A new study led by researchers at the Texas A&M College of Veterinary Medicine and Biomedical Sciences (VMBS) found that excess RNA produced during poxvirus infections can impair mitochondria, the tiny structures responsible for generating most of the energy cells need to survive.

Published in Proceedings of the National Academy of Sciences, the research reveals an unexpected connection between RNA buildup and cellular energy production. The findings could have implications far beyond viral infections, potentially helping scientists better understand aging-related diseases and improve RNA-based medical treatments, including mRNA vaccines.

“Scientists have long known that RNA degradation helps control protein production and remove defective RNA,” said Dr. Zhilong Yang, a professor in VMBS’ Department of Veterinary Pathobiology. “Our study reveals another important role: it helps cells maintain the energy they need to function properly.”

Cells constantly produce and break down RNA as part of their normal activities. This cleanup process, known as RNA degradation, helps regulate protein production, eliminate faulty RNA, and control immune responses. The new findings suggest it also performs another essential function by protecting the cell’s energy supply.

Why Too Much RNA Can Damage Cells

RNA plays several important roles in keeping cells functioning. Messenger RNA (mRNA), for example, carries genetic instructions that tell cells which proteins to produce. These proteins are needed for nearly everything cells do, from maintaining their structure to carrying out essential chemical reactions.

Another type, double-stranded RNA (dsRNA), frequently appears during viral infections. Its presence can serve as a warning signal, alerting the immune system that a virus may have entered the cell.

Viruses often generate large quantities of RNA as they reproduce inside infected cells. Ordinarily, cellular cleanup systems help prevent RNA from accumulating to harmful levels. However, when RNA production exceeds the cell’s ability to break it down, the excess material can interfere with mitochondria and reduce energy production.

Scientists already understood that excessive double-stranded RNA could provoke potentially harmful immune responses. What surprised the researchers was discovering that too much ordinary messenger RNA could also damage mitochondria.

“MRNA is a normal component of our cells, but it seems like with many good things, if we get too much, that can become a problem for the cell,” Yang said. “When too much RNA builds up, including mRNA, it can damage the mitochondria and interfere with the cell’s ability to produce energy.”

This creates an unusual challenge for viruses. Although viruses depend entirely on the cells they infect to supply energy and manufacture proteins, producing excessive amounts of viral RNA can damage the very machinery they need to reproduce.

According to Yang, poxviruses, a group that includes the viruses responsible for smallpox and mpox, appear to have ways of managing this problem. They use RNA cleanup mechanisms to remove excess RNA, helping infected cells remain functional long enough for viral replication to continue.

“If the cell is not healthy, the virus would not replicate well,” Yang said. “The virus needs to keep RNA levels balanced inside the cell.”

Scientists Discover RNA Can Directly Damage Mitochondria

One of the study’s most unexpected findings emerged when researchers investigated exactly how excess RNA affects mitochondria.

Initially, the team suspected that RNA buildup was damaging these cellular powerhouses indirectly by activating the immune system. Certain types of RNA are known to trigger defensive responses, which can place additional stress on infected cells.

However, experiments revealed that the damage did not require an immune response.

“When we isolated only the mitochondria and added RNA, we still saw mitochondrial damage,” said Dr. Djamal Brahim Belhaouari, the study’s first author. “That was the moment we realized this could be a previously unknown cellular response to RNA.”

The researchers also observed that mitochondrial problems developed before substantial immune activation occurred. Furthermore, the damage did not depend on the immune pathways normally activated during infection.

Together, these results indicate that excess RNA itself can interfere with mitochondrial function, rather than simply causing damage through the body’s response to a virus.

The precise mechanism remains unclear, but the researchers have proposed a possible explanation involving electrical charges.

Mitochondria produce energy by maintaining an electrical and chemical difference across their inner membranes. This difference helps drive the production of ATP, the molecule cells use as their primary energy source.

RNA carries a negative electrical charge. The researchers suspect that when unusually large amounts accumulate near mitochondria, they may disturb the electrical conditions required for efficient energy production.

“We think the negatively charged RNA may accumulate around mitochondria and disrupt the electrical balance needed for energy production, although how it happens is unknown,” Yang said. “This is a new concept that we are continuing to explore.”

What the Discovery Could Mean for Aging and Disease

Although the experiments focused on viral infections, the findings raise questions about whether RNA buildup might contribute to other health problems.

Abnormal RNA accumulation has been observed in several conditions, including certain cancers, neurodegenerative diseases, and disorders associated with aging. Neurodegenerative diseases involve the progressive deterioration of nerve cells, as occurs in conditions such as Alzheimer’s and Parkinson’s disease.

Because mitochondria are essential for maintaining healthy cells, disruptions to their energy production could potentially contribute to cellular dysfunction in some of these conditions.

The researchers suggest that excess RNA may represent one previously unrecognized source of mitochondrial stress. However, further studies are needed to determine how broadly this mechanism operates and whether it directly contributes to these diseases.

“We think this has quite broad translational implications,” Brahim Belhaouari said. “Too much double-stranded RNA or mRNA that cannot be degraded effectively may contribute to disease processes in some contexts.”

Potential Implications for mRNA Vaccines and Future Treatments

The discovery could also provide useful information for scientists developing medicines that rely on RNA.

RNA-based therapies, including mRNA vaccines, work by introducing RNA instructions into cells to produce specific proteins. Understanding how cells respond to RNA, process it, and eventually break it down is important for designing these treatments.

By identifying another way excessive RNA can affect cellular health, the findings may help researchers optimize future RNA-based therapies and vaccines. The study does not establish that existing mRNA vaccines cause mitochondrial damage in people.

“Understanding this mechanism could help researchers design and optimize future RNA-based therapeutics and vaccines by better understanding how cells respond to large amounts of RNA,” Yang said.

More broadly, the research suggests that controlling RNA levels is important for more than maintaining accurate protein production or managing immune activity. It may also be essential for keeping mitochondria functioning and ensuring cells have enough energy.

For the scientists, the most striking result was that even a molecule cells depend on every day can become harmful when it accumulates beyond normal levels.

“Scientists already knew that too much double-stranded RNA can be harmful,” Yang said. “What surprised us was finding out that too much mRNA — something cells normally need every day — can also damage mitochondria and interfere with the cell’s ability to produce energy.”

Research reported in this study was supported, in part, by the National Institute of Allergy and Infectious Diseases (R01AI143709 to Z.Y.) and Texas A&M University. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Published in the journal PLOS One, the study found that adults aged 65 and older experienced meaningful improvements in physical performance after only 12 weeks. These gains are especially important because muscle strength and mobility influence the risk of falling, the ability to live independently, and overall health and longevity.

For older adults, being able to move comfortably and perform everyday activities is essential for maintaining quality of life. Simple tasks such as standing up from a chair, climbing stairs, and walking can become more difficult as strength and balance decline.

According to the Centers for Disease Control and Prevention, unintentional injuries, including those caused by falls, are among the leading causes of death in adults aged 65 and older.

Despite the importance of physical fitness, many older adults believe that meaningful improvements require long, demanding workouts. Christopher Sciamanna, professor of medicine and public health at Penn State College of Medicine and lead author of the study, says the new findings challenge that assumption. Even a brief daily routine can improve important measures of mobility and physical function.

“The human body is designed to improve very quickly,” Sciamanna said. “And just a few repetitions of an exercise performed regularly can lead to huge improvements. Exercise is about forward thinking — think about what you want to be able to do and train for it.”

Why Shorter Workouts Could Make Exercise Easier

Strength training, also known as resistance training, involves making muscles work against some form of resistance, such as body weight or elastic bands. Research has shown that it can substantially improve muscle strength within a few months.

However, fewer than one in five older adults meet the recommendation to perform muscle strengthening activities at least twice a week. Common obstacles include discomfort, limited time, and the physical demands of conventional exercise programs.

Another challenge is that planning an effective workout can feel overwhelming, particularly for people who are unfamiliar with exercise.

“Exercise is actually really complicated, because you have to decide how many repetitions, how far, how many sets, how much rest, and how many times per week,” said co-author Smita Dandekar, associate professor of pediatrics at Penn State College of Medicine. “It’s hard work, so there’s huge problems with people wanting to do exercise. If we can make it short, we’re part way there.”

The researchers had already seen encouraging results from an earlier experiment called FAST (Functional Activity Strength Training)-1. In that smaller study, 24 older adults performed just 30 seconds of push-ups and squats each day. After six months, their ability to perform squats had improved.

Other research has similarly suggested that performing only a few sets of exercises each week can produce strength improvements approaching those achieved with considerably longer workouts.

These findings led Sciamanna and his colleagues to investigate whether an especially brief exercise program could produce measurable improvements in older adults.

Testing a Simple Four-Minute Exercise Routine

For the new study, the Penn State researchers developed a program called FAST-2 to evaluate whether a short daily workout could improve mobility and physical ability in adults older than 65.

The trial included 97 participants whose average age was 74. They were randomly divided into two groups, with one following the exercise program and the other receiving no intervention.

Before the study began, participants reported exercising for an average of only about 18 minutes per week. That was far below the general recommendation of at least 150 minutes of moderate physical activity or 75 minutes of vigorous activity each week, Sciamanna explained.

The FAST-2 routine consisted of four simple movements:

• Push-ups: To strengthen muscles in the upper body.
• Chair stands: Repeatedly standing up from a seated position to work the legs.
• Two-arm rows: Pulling against resistance to strengthen the upper body.
• Stair stepping: Stepping up and down to challenge the legs and support functional mobility.

Each exercise lasted 30 seconds, followed by 30 seconds of rest, bringing the complete routine to four minutes.

Participants received four elastic resistance bands and an adjustable-height stepper, along with written instructions explaining how to perform each movement. The researchers also provided easier variations to accommodate different physical abilities.

For example, participants could perform push-ups against a wall or countertop rather than on the floor. Those who found chair stands challenging could use their hands on their knees for additional support.

As their strength improved, participants were encouraged to make the exercises progressively more difficult. Someone performing modified push-ups might advance to the standard movement, while another participant might increase the height of the stepper.

To evaluate the program, researchers measured how quickly and effectively participants could rise from a chair and how long they could balance on one leg. These assessments were conducted at the beginning, midpoint, and end of the 12-week study.

Such tests are valuable because they reflect movements people rely on throughout the day. Performance on these assessments can also help predict future mobility problems, fall risk, and the potential need for additional care.

Significant Strength and Balance Improvements in Just 12 Weeks

The results showed that the brief exercise program produced significant gains in physical function, even though it involved only 60 seconds of lower body resistance training per session.

Participants demonstrated several measurable improvements:

• 4.2 additional chair stands: An increase in the number of times participants could stand up from a chair within 30 seconds.
• 3.6 more seconds of balance: An improvement in how long participants could remain standing on one leg.
• 2.3 seconds faster: A reduction in the time needed to complete the sit-to-stand assessment.

These changes may seem modest, but they reflect physical abilities that are essential for everyday independence. Stronger legs and better balance can make activities such as getting out of a chair, climbing stairs, and walking easier to perform.

Sciamanna emphasized that these simple physical tests can reveal important information about a person’s future health and independence.

“These indicators predict your future ability to go into a nursing home, your future likelihood of falling and of developing difficulty walking,” Sciamanna said. “They give you a sense of whether or not you’re going to be able to be active in the future.”

Although the study measured improvements in physical performance rather than directly testing whether participants experienced fewer falls or avoided nursing home care, the findings suggest that short workouts could help preserve abilities closely tied to independent living.

A Workout Older Adults Can Actually Stick With

Beyond the improvements in strength and mobility, the researchers identified another major advantage of the four-minute routine: participants were able to follow it consistently.

Throughout the study, they completed their exercises on 81% of days.

That level of participation suggests that a short, straightforward workout may be easier to incorporate into daily life than a longer exercise program. It could also help people overcome obstacles such as limited time, discomfort, or difficulty maintaining a regular fitness routine.

For older adults who are largely inactive, even a small amount of consistent resistance training could therefore provide a practical starting point for improving physical function.

The researchers say their results reinforce the idea that exercise sessions do not need to be lengthy to produce meaningful benefits. By focusing on movements that support everyday activities, a few minutes of daily effort may help older adults maintain strength, mobility, and independence.

For Sciamanna, the ultimate purpose of exercise extends beyond simply becoming physically stronger. It is about preserving the ability to participate in life and continue doing the things that matter most.

“Exercise is the key to freedom,” he said. “Freedom is the ability to be able to do what you want to do, and I would say that if you can’t do what you want to do, you’re not free. I approach exercise by thinking of what I want to be able to do in 20 years, and then I train to do that.”

Study Authors and Research Contributors

Additional Penn State researchers involved in the study included Smita Dandekar of the Department of Pediatrics, Division of Hematology and Oncology at Penn State Health Children’s Hospital; Jordan Kurth, Liza S. Rovniak, Noel Ballentine, and Natalia Pierwola-Gawin of the Department of Medicine, Division of General Internal Medicine at Penn State College of Medicine; and Yimeng Shang and Shouhao Zhou of the Department of Public Health Sciences, Division of Biostatistics and Bioinformatics at Penn State College of Medicine.

Jonathan G. Stine also contributed to the research. He is affiliated with the Department of Medicine, Division of Gastroenterology and Hepatology at Penn State Health Milton S. Hershey Medical Center and holds an additional appointment in the Department of Public Health Sciences at Penn State College of Medicine.

Other contributors included Matthew Silvis of the Departments of Orthopedics and Rehabilitation and Family and Community Medicine at Penn State Health Milton S. Hershey Medical Center; Matthew A. Ladwig of Purdue University Northwest; David E. Conroy of the University of Michigan; Kathryn H. Schmitz of the University of Pittsburgh School of Medicine; and Margaret Danilovich of Northwestern University Feinberg School of Medicine.

The impact created what is now known as the Silverpit Crater, a massive structure buried deep beneath the seafloor. Although scientists first discovered it in 2002, its origins remained fiercely debated, with some researchers arguing that geological processes, rather than an object from space, were responsible.

A research team led by Dr. Uisdean Nicholson of Heriot-Watt University in Edinburgh has now provided the strongest evidence yet that Silverpit was formed by an asteroid or comet. By combining advanced seismic imaging, microscopic examination of rock samples, and computer simulations, the scientists have reconstructed the violent event and identified minerals that could only have formed under extraordinary pressure.

The findings, published in Nature Communications, establish Silverpit as one of the relatively few confirmed impact craters on Earth.

A Mysterious Crater Beneath the North Sea

The Silverpit Crater lies approximately 700 meters beneath the seabed in the southern North Sea, about 80 miles off the coast of Yorkshire, England. The crater itself measures roughly three kilometers across and is surrounded by a much larger, 20-kilometer-wide region of circular faults, which are fractures in the rock where movement has occurred.

When scientists first identified the formation in 2002, several features suggested that it had been created by a high-speed collision with an asteroid or comet.

Its nearly circular outline, elevated central peak, and surrounding rings of faults resembled structures found at other impact sites. Central peaks can develop when rocks compressed by a powerful collision rebound upward, somewhat like the way water rises in the center after an object splashes into a pool.

However, not everyone was convinced.

Some geologists proposed that the unusual formation resulted from the movement of underground salt deposits, which can deform the rock layers above them. Others suggested that volcanic activity had caused part of the seabed to collapse, producing a structure that only appeared to be an impact crater.

The disagreement persisted for years. In 2009, geologists even voted on the competing explanations, as documented in Geoscientist magazine. Most participants rejected the asteroid impact hypothesis.

The latest findings show that the impact explanation was correct.

Scientists Find the Smoking Gun for an Ancient Asteroid Impact

The breakthrough came from combining newly available seismic images with microscopic evidence recovered from beneath the seabed.

Seismic imaging allows geologists to investigate structures hidden underground by analyzing how sound waves travel through different layers of rock. This technique can reveal buried faults, craters, and other formations that cannot be observed directly.

Using the improved data, Nicholson and his colleagues were able to examine Silverpit’s internal structure in unprecedented detail.

But the most decisive evidence came from tiny mineral crystals discovered in rock cuttings collected from an oil well near the crater.

Dr. Uisdean Nicholson, a sedimentologist in Heriot-Watt University’s School of Energy, Geoscience, Infrastructure and Society, said: “New seismic imaging has given us an unprecedented look at the crater.

“Samples from an oil well in the area also revealed rare ‘shocked’ quartz and feldspar crystals at the same depth as the crater floor.

“We were exceptionally lucky to find these — a real ‘needle-in-a-haystack’ effort. These prove the impact crater hypothesis beyond doubt, because they have a fabric that can only be created by extreme shock pressures.”

Shocked minerals are particularly important because their internal crystal structures have been altered by immense pressure. Such changes can occur when an asteroid strikes at tremendous speed, generating powerful shock waves that pass through the surrounding rock.

Ordinary geological processes generally cannot produce these distinctive microscopic features. Their discovery at the same depth as the crater floor provides strong physical evidence that an extremely violent impact occurred.

A 160-Meter Asteroid Unleashed a Monster Tsunami

With the crater’s origins established, researchers used numerical models, or computer simulations based on physical laws, to reconstruct what happened during the collision.

Their results suggest that an asteroid approximately 160 meters across approached from the west and struck the seabed at a shallow angle.

Although much smaller than the asteroid associated with the extinction of the dinosaurs, an object of this size could still release an enormous amount of energy when traveling at cosmic speeds.

According to the simulations, the impact violently displaced vast quantities of rock and seawater, producing a towering curtain of debris before the material collapsed back into the ocean.

Dr. Nicholson said: “Our evidence shows that a 160-meter-wide asteroid hit the seabed at a low angle from the west.

“Within minutes, it created a 1.5-kilometer-high curtain of rock and water that then collapsed into the sea, creating a tsunami over 100 meters high.”

That means the collision sent material nearly a mile into the air before it fell back into the sea, generating a tsunami taller than a 30-story building.

Unlike ordinary wind-driven waves, tsunamis involve the movement of enormous volumes of water. They are typically generated when a sudden disturbance, such as an earthquake, underwater landslide, or asteroid impact, rapidly displaces the water above it.

The estimated height of Silverpit’s tsunami comes from computer modeling of the ancient impact rather than direct observation. Nevertheless, the reconstruction illustrates just how destructive even a relatively modest asteroid can be when it strikes the ocean.

A Scientific Debate Finally Settled After Decades

For Professor Gareth Collins of Imperial College London, the discovery brings a satisfying conclusion to a controversy he witnessed firsthand.

Collins participated in the 2009 debate over Silverpit’s origins and contributed the numerical simulations used in the new research.

Professor Collins said: “I always thought that the impact hypothesis was the simplest explanation and most consistent with the observations.

“It is very rewarding to have finally found the silver bullet. We can now get on with the exciting job of using the amazing new data to learn more about how impacts shape planets below the surface, which is really hard to do on other planets. “

The findings do more than settle an old argument. They also give scientists a valuable opportunity to study the underground damage caused by high-speed asteroid impacts.

Because much of Silverpit’s structure remains buried and well preserved, researchers can investigate how the collision fractured, displaced, and reshaped the surrounding geological layers.

These observations could help scientists interpret impact structures on other worlds, where the subsurface effects of collisions are often much more difficult to examine.

Why This Rare Asteroid Crater Matters

Earth has experienced countless asteroid and comet impacts throughout its history, but relatively few recognizable craters remain.

Weathering, erosion, sediment deposition, and plate tectonics continually reshape the planet’s surface. Over millions of years, these processes can wear down, bury, or completely destroy evidence of ancient collisions.

As a result, exceptionally preserved impact sites like Silverpit are scientifically valuable.

Dr. Nicholson said, “Silverpit is a rare and exceptionally preserved hypervelocity impact crater.

“These are rare because the Earth is such a dynamic planet — plate tectonics and erosion destroy almost all traces of most of these events.

“Around 200 confirmed impact craters exist on land, and only about 33 have been identified beneath the ocean.

“We can use these findings to understand how asteroid impacts shaped our planet throughout history, as well as predict what could happen should we have an asteroid collision in future.”

Hypervelocity impacts occur when objects strike at extremely high speeds, typically several kilometers per second. At those velocities, even an asteroid measuring only a few hundred meters across can deliver a devastating amount of energy.

With its origins now confirmed, Silverpit joins a small group of important underwater and buried impact structures, including the Chicxulub Crater in Mexico, associated with the mass extinction that wiped out the nonavian dinosaurs, and the Nadir Crater off the coast of West Africa, another recently confirmed asteroid impact site.

Together, these craters provide evidence of the powerful role cosmic collisions have played in shaping Earth’s geological and biological history.

By studying Silverpit’s remarkably preserved features, scientists hope to better understand what happens when an asteroid strikes the ocean, how the surrounding rock responds, and what such an event might mean for Earth in the future.

The research was funded by the Natural Environment Research Council (NERC).

Scientists at the University of British Columbia (UBC), working with colleagues at the University of Wisconsin-Madison, have identified a molecular mechanism that helps explain these complications. Their findings, published in Nature Communications, could guide the development of safer statins that maintain their cholesterol-lowering benefits while minimizing muscle damage.

How Statins Trigger a Harmful Calcium Leak

To investigate what happens inside muscle cells, the researchers used cryo-electron microscopy, an advanced imaging method that allows scientists to examine protein structures in remarkable detail. Their investigation centered on the ryanodine receptor (RyR1), a protein that regulates the movement of calcium within muscle cells.

Under normal conditions, this protein functions as a controlled gateway, releasing calcium when muscles need to contract. The researchers found that statins can interfere with this process by holding the channel open. As a result, calcium escapes continuously into areas where it should be carefully regulated, creating conditions that can injure muscle tissue.

“We were able to see, almost atom by atom, how statins latch onto this channel,” said lead author Dr. Steven Molinarolo, a postdoctoral researcher in UBC’s department of biochemistry and molecular biology. “That leak of calcium explains why some patients experience muscle pain or, in extreme cases, life-threatening complications.”

Three Statin Molecules Reveal the Mechanism Behind Muscle Damage

The researchers concentrated on atorvastatin, a commonly prescribed medication for lowering cholesterol. Although this particular drug was the main focus, their results suggest that similar interactions could occur with other medications in the statin family.

One of the most striking discoveries was the unusual way statin molecules attach to the calcium channel. Rather than acting individually, three molecules occupy a specific pocket within the protein. The first binds while the channel is closed, making it more likely to open. Two additional molecules then enter the pocket and hold the channel open, allowing calcium to continue leaking.

“This is the first time we’ve had a clear picture of how statins activate this channel,” said Dr. Filip Van Petegem, senior author and professor at UBC’s Life Sciences Institute. “It’s a big step forward because it gives us a roadmap for designing statins that don’t interact with muscle tissue.”

This detailed understanding could give drug developers a way to address the problem at its source. By modifying the specific features of statin molecules that interfere with muscle proteins, scientists may be able to reduce unwanted effects without compromising the drugs’ ability to control cholesterol.

A Potential Path Toward Safer Cholesterol Drugs

More than 200 million people worldwide use statins. Although severe muscle injury occurs in only a small percentage of patients, less serious problems such as soreness, weakness, and fatigue are considerably more widespread. These symptoms can be disruptive enough that some people discontinue their medication, potentially losing important protection against cardiovascular disease.

The discovery could eventually help researchers create treatments that are easier to tolerate, allowing more patients to continue taking medications that reduce their risk of heart attacks and strokes.

Achieving this level of understanding required exceptionally detailed imaging. Working with the high-resolution macromolecular cryo-electron microscopy facility at UBC’s faculty of medicine, the team was able to observe precisely how statin molecules interact with the muscle protein. These structural insights connect a longstanding drug safety concern to a specific molecular process, providing valuable information for future medication development.

“Statins have been a cornerstone of cardiovascular care for decades,” Dr. Van Petegem said. “Our goal is to make them even safer, so patients can benefit without fear of serious side effects.”

Although additional research and drug development will be needed before these findings translate into new treatments, they offer a promising direction. For millions of people who depend on statins to protect their hearts, future medications with fewer muscle-related complications could make treatment more comfortable and improve everyday quality of life.