Also known as riboflavin, vitamin B2 cannot be produced by the body and must come from food sources such as dairy products, eggs, meat, and green vegetables. Once absorbed, the vitamin is converted into molecules that help protect cells from oxidative damage and support other important biological functions.

Scientists at the Rudolf Virchow Centre (RVZ) at Julius-Maximilians-Universität Würzburg (JMU) have now discovered that this protective effect may come with a serious drawback. Their findings show that vitamin B2 metabolism can also shield cancer cells from destruction.

“Vitamin B2 plays a crucial role in protecting cancer cells from ferroptosis, a special form of programmed cell death,” says PhD student Vera Skafar. She is part of the research team led by José Pedro Friedmann Angeli, Professor of Translational Cell Biology. The study was published in Nature Cell Biology.

How Vitamin B2 Helps Cancer Cells Survive

Programmed cell death is one of the body’s natural defense systems. It allows damaged or dangerous cells to die in a controlled way without triggering inflammation in nearby tissue. Ferroptosis is one type of this process and has been linked to cancer, neurodegenerative diseases, and other serious conditions.

Ferroptosis occurs when iron-driven damage to cell membranes overwhelms a cell’s antioxidant defenses. Cancer cells often avoid this fate by strengthening systems that protect them from oxidative stress.

The new study found that vitamin B2 metabolism plays an important role in these protective defenses. According to the researchers, this means that blocking riboflavin-related pathways could make tumors more vulnerable to ferroptosis and easier to destroy.

Researchers Test a Possible Cancer Therapy Strategy

A protein called FSP1 was central to the team’s investigation. The protein helps healthy cells avoid unwanted cell death, and vitamin B2 supports its activity.

Using genome editing and cancer cell models, the researchers found that cancer cells became much more sensitive to ferroptosis when vitamin B2 was limited.

The team believes this process could eventually be used as a cancer treatment by shutting down vitamin B2 metabolism in tumors and triggering cancer cell death. However, there is currently no inhibitor specifically designed for that purpose.

To explore the idea further, the researchers tested roseoflavin, a naturally occurring compound produced by bacteria that has a structure similar to vitamin B2.

Roseoflavin Successfully Triggered Ferroptosis

In laboratory experiments using cancer cell models, the researchers found that roseoflavin was able to trigger ferroptosis even at low concentrations.

“It turned out that roseoflavin triggers ferroptosis in low concentrations,” says the group leader, “our experiments show the feasibility of this concept.”

The findings suggest that targeting vitamin B2 metabolism could become a promising new approach for future cancer therapies based on ferroptosis.

Next, the RVZ research team plans to develop more effective inhibitors of vitamin B2 metabolism and test them in preclinical cancer models.

Potential Implications Beyond Cancer

Friedmann Angeli says the importance of ferroptosis extends beyond oncology.

“Ferroptosis is not only relevant to cancer. Increasing evidence suggests that it also contributes to pathological processes in neurodegenerative diseases and in tissue damage following organ transplantation or ischemia-reperfusion injury.”

Because of this, understanding how vitamin B2 metabolism influences ferroptosis could eventually help scientists better understand a wide range of diseases involving excessive or insufficient cell death.

The research was supported by the German Research Foundation (DFG) through the priority program “Ferroptosis: from Molecular Basics to Clinical applications” (SPP2306).

The work was also conducted as part of the DeciFerr (Deciphering and exploiting ferroptosis regulatory mechanism in cancer) project led by Professor Friedmann Angeli. Since May 2024, the project has received funding from the European Research Council (ERC) through an ERC Consolidator Grant worth nearly two million euros.

Tinnitus can range from mildly irritating to severely distressing. For some people, the nonstop noise creates anxiety and disrupts daily life. Researchers estimate that as many as 14% of people globally experience the condition, with many cases considered severe.

A team from Oregon Health & Science University and Anhui University in China studied mice and found that increasing serotonin levels in the brain also increased behaviors associated with tinnitus.

Serotonin and Tinnitus Connection

The findings could have important implications for people living with tinnitus, especially those taking antidepressants that affect serotonin levels, said co-senior author Laurence Trussell, Ph.D., professor of otolaryngology in the OHSU School of Medicine and a scientist at the OHSU Vollum Institute and Oregon Hearing Research Center.

“People with tinnitus should work with their prescribing physician to find a drug regimen that gives them a balance between relief of psychiatric symptoms like depression and anxiety, while minimizing the experience of tinnitus,” Trussell said. “This study highlights the importance of clinicians recognizing and validating patient reports of medication-associated increases in tinnitus.”

The medications discussed in the study include selective serotonin reuptake inhibitors, commonly known as SSRIs. These antidepressants are widely prescribed for moderate to severe depression and anxiety because they raise serotonin levels in the brain.

Researchers have long suspected serotonin played a role in tinnitus, but the exact mechanism remained unclear.

“We’ve suspected that serotonin was involved in tinnitus, but we didn’t really understand how,” said co-author Zheng-Quan Tang, Ph.D., of Anhui University in China. “Now, using mice, we’ve found a specific brain circuit involving serotonin that goes straight to the auditory system, and found that it can induce tinnitus-like effects. When we turned that circuit off, we were able to ameliorate the tinnitus significantly.

“This gives us a much clearer picture of what’s going on in the brain — and points toward new possibilities for treatment.”

Tang began the project while working as a postdoctoral scholar in Trussell’s laboratory.

Brain Circuit Linked to Ringing Ears

The new work builds on earlier research published in 2017.

In the latest study, scientists used optogenetics, a technique that uses fiber optics and light to activate specific brain cells. By targeting neurons that produce serotonin, the researchers were able to trigger activity in regions of the brain involved in hearing. They then measured how the mice responded using a modified auditory startle test.

“When you stimulate these serotonergic neurons, we can see that it stimulates activity in the auditory region in the brain,” Trussell said. “We also saw that animals then behaved as if they were hearing tinnitus. In other words, it’s producing symptoms that we would expect to be experienced as tinnitus in humans.”

According to the researchers, the findings match reports from some patients who say their tinnitus becomes more intense while taking serotonin-boosting medications such as SSRIs.

Future Tinnitus Treatments

“Our study suggests a delicate balance,” Trussell said. “It may be possible to develop cell- or brain region-specific drugs that steer the elevation of serotonin in some brain regions but not others. In that way, it may be possible to separate the beneficial and important effects of the antidepressant from the potentially harmful effects on hearing.”

Trussell’s research was supported by the National Institutes of Health through award RO1DC004450. The authors noted that the findings and conclusions are solely their responsibility and do not necessarily reflect the official views of the NIH.

Scientists have been exploring ways to remove or repair these harmful cells, but there has been a major obstacle. Researchers have struggled to reliably identify senescent cells hiding among healthy cells in living tissue.

DNA Aptamers Help Researchers Identify Senescent Cells

A team at Mayo Clinic now says it has found a promising new strategy. Writing in the journal Aging Cell, the researchers describe a technique that uses molecules called “aptamers” to tag senescent cells.

Aptamers are short strands of synthetic DNA that naturally fold into complex three dimensional shapes. Those shapes allow them to attach to specific proteins found on the surfaces of cells.

Working with mouse cells, the scientists screened more than 100 trillion random DNA sequences and identified several rare aptamers capable of binding to proteins associated with senescent cells. Once attached, the aptamers effectively flagged the cells for identification.

“This approach established the principle that aptamers are a technology that can be used to distinguish senescent cells from healthy ones,” says biochemist and molecular biologist Jim Maher, III, Ph.D., a principal investigator of the study. “Though this study is a first step, the results suggest the approach could eventually apply to human cells.”

A Chance Conversation Sparked the Discovery

The project began with an unexpected idea shared during a casual conversation between graduate students at Mayo Clinic.

Keenan Pearson, Ph.D. — who recently earned his degree from Mayo Clinic Graduate School of Biomedical Sciences — had been studying how aptamers might be used against brain cancer or neurodegenerative diseases while working with Dr. Maher.

Elsewhere on campus, Sarah Jachim, Ph.D., — who was also completing graduate research at the time — was studying aging and senescent cells in the laboratory of Nathan LeBrasseur, Ph.D.

The two students crossed paths during a scientific event and started discussing their thesis projects. Dr. Pearson began wondering whether aptamer technology could be adapted to recognize senescent cells.

“I thought the idea was a good one, but I didn’t know about the process of preparing senescent cells to test them, and that was Sarah’s expertise,” says Dr. Pearson, who became lead author of the publication.

Researchers Pursue a “Crazy” Idea

The students presented the idea to their mentors as well as researcher Darren Baker, Ph.D., whose work focuses on therapies targeting senescent cells.

Dr. Maher says the concept initially sounded “crazy,” but intriguing enough to investigate further. The mentors ultimately embraced the collaboration.

“We frankly loved that it was the students’ idea and a real synergy of two research areas,” says Dr. Maher.

The research advanced quickly. Early experiments produced encouraging findings sooner than expected, leading the team to bring in additional students from several labs.

Then-graduate students Brandon Wilbanks, Ph.D., Luis Prieto, Ph.D., and M.D.-Ph.D. student Caroline Doherty contributed specialized techniques, including advanced microscopy and analysis of a wider variety of tissue samples.

“It became encouraging to expend more effort,” Dr. Jachim says, “because we could tell it was a project that was going to succeed.”

New Clues About the Biology of Zombie Cells

The study may offer more than just a new way to identify senescent cells. It also uncovered information about the cells themselves.

“To date, there aren’t universal markers that characterize senescent cells,” says Dr. Maher. “Our study was set up to be open-ended about the target surface molecules on senescent cells. The beauty of this approach is that we let the aptamers choose the molecules to bind to.”

Several of the aptamers attached to a variation of fibronectin, a protein found on the surface of mouse cells. Researchers do not yet understand exactly how this fibronectin variant relates to senescence, but the finding could help scientists better define what makes senescent cells unique.

Future Potential for Aging and Disease Treatments

The researchers caution that additional studies will be needed before aptamers can reliably identify senescent cells in humans.

Still, the technology could eventually become much more than a detection tool. Scientists believe aptamers might one day carry therapies directly to senescent cells, allowing highly targeted treatment approaches.

Dr. Pearson says aptamers are also less expensive and more adaptable than traditional antibodies, which are commonly used to distinguish different types of cells.

“This project demonstrated a novel concept,” says Dr. Maher. “Future studies may extend the approach to applications related to senescent cells in human disease.”

The research was conducted at Karolinska Institutet as part of the Swedish Physical Activity and Fitness study (SPAF). Scientists followed several hundred randomly selected men and women in Sweden from ages 16 to 63, repeatedly measuring their fitness and strength over a span of 47 years.

The study was published in the Journal of Cachexia, Sarcopenia and Muscle.

Rare Long Term Fitness Data

Most previous studies on aging and physical performance relied on cross sectional comparisons between different age groups. In contrast, the SPAF project repeatedly tested the same individuals over decades, making it one of the few long running studies of its kind.

By tracking the same participants over time, researchers were able to build a much clearer picture of how the body changes through adulthood and aging.

Physical Decline Begins Around Age 35

The results showed that physical capacity starts decreasing as early as age 35, even among people with different training backgrounds. After that point, the decline continues gradually and becomes more pronounced with advancing age.

Researchers examined changes in fitness, muscular strength, and endurance, all of which followed a similar downward trend over time.

Still, the study also found important evidence that exercise remains highly beneficial at any age. Participants who became physically active during adulthood improved their physical capacity by 5-10 percent.

Exercise Still Makes a Difference

“It is never too late to start moving. Our study shows that physical activity can slow the decline in performance, even if it cannot completely stop it. Now we will look for the mechanisms behind why everyone reaches their peak performance at age 35 and why physical activity can slow performance loss but not completely halt it,” says Maria Westerståhl, lecturer at the Department of Laboratory Medicine and lead author of the study.

The researchers plan to continue following the participants as they age. Next year, the group will be tested again when participants reach 68 years old.

Scientists hope the ongoing work will help reveal how lifestyle habits, overall health, and biological processes influence the way physical performance changes across a lifetime.

Researchers led by the University of Liverpool uncovered strong evidence that traces of original organic molecules, including collagen, still exist inside dinosaur bones dating back roughly 66 million years. The discovery adds powerful new support to a controversial idea that has divided paleontologists for more than 30 years.

Preserved Collagen Found in Dinosaur Bone

The fossil at the center of the study is a 22-kilogram Edmontosaurus sacrum, part of the dinosaur’s hip region, recovered from South Dakota’s famous Hell Creek Formation. Edmontosaurus was a large duck-billed plant eater that lived alongside Tyrannosaurus rex near the end of the Cretaceous Period.

Using a combination of advanced laboratory methods, including protein sequencing and several forms of mass spectrometry, scientists detected remnants of collagen embedded within the fossilized bone. Collagen is the primary structural protein found in bone tissue and one of the hardest biomolecules to explain away as contamination when identified in this context.

Researchers from UCLA also identified hydroxyproline, an amino acid strongly associated with collagen in bone. According to the team, this represented an important confirmation that degraded collagen fragments were genuinely present inside the fossil.

Professor Steve Taylor, chair of the Mass Spectrometry Research Group at the University of Liverpool’s Department of Electrical Engineering & Electronics, said:

“This research shows beyond doubt that organic biomolecules, such as proteins like collagen, appear to be present in some fossils.”

“Our results have far-reaching implications. Firstly, it refutes the hypothesis that any organics found in fossils must result from contamination.”

A Debate That Has Divided Paleontology

Claims of preserved soft tissues and proteins in dinosaur fossils have sparked fierce debate since the early 2000s. Some scientists argued the reported materials were modern contamination or bacterial residue rather than authentic dinosaur molecules.

One of the most famous discoveries came in 2005, when paleontologist Mary Schweitzer and colleagues reported soft tissue structures inside a Tyrannosaurus rex fossil. Later studies identified possible collagen and blood vessel-like structures in additional dinosaur specimens, including hadrosaurs related to Edmontosaurus.

The new Edmontosaurus analysis stands out because researchers used multiple independent testing methods to examine the same fossil. By combining microscopy, chemical analysis, and protein sequencing, the team aimed to rule out contamination and strengthen the case that the molecules were original to the dinosaur itself.

The findings were published in Analytical Chemistry in 2025 under the title “Evidence for Endogenous Collagen in Edmontosaurus Fossil Bone.”

Why This Discovery Matters

If proteins can survive in fossils for tens of millions of years, scientists may gain an entirely new way to study extinct animals.

Tiny molecular traces could potentially reveal evolutionary relationships between dinosaur species that are difficult to identify from bones alone. Researchers may also learn more about dinosaur growth, aging, physiology, and disease.

Taylor noted that scientists may now need to revisit fossil samples collected over the past century. Cross-polarized light microscopy images taken decades ago could contain overlooked evidence of preserved collagen in ancient bones.

“These images may reveal intact patches of bone collagen, potentially offering a ready-made trove of fossil candidates for further protein analysis,” Taylor explained.

“This could unlock new insights into dinosaurs, for example revealing connections between dinosaur species that remain unknown.”

The Mystery of Molecular Survival

The discovery also raises a fascinating scientific question: how did these molecules survive for so long?

Proteins normally break down over time, especially across geological timescales. Yet some fossils appear capable of preserving microscopic biological structures under specific conditions.

Scientists are increasingly investigating whether mineral interactions inside bone may help shield fragments of collagen from complete decay. Recent studies exploring fossil biomolecules suggest that certain burial environments and microscopic bone structures may create stable conditions that slow chemical breakdown dramatically.

Edmontosaurus fossils are already famous for their exceptional preservation. Some specimens discovered over the last century retained detailed skin impressions and other soft tissue features, earning the nickname “dinosaur mummies.”

More recent paleontology research has continued uncovering surprisingly detailed soft tissue preservation in Edmontosaurus specimens, including evidence of fleshy structures and preserved skin anatomy.

Together, these discoveries are reshaping how scientists think about fossils. Instead of viewing them solely as stone replicas of ancient bones, researchers are beginning to see some fossils as possible molecular time capsules that still preserve traces of prehistoric biology millions of years later.

Now, researchers at Columbia University say they have finally uncovered the mechanism responsible. Their new study explains how carbon dioxide (CO₂) interacts with different wavelengths of light in ways that cool the upper atmosphere while warming the planet below.

“It explains a phenomenon that’s a fingerprint of climate change, has been known to occur for decades, and has not been understood,” says Robert Pincus, a research professor of ocean and climate physics at Lamont-Doherty Earth Observatory, which is part of the Columbia Climate School, and co-author of the study published in Nature Geoscience.

Why CO₂ Cools the Stratosphere

Near Earth’s surface, CO₂ traps heat that would otherwise escape into space, contributing to global warming. But conditions are very different higher up in the atmosphere.

In the stratosphere, the atmospheric layer stretching from about 11km to 50 km above Earth’s surface, CO₂ behaves more like a cooling system. The molecules absorb infrared energy rising from below and then release part of that energy back into space. As atmospheric CO₂ levels increase, the stratosphere becomes even more effective at shedding heat, causing temperatures there to drop.

Scientists first predicted this effect in the 1960s through climate models developed by climatologist Syukuro Manabe, whose work later earned a Nobel Prize. Since the mid-1980s, the stratosphere has cooled by about 2 degrees Celsius. Researchers estimate that this cooling is more than 10 times greater than it would have been without human generated CO₂ emissions.

Although scientists understood the broad idea behind stratospheric cooling, many of the detailed processes remained unresolved.

“The existing theory was incredibly insightful, but at the moment we lack a quantitative theory for CO₂-induced stratospheric cooling,” says Sean Cohen, a postdoctoral research scientist at Lamont-Doherty Earth Observatory, which is part of the Columbia Climate School, and the study’s lead author.

The “Goldilocks Zone” of Infrared Light

To solve the puzzle, Cohen worked with Pincus and Lorenzo Polvani, a geophysicist in Columbia Engineering’s Department of Applied Physics and Applied Mathematics. The team built mathematical models that identified the major processes driving stratospheric cooling. They repeatedly compared their calculations with climate simulations and observational data, refining the equations over several months until the models aligned with reality.

Their research pointed to a key factor: the way CO₂ molecules interact with infrared light, also known as longwave radiation.

Not all infrared wavelengths behave the same way in the atmosphere. The researchers found that some wavelengths are especially effective at promoting cooling. They described this highly efficient range as a “Goldilocks zone.” As CO₂ concentrations rise, this zone widens, increasing the atmosphere’s cooling efficiency.

“It’s those changes in efficiency that are going to ultimately be what’s driving stratospheric cooling,” says Cohen.

The researchers also examined the effects of ozone and water vapor. While both can influence heating and cooling processes in the atmosphere, their impact on stratospheric cooling turned out to be relatively small compared with CO₂.

How Stratospheric Cooling Strengthens Warming Below

The team’s equations successfully reproduced several known features of the atmosphere. They matched observations showing that cooling becomes stronger with altitude, with the greatest cooling occurring near the top of the stratosphere. The calculations also confirmed that every doubling of CO₂ leads to about 8 degrees Celsius of cooling at the stratopause, the upper boundary of the stratosphere.

The study also highlights an important climate feedback. Although increased CO₂ helps the stratosphere radiate heat more effectively, the resulting cooler temperatures mean the Earth system ultimately releases less infrared energy into space overall. That strengthens heat retention closer to the surface, intensifying warming in the lower atmosphere.

“Here’s this process that we’ve known about for 50-plus years, and we had a pretty decent qualitative understanding of how it worked. However, we didn’t understand the details of what actually drove that process mechanistically,” says Cohen.

According to Cohen and Pincus, the research is less about proving climate change exists and more about improving scientific understanding of how the atmosphere works.

“This is really telling us what is essential,” says Pincus.

The findings could also have applications beyond Earth. Researchers say the same principles may help scientists better understand the atmospheres of other planets and distant exoplanets.

“Maybe we can better understand what’s going on in the stratospheres of other planets in our solar system or exoplanets,” says Cohen.

Some of these eruptions produce solar proton events (SPEs), during which charged particles race toward Earth at speeds reaching 90% of the speed of light. In 1972, several SPEs erupted between the Apollo 16 and Apollo 17 Moon missions. If astronauts had been exposed during a lunar mission, they could have faced lethal radiation levels. As space agencies prepare for future Moon exploration, scientists are working to better understand these unpredictable solar events.

Researchers at the Okinawa Institute of Science and Technology (OIST) have now developed a new way to uncover evidence of past SPEs. The team combined medieval historical records with ultra precise carbon 14 measurements taken from buried asunaro trees in northern Japan. Using this method, they identified a solar proton event that likely occurred sometime between the winter of 1200 CE and the spring of 1201 CE, a period marked by unusually intense solar activity. The findings were published in the Proceedings of the Japan Academy, Series B.

Professor Hiroko Miyahara from the OIST Solar-Terrestrial Environment and Climate Unit explained: “Previous studies on historical SPEs have focused on rare, extremely powerful events. Our paper provides a basis for detecting sub-extreme SPEs — events that occur more frequently and are around 10-30% of the size of the most extreme cases, but still hazardous. Sub-extreme SPEs are more challenging to detect, but our method now allows us to efficiently identify them and better understand the conditions under which they are more likely to occur.”

Ancient Trees Preserve Clues About Solar Storms

Earth’s magnetic field blocks most high energy particles released during SPEs. Near the poles, however, magnetic field lines open into space, allowing some particles to enter the atmosphere. During especially powerful events, these particles collide with atmospheric gases and create carbon 14 compounds that spread around the globe and become trapped inside living organisms.

By analyzing carbon 14 levels in preserved organic material such as ancient buried trees, scientists can track changes in solar activity stretching back thousands of years. The OIST team used an ultra precise measurement technique they spent more than a decade refining. This method can detect much smaller carbon 14 fluctuations than conventional techniques, making it possible to identify weaker “sub-extreme” solar proton events that were previously invisible.

Because the carbon 14 analysis is extremely time intensive, the researchers first needed clues about when unusual solar activity may have occurred.

Medieval Japanese Diary Revealed “Red Lights” in the Sky

One of the key clues came from Meigetsuki, the diary of the Japanese poet and courtier Fujiwara no Teika (1162-1241). In February 1204 CE, he described seeing “red lights in the northern sky over Kyoto.”

Solar proton events do not directly create auroras, but they are often linked with the same kinds of solar disturbances that do. That historical observation gave researchers a timeframe to investigate more closely.

The scientists then measured carbon 14 levels in buried asunaro wood recovered from Aomori Prefecture in northern Japan. They discovered spikes in carbon 14 that pointed to a sub-extreme solar proton event. By combining those measurements with dendroclimatic studies — that is, a dating method based on comparing patterns of tree-ring growth associated with regional climate — the researchers determined that the event likely occurred sometime between the winter of 1200 CE and the spring of 1201 CE. Historical records from China also described a red aurora visible at unusually low latitudes during that same period.

Evidence of an Exceptionally Active Sun

“The high-precision data not only allowed us to accurately date sub-extreme solar proton events, but it also lets us clearly reconstruct the solar cycles of the period,” said Miyahara. “Today, the Sun’s activity fluctuates over eleven-year-long cycles, but we’ve found that the cycle was just seven to eight years long back then, indicating a very active Sun. The SPE we have dated occurred at the peak of one of these cycles.”

The research helps fill important gaps in the history of solar activity and improves scientists’ understanding of dangerous space weather events. According to Miyahara, carbon 14 analysis alone is not enough. Historical records and other scientific methods are also essential for reconstructing past solar behavior.

“Historical literature provides a candidate time window, and dendroclimatology enables direct intercomparison between detected SPE and reports of sunspots and auroras recorded in literature. Integrated approaches like these are necessary to accurately reconstruct past solar activity, helping us better understand the characteristics of extreme space weather,” concluded Miyahara. “For example, while the SPE we found occurred near the peak of the solar cycle, some of the prolonged low-latitude aurora recorded in the literature seems to fall near the minimum of our reconstructed solar cycle. This is unexpected, and we’re excited to look further into what solar conditions could cause this.”

But a major genetic analysis from researchers at RIKEN’s Center for Integrative Medical Sciences suggests the picture is far more complicated.

Using whole-genome sequencing on more than 3,200 people from across Japan, the team found evidence supporting a third ancestral group tied to northeastern Asia and possibly linked to the ancient Emishi people. The findings, published in Science Advances, add powerful support to the increasingly discussed “tripartite origins” theory of Japanese ancestry.

The results also revealed something else surprising: Japan’s population is genetically more diverse than many researchers once assumed.

“The Japanese population isn’t as genetically homogenous as everyone thinks,” said Chikashi Terao, who led the study at RIKEN. “Our analysis revealed Japan’s subpopulation structure on a fine scale, which is very beautifully classified according to geographical locations in the country.”

A Massive DNA Map of Japan

To investigate Japan’s deep genetic history, researchers analyzed DNA samples collected from seven regions stretching from Hokkaido in the north to Okinawa in the south. The project became one of the largest whole-genome studies ever conducted on a non-European population.

Instead of relying on older DNA microarray methods, the team used whole-genome sequencing, which reads nearly all three billion DNA base pairs in a person’s genome. According to the researchers, this provides roughly 3,000 times more information than traditional techniques.

“Whole-genome sequencing gives us the chance to look at more data, which helps us find more interesting things,” Terao explained.

The scientists then combined the genetic information with medical histories, disease diagnoses, family histories, and clinical test results to build a large database known as the Japanese Encyclopedia of Whole-Genome/Exome Sequencing Library (JEWEL).

One especially important focus involved rare genetic variants. These uncommon DNA changes can sometimes preserve clues about ancient migration patterns and long-lost ancestral populations.

“We reasoned that rare variants can sometimes be traced back to specific ancestral populations, and could be informative in revealing fine-scale migration patterns within Japan,” Terao said.

The Hidden Third Ancestor

The analysis uncovered striking regional differences across Japan.

Jomon ancestry appeared strongest in Okinawa, where it was found in 28.5% of samples, while western Japan showed much lower levels at 13.4%. Researchers found that people in western Japan had stronger genetic connections to Han Chinese populations, likely reflecting major migration waves from continental East Asia between 250 and 794 CE. Those migrations also coincided with the spread of Chinese-style government systems, writing, and education throughout Japan.

The newly identified Emishi-related ancestry was concentrated in northeastern Japan and became less common farther west.

The findings build on earlier ancient DNA studies published in 2021 that first proposed the idea that modern Japanese people descend from three major ancestral sources instead of two. Those studies suggested that a third migration connected to the Kofun period played a major role in shaping modern Japan.

Recent follow-up studies have continued strengthening that idea. Researchers analyzing ancient genomes and skeletal remains have found increasing evidence that multiple migration waves entered Japan over centuries, creating a much more layered population history than previously believed.

Ancient Neanderthal and Denisovan DNA Still Affects People Today

The study also explored genetic material inherited from Neanderthals and Denisovans, two ancient human groups that interbred with Homo sapiens tens of thousands of years ago.

Scientists have become increasingly interested in why some of these ancient DNA fragments survived in modern humans while others disappeared. In many cases, the inherited genes appear linked to health, adaptation, or disease risk.

For example, earlier studies showed that Tibetans inherited a Denisovan-related version of the EPAS1 gene that may have helped humans survive in high-altitude environments. Researchers also previously identified Neanderthal-derived DNA associated with severe Covid-19 complications in some populations.

The Japanese genome study identified 44 archaic DNA regions still present in modern Japanese populations, many of them unique to East Asians. One Denisovan-derived region inside the NKX6-1 gene was associated with type 2 diabetes and may influence how some patients respond to semaglutide treatments.

Researchers also found 11 Neanderthal-derived genetic segments connected to conditions including coronary artery disease, prostate cancer, and rheumatoid arthritis.

Toward Personalized Medicine

Beyond tracing ancestry, the researchers believe the work could eventually improve healthcare.

The team identified potentially harmful variants in the PTPRD gene that may be linked to hypertension, kidney failure, and myocardial infarction. They also found common loss-of-function variants in the GJB2 and ABCC2 genes, which are associated with hearing loss and chronic liver disease.

“What we’ve tried to do is to find and catalog loss-of-function gene variants that are very specific to Japanese people, and to understand why they are more likely to have some specific traits and diseases,” Terao said. “We’d like to connect population differences with differences in genetics.”

The study reflects a broader shift happening in genetics research. For years, most large genomic databases heavily focused on people of European ancestry, limiting scientists’ understanding of disease risk in other populations.

Terao hopes expanding JEWEL with more Asian genomic data will help change that.

“It’s quite important to expand this to the Asian population so that in the long run, the results can benefit us too,” he said.