Several factors appear to drive this decline, including accumulated cellular damage, changes in gene activity, chronic low-level inflammation, and shifts in the bone marrow environment. Even so, scientists have not fully understood how these different stresses combine to impair HSC function.

Investigating a Key Aging Pathway

To better understand this process, researchers from The University of Tokyo, Japan, and St. Jude Children’s Research Hospital, USA, explored how age-related stress affects HSCs. They focused on the receptor-interacting protein kinase 3 (RIPK3)-mixed lineage kinase like (MLKL) signaling axis, which is typically associated with necroptosis, a form of programmed cell death.

The study was led by Dr. Masayuki Yamashita, an Assistant Member at St. Jude Children’s Research Hospital, who, at the time of the investigation, was an Assistant Professor at The Institute of Medical Science, The University of Tokyo. Co-authors included Dr. Atsushi Iwama from The Institute of Medical Science, The University of Tokyo, and Dr. Yuta Yamada from St. Jude Children’s Research Hospital, who was a graduate student at The Institute of Medical Science, The University of Tokyo.

A Surprising Discovery About MLKL

The research began with an unexpected observation. Dr. Yamashita explains, “We discovered an unexpected phenotype in HSCs of MLKL-knockout mice repeatedly treated with 5-fluorouracil, where aging-associated functional changes were markedly attenuated despite no detectable difference in HSC death, prompting us to investigate whether this pathway might induce functional changes beyond cell death.”

This finding suggested that MLKL might influence stem cell aging without actually killing the cells. That idea became central to the study, which was published in Volume 17 of Nature Communications on April 6, 2026.

How Scientists Tested the Mechanism

To explore this possibility, the researchers used several types of genetically engineered mice, including wild-type, MLKL-deficient, and RIPK3-deficient models. They also used specialized reporter mice designed to detect MLKL activation using a Förster resonance energy transfer-based biosensor.

The mice were exposed to different stress conditions that mimic aging, such as inflammation, replication stress, and oncogenic stress. To measure how well HSCs functioned, the team relied mainly on bone marrow transplantation, which tests the ability of stem cells to rebuild the blood system.

Additional techniques provided deeper insights, including flow cytometry, ex vivo expansion, RNA-seq, assay for transposase-accessible chromatin-seq, high-resolution imaging, metabolic testing, and detailed studies of mitochondria. Together, these approaches allowed the researchers to examine how MLKL affects HSCs at multiple levels.

Mitochondrial Damage Without Cell Death

The results revealed a previously unknown role for MLKL in stem cell aging. Although MLKL is usually linked to cell death, its activation in HSCs did not increase cell death or reduce cell numbers. Instead, it acted in a different way.

When activated under stress, MLKL briefly moved to the mitochondria, the structures that generate energy within cells. There, it caused damage by lowering membrane potential, altering mitochondrial structure, and reducing energy production. These effects led to key features of aging in HSCs, including reduced ability to renew themselves, decreased production of lymphoid cells, and a shift toward myeloid cell output.

Blocking MLKL Preserves Stem Cell Function

When MLKL was removed or inactivated, many of these problems were significantly reduced. HSCs lacking MLKL retained their ability to regenerate, produced healthier immune cells, showed less DNA damage, and maintained better mitochondrial function. These benefits were seen even in older animals or under stressful conditions.

Notably, these improvements occurred without major changes in gene expression or chromatin accessibility. This suggests that MLKL influences aging through processes that occur after gene activity, particularly at the level of cellular structures like mitochondria, rather than through changes in DNA regulation or inflammation.

Implications for Aging and Future Therapies

The findings point to a common pathway that connects various types of cellular stress to mitochondrial damage and stem cell aging. By identifying MLKL as a key link in this process, the study offers new insight into how aging affects the blood system.

Dr. Yamashita emphasizes, “In the longer term, this research could lead to therapies that preserve the function of hematopoietic stem cells, ultimately improving recovery and long-term health for patients undergoing chemotherapy, radiation, or transplantation. By revealing how non-lethal activation of cell-death pathways drives stem cell aging, these findings may inspire new classes of mitochondrial-protective or necroptosis-modulating drugs.”

A New Understanding of Stem Cell Aging

Overall, the study reveals that MLKL plays an important role in stem cell aging without causing cell death. Instead, it responds to stress by damaging mitochondria and weakening HSC function over time. This discovery challenges traditional views of necroptosis-related proteins and opens new possibilities for slowing or preventing age-related decline in the blood and immune systems.

Inside a paleobiology lab lined with cabinets of ancient fossils, the Virginia Tech undergraduate held up a rough, pitted skull.

“This is a uniquely sucky specimen,” said Srivastava. “It’s so bad. Like, if you saw a human skull in this way, you’d throw up.”

Despite its poor condition, the senior geosciences major spent two years carefully reconstructing the fossil and figuring out where it fits in the evolutionary history of dinosaurs. His work, published in Papers in Palaeontology, offers new insight into how dinosaurs rose to dominance during the Jurassic period.

Although this kind of research is typically handled by experienced scientists, geobiologists Sterling Nesbitt and Michelle Stocker brought Srivastava onto the project as a first-year student.

“We want undergraduate researchers to experience the whole paleontological research process at Virginia Tech,” said Nesbitt. “Simba grabbed the project by the reins.”

Reconstructing a Rare Dinosaur Skull

The fossil had an unusual history. It was first discovered in 1982 by a team from the Carnegie Museum of Natural History at Ghost Ranch in New Mexico. More than 30 years later, Nesbitt rediscovered it in a drawer and brought it to Virginia Tech for further study.

Using computed tomography scanning data, Srivastava digitally separated the crushed bones and created a 3D printed reconstruction of the skull.

The fossil belonged to a carnivorous dinosaur species that lived more than three times earlier than Tyrannosaurus Rex.

These animals lived near the end of the Triassic period, which lasted from about 252 million to 201 million years ago. At that time, dinosaurs were not yet the dominant predators often seen in movies. They competed with early relatives of crocodiles and mammals for survival.

How Dinosaurs Rose to Power

That balance changed dramatically after a mass extinction event eliminated much of the competition. As the Triassic period ended, dinosaurs quickly became the dominant land animals.

“Dinosaurs go from being co-stars to the headliner,” Srivastava said.

Fossils from this critical transition are rare, especially well-preserved ones from the end of the Triassic. That makes this damaged skull especially valuable.

In fact, no other specimen like it has been found.

Even in its distorted state, the fossil revealed important details. The dinosaur had large cheekbones, a broad braincase, and likely a short, deep snout. These features had not been seen before in early dinosaurs, suggesting they were evolving in more complex ways than previously understood.

A New Species With a Strange Look

Srivastava named the new species based on its unusual appearance.

“We landed on Ptychotherates bucculentus, which means ‘folded hunter with full cheeks’ in Latin,” said Srivastava. “One paleo-artist said that it looked like a murder muppet.”

After years of analysis, the team determined that this dinosaur belonged to Herrerasauria, one of the earliest groups of carnivorous dinosaurs. It appears to have been among the last surviving members of this lineage.

Rethinking the End-Triassic Extinction

The fossil led to another unexpected conclusion.

Ptychotherates was found in rock layers that may date to just before the mass extinction at the end of the Triassic period, and no other members of its group have been found after that time, possibly suggesting that this dinosaur group went extinct as a result of that mass extinction.

“This forces us to reconsider the impact of the end-Triassic extinction as something that wiped out not just the competitors to dinosaurs, but some long-standing dinosaur lineages themselves,” Srivastava said.

Because no herrerasaurians have been discovered elsewhere from such a late point in the Triassic, scientists think the region that is now the American Southwest may have been their final refuge.

One Fossil, an Entire Lost Lineage

Srivastava’s “folded hunter” may be the only remaining evidence of this group’s final chapter.

“This specimen, it fits in my hands, but it is the only proof that any of these dinosaurs lived this long, lived in these latitudes, the only proof that they evolved to have this skull shape,” said Srivastava. “All these billions of individuals that existed through time are spoken for by this one specimen.”

Living in the eastern United States between 83 million and 76 million years ago, Deinosuchus schwimmeri was a school-bus-sized relative of modern alligators that preyed on dinosaurs. The animal could grow up to 31 feet (9.45 meters) long. A life-size replica of this ancient giant is now on display at the Tellus Science Museum in Cartersville, Georgia. The project reflects two years of collaboration between Schwimmer and Triebold Paleontology Inc., a company known for creating detailed fossil skeleton models for museums and institutions worldwide.

Museum Display Brings Prehistoric Ecosystem to Life

“Each year, we have thousands of students visit us from across Georgia and neighboring states,” the Tellus Science Museum’s director of education, Hannah Eisla, explained. “Many of these students come on school field trips specifically to learn more about the region they call home and how it has changed over time. The addition of Deinosuchus schwimmeri allows us to provide a more detailed picture of this area’s ecosystem in the Cretaceous Period.”

“Tellus is currently the only museum to have a cast of Deinosuchus schwimmeri, so this is an experience our visitors can’t get anywhere else,” added Rebecca Melsheimer, the museum’s curatorial coordinator. “The scale of the dinosaurs and other creatures that lived during [the Late Cretaceous epoch] is hard to capture in words or pictures. We can tell you that Deinosuchus is 30 feet long, but seeing it is far more impactful.”

Naming a New Species After Decades of Research

In 2020, a team of paleontologists officially identified and named the species Deinosuchus schwimmeri in recognition of Schwimmer’s extensive contributions to the field. Their study, published in the Journal of Vertebrate Paleontology in July 2020, noted that the name honored “his tireless work on the Late Cretaceous paleontology of the Southeast and Eastern Seaboard, USA.” This recognition followed years of detailed fossil analysis, scientific publications, conference presentations, and Schwimmer’s 2002 book on the genus.

For more than 40 years, Schwimmer has explored fossil sites across Alabama, Georgia and Texas in search of Deinosuchus remains. Supported in part by National Geographic grants, his work has uncovered important specimens that are now housed in major institutions such as the Smithsonian Institution in Washington, D.C., the American Museum of Natural History in New York, and the Tellus Science Museum.

Building a Life-Size Replica With Modern Technology

According to Schwimmer, creating a scientifically accurate, full-scale replica requires careful attention to detail. For this project, the Triebold Paleontology team used high-resolution 3D scans of fossil specimens to reconstruct the animal’s skeletal structure and armored skin features. The result is a highly detailed model that not only impresses visually but also contributes to scientific understanding.

“These replicas are more than just creating a ‘scare factor,'” Schwimmer explained. “Understanding dinosaurs’ predatory habits helps us decode some of nature’s greatest survival strategies. By studying these ancient apex predators, we are essentially looking back in time to see exactly how life adapted and dominated a changing world.”

A Lifelong Fascination With a Prehistoric Predator

Schwimmer’s interest in Deinosuchus began during his childhood in New York City, where he lived just 10 blocks from the American Museum of Natural History. A display featuring a large skull first captured his imagination. He later discovered his first Deinosuchus fossil in 1979, shortly after joining Columbus State (then Columbus College). Since then, his work has focused on reconstructing the animal’s biology and environment.

His research has made him a global expert on life during the Late Cretaceous epoch (100.5 million years ago to 66 million years ago) in the southeastern United States. Over the years, his studies have also helped identify several important fossil “firsts” in Georgia, including evidence of flying reptiles (pterodactyls), dinosaurs, and Deinosuchus itself.

Publications, Discoveries, and Scientific Impact

Schwimmer’s findings from his early research years were compiled in his 2002 book, “King of the Crocodylians: The Paleobiology of Deinosuchus.” The book gained wide attention, becoming an Amazon top-seller in its category and a popular selection among science-focused reading groups. He is currently working on an updated version.

His expertise has since been sought by major institutions such as Atlanta’s Fernbank Museum of Natural History, the University of Texas’ Vertebrate Paleontology Laboratory, and the Tellus Science Museum. These organizations have relied on his guidance for fossil interpretation and exhibit development.

In 2010, Schwimmer contributed to two notable studies related to Deinosuchus. One examined bite marks on dinosaur bones, while the other focused on fossilized dung (coprolites) studied by undergraduate Samantha (Harrell) Stanford under his supervision. Their work was published in the “New Mexico Museum of Natural History and Science Bulletin” and presented at the Geological Society of America Northeastern-Southeastern Annual Meeting.

Hands-On Research Opportunities for Students

Schwimmer emphasized that fields like paleontology and other Earth sciences offer valuable opportunities for students to participate in hands-on research close to home. Regional universities such as Columbus State allow students to work directly with faculty and gain field experience.

“[Harrell] came out in the field and collected fossils with me. At most universities, undergraduates rarely collaborate on or publish peer-reviewed research. Institutions of our size provide undergraduate students like Samantha with greater one-on-one access to faculty mentors and field-based research opportunities like this that, while local, are still quite impactful on the field,” Schwimmer said.

A Local Fossil Treasure and a Window Into the Past

With several Deinosuchus fossil sites located within 40 miles of Columbus, the surrounding region has proven especially rich for discoveries. Schwimmer noted that this proximity makes the Tellus Science Museum an ideal location for displaying one of the first full-scale replicas.

“Bones and fossils tell us only part of the story,” Schwimmer concluded. “Fully assembled, life-size replicas become a blueprint for better understanding the dynamic animals that creatures like Deinosuchus really were.”