence of inherited variations in DNA that can increase or decrease a person’s likelihood of developing certain conditions. Although genetics can play an important role in dementia, they are only one part of a much larger picture that includes age, general health, and lifestyle.

The results also suggest that drinking larger amounts of coffee is not necessarily better. Consumption beyond the range associated with the strongest benefits did not appear to provide additional protection.

Tea Drinkers May Benefit Too, but Decaf Was Different

Coffee was not the only beverage associated with better brain health. Researchers found that drinking tea was also linked to lower dementia risk and better cognitive functioning.

For tea, the strongest associations appeared among participants who consumed one to two cups per day. As with coffee, drinking more than this amount did not appear to produce further benefits.

However, the study did not distinguish between caffeinated and noncaffeinated tea. As a result, the findings cannot establish whether caffeine was responsible for the association observed among tea drinkers.

The results for coffee offered an additional clue. While regular caffeinated coffee was associated with lower dementia risk and better cognitive outcomes, decaffeinated coffee did not demonstrate the same benefits.

Caffeine is a naturally occurring stimulant found in coffee, tea, and several other plants. It acts on the central nervous system and is best known for temporarily increasing alertness and reducing feelings of tiredness.

Whether caffeine also contributes to better brain health over many years is a separate question. The difference between regular and decaffeinated coffee makes this possibility worth investigating, but it does not establish caffeine as the cause of the observed benefits.

Taken together, the findings suggest that moderate consumption of caffeinated coffee and tea may be associated with healthier brain aging. For coffee drinkers, two to three cups daily appeared to offer the strongest association, while one to two cups of tea showed the most favorable results among tea drinkers.

Although additional research is needed to determine whether these beverages directly influence dementia risk, the long-term findings offer encouraging news for people who already enjoy coffee or tea as part of their daily routine.